abbot traninig report
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ABOUT US:Abbott Laboratories is a highly diversified global health care company devoted to the discovery, development, manufacture and marketing of pharmaceutical, nutritional and medical products, including devices and
diagnostics With over 70,000 employees worldwide and a global presence in more than 130 countries, Abbott is committed to improving people's lives by providing cost effective health care products and services that consistently meet the needs of our customers. Abbott Pakistan is part of the global healthcare corporation of Abbott Laboratories, Chicago, USA. Abbott started operations in Pakistan as a marketing affiliate in 1948; the company has steadily expanded to comprise a work force of over 1500 employees. Currently two manufacturing facilities located at Landhi and Korangi in Karachi continue to use innovative technology to produce top quality pharmaceutical products. Abbott Pakistan has leadership in the field of Pain Management, Anesthesia, Medical Nutrition, Anti-Infectives and Diagnostics. Our wide range of products is managed and marketed through four marketing arms. The Diagnostic Division operates from its office located at Korangi, Karachi. With leading products in several key segments of the diagnostic market, Sales and support staff are available in all the major cities of the country. A continuous process of innovation, research and development at Abbott's worldwide facilities enables Abbott Pakistan to offer effective solutions for various healthcare challenges, with products and services that are well focused, within the customer's reach and contribute to improved health care of the people of Pakistan.
PRODUCTS: Abbutol Abocain Abocal Abozole Abrifam Acyclovir Arinac
Artifen Atrelax Becefol Bejectal Bevidox Brufen Burnol Calcijex Cecon Cofcol Citro Soda Cremaffin Dayalets Daycor Dijex Dobutamine Enoxabid Entamizole Epival Erybron Erythrocin Eryderm Flexin Forane Froben Ganaton
Gopten Hytrin Iberet Isoptin Klaricid Lucrin Lincomycin Loftyl Mammol Moculator Mospel Neophage Nicor Optilets-M Pentothal Pramet - FA Prothaiden Protium Rambuzid Rashnil Reductil Rondec Savourane Selsun Silliver Somogel
Sparaxin Survanta Surbex Tarka Trividox Tronolane Urixin Vancomycin Vi-Daylin
INTERNSHIP COVER THE AREA
QUALITY CONTROL PRODUCTION
Q.C LABORATORYTHE LAB IS FURTHER DIVIDED INTO:
CONVENTIONAL LAB HPLC SECTION
Conventional lab: DISINTEGRATION TEST. DISSOLUTION TEST. WEIGHT UNIFORMATY TEST. FRIABILITY TEST. PHYSICAL TEST. MOISTURE ANALYZER. PH METER. OXIDIZABLE TEST. MELTING POINT. VISCOSITY TEST. SPECIFIC GRAVITY.
HPLC SECTION: HPLC GC ATOMIC ABSORPTION TEST.
DISINTEGRATION TEST:The disintegration test is performed to find out that within how much time the tablet disintegrates. The apparatus used for this test is known as disintegration apparatus. It consists of a glass or plastic tube which is open at one end and the other end is fitted with a rust proof no. 10 mesh sieve. About 6 tablets are placed in the tube along with a plastic disk over it, the tube is allowed to move up and down and the time of disintegration is noted when all the tablets have passed through the sieve.
The disintegration test is a measure of the time required under a given set of conditions for a group of tablets to disintegrate into particles which will pass through a 10 mesh screen. Generally, the test is useful as a quality assurance tool for conventional dosage forms. The disintegration test is carried out using the disintegration tester which consists of a basket rack holding 6 plastic tubes, open at the top and bottom, the bottom of the tube is covered by a 10-mesh screen. The basket is immersed in a bath of suitable liquid held at 37 o C, preferably in a 1L beaker. For compressed uncoated tablets, the testing fluid is usually water at 37 o C but some monographs direct that simulated gastric
fluid be used. If one or two tablets fail to disintegrate, the test is repeated using 12 tablets. For most uncoated tablets, the BP requires that the tablets disintegrate in 15minutes (although it varies for some uncoated tablets) while for coated tablets, up to 2hours may be required.
DISSOLUTION TEST:The apparatus used for this test is known as dissolution apparatus. For performing the test a suitable volume of dissolution medium like distilled water, HCl or phosphate buffer is filled in the glass vessel which is submerged in the water bath maintained at 370C.The motor is started and the mixer rotates then the tablet is introduced in the vessel The samples are withdrawn after specified interval and filtered immediately through a suitable filter medium .The samples are tested by UV spectroscopy for proportion of drug dissolved. Drug release in the human body can be measured in-vivo by measuring the plasma or urine concentrations in the subject concerned. However, there are certain obvious impracticalities involved in employing such techniques on a routine basis. These difficulties have led to the introduction of official in-vitro tests which are now rigorously and comprehensively defined in the respective Pharmacopoeia.
Tablet Dissolution is a standardized method for measuring the rate of drug release from a dosage form. The principle function of the dissolution test may be summarized as follows: Optimization of therapeutic effectiveness during product development and stability assessment. Routine assessment of production quality to ensure uniformity between production lots.
Assessment of bioequivalence, that is to say, production of the same biological availability from discrete batches of products from one or different manufacturers. Prediction of in-vivo availability, i.e. bioavailability (where applicable). Although initially developed for oral dosage forms, the role of the dissolution test has now been extended to drug release studies on various other forms such as topical and transdermal systems and suppositories.
APPARATUS: Baskets - including special polyurethane suppository baskets Paddles Shafts Paddle over Disc (USP Method 5) for Transdermal Delivery Systems Rotating Cylinder (USP Method 6) alternative for Transdermal Delivery Systems Special mini cell(vessel) and paddle for transdermal studies of topical preparations such as liquids, suspensions, gels and ointments
WEIGHT UNIFORMITY TEST:
For carrying out this test generally 10 tablets at random are taken and weighed. The average weight is calculated, the tablet is weighed individually and weight is noted. The weights of individual tablets are then compared with the average weight .This test is repeated after short intervals of time. The difference between the weight in tablets can lead to variation in dose. Therefore all the tablets of a batch must confirm to this test. For carrying out this test generally 20 tablets at random are taken and weighed. The average weight is calculated, then each tablet is weighed individually and weight noted. The weights of individual tablets are then compared with the average weight already calculated and see that not more than two tablets fall out side the range. The range is given in STM.
FIRABILITY TEST:A friable substance is any substance that can be reduced to fibers or finer particles by the action of comparatively little pressure or friction on its mass, such as inadvertently brushing up against the substance. The term could also apply to any material that exhibits these properties.
Friction and shock are the forces that most often cause tablets to chip, cap or break. The friability test is closely related to tablet hardness and is designed to evaluate the ability of the tablet to withstand abrasion in packaging, handling and shipping. It is usually measured by the use of the Roche friabilator. A number of tablets are weighed and placed in the apparatus where they are exposed to rolling and repeated shocks as they fall 6 inches in each turn within the apparatus. After four minutes of this treatment or 100 revolutions, the tablets are weighed and the weight compared with the initial weight. The loss due to abrasion is a measure of the tablet friability. The value is expressed as a percentage. A maximum weight loss of not more than 1% of the weight of the tablets being tested during the friability test is considered generally acceptable
and any broken or smashed tablets are not picked up. Normally, when capping occurs, friability values are not calculated. A thick tablet may have less tendency to cap whereas thin tablets of large diameter often show extensive capping, thus indicating that tablets with greater thickness have reduced internal stress
OXIDIZABLE SUBSTANCES:We take 100 ml sample in the conical flask, add 10 ml H2SO4 and some drops of potassium permanganate and then heat it to boil. If pink color remains it means that the oxidizable substances are not present, if disappears then it means that the oxidizable substances are present.
MOISTURE ANALYZER:VACUUM OVEN:The classic laboratory method of measuring high level moisture in solid or semi-solid materials is loss on drying (LOD). In this technique a sample of material is weighed, heated in an oven at 600C under vacuum for an appropriate period, cooled in the dry atmosphere of a desiccator, and then reweighed. If the volatile content of the solid is primarily water, the LOD technique gives a good measure of moisture content.
ELECTRONIC MOISTURE BALANCE:These analyzers incorporate an electronic balance with a sample tray and surrounding heating element. Under microprocessor control the sample can be heated rapidly and a result based on the moisture loss rate is obtained.
KARL FISCHER MOISTURE ANALYSER:Karl Fischer titration is a classic titration method that is used to determine trace amounts of water in a sample. It was invented in 1935 by the German chemist Karl Fischer. The reagent used in titration is methanol. WORKING PRINCIPLE: Water react stichiometrically with iodine, producing iodide. While there is still water present, the iodine is converted to iodide, which is colorless. Once all of the water has been reacted, the color of the iodine comes through.
ADVANTAGES OF KARL FISCHER MOISTURE ANALYSER: The popularity of the Karl Fischer titration is due in large part to several practical advantages that it holds over other methods of moisture determination, including:
High accuracy and precision Selectivity for water. Small sample quantities required. Short analysis duration. Suitability for analyzing solids, liquids, gases. Independence of presence of other volatiles. Suitability for automation.
ASCORBIC ACID:Vitamin C (ascorbic acid) is an antioxidant that is essential for human nutrition. Vitamin C deficiency can lead to a disease called scurvy, which is characterized by abnormalities in the bones and teeth. Many fruits and vegetables contain vitamin C, but cooking destroys the vitamin, so raw citrus fruits and their juices are the main source of ascorbic acid for most people. One way to determine the amount of vitamin C in food is to use a redox titration. The redox reaction is better than an acid-base titration since there are additional acids in a juice, but few of them interfere with the oxidation of ascorbic acid by iodine. Iodine is relatively insoluble, but this can be improved by complexing the iodine with iodide to form tri iodide: I2 + I- I3Tri iodide oxidizes vitamin C to form dehydro ascorbic acid: C6H8O6 + I3- + H2O --> C6H6O6 + 3I- + 2H+ As long as vitamin C is present in the solution, the tri iodide is converted to the iodide ion very quickly. However, when the all the vitamin C is oxidized, iodine and tri iodide will be present, which react with starch to form a blue-black complex. The blue-black color is the endpoint of the titration. This titration procedure is appropriate for testing the amount of vitamin C in vitamin C tablets, juices, and fresh, frozen, or packaged fruits and vegetables. The titration can be
performed using just iodine solution and not iodate, but the iodate solution is more stable and gives a more accurate result.
MELTING POINT TEST:
Melting point analysis is one of the simplest and most useful techniques for the identification of a chemical substance. A melting point is a characteristic physical property of a substance. If a chemist is in doubt as to the identity of what he or she has synthesized, the melting point of the unknown is measured and is compared to previously published melting points of "candidate" substances. Comparing the melting point of a newly synthesized substance to the known values of previously characterized compounds can help determine which of the suspected compounds has been made.
Melting point analysis can also provide information about the purity of a sample. A substance containing impurities usually melts at a lower temperature than the pure compound, and melts over a wide range of temperatures. In general, the smaller the range of melting temperatures, the higher the purity of the sample.
When a melting point analysis is performed, a small amount of sample is first loaded into a melting point capillary tube, which is then heated in a melting point apparatus until
melting is observed. A melting point capillary tube is a thin glass capillary pipet that has been sealed closed at one end. The sample needs to be packed at the closed end of the tube. There are a few technical tricks to doing this - see the interactive walk-through below. Once the sample is loaded and packed, you are ready to proceed with melting point determination by heating the sample in a melting point apparatus. A melting point apparatus is an electrical device equipped with a thermometer, a magnifying glass, and heating block with which a hole has been drilled to allow a melting point capillary tube to be inserted. Such devices can typically heat a sample to at least 500C. We use the optimelt (automatic melting point system) apparatus in our labs, as it can be loaded with three tubes at once. The melting point of a substance is the temperature at which the solid phase converts to the liquid phase under 1 atmosphere of pressure. The melting point is one of a number of physical properties of a substance that is useful for characterizing (describing) and identifying the substance. To measure the melting point of a substance, it is necessary somehow to gradually heat a small sample of the substance while monitoring its temperature with a thermometer. The temperature at which liquid is first seen is the lower end of the melting point range. The temperature at which the last solid disappears is the upper end of the melting point range. A pure substance normally has a melting point range no larger than 1-1.5 oC. Preparing a melting point capillary. A glass capillary tube is normally used to contain the sample for a melting point determination. Therefore the tube must have one open end into which the sample can be loaded, and one sealed end so that the capillary will retain the solid sample. Glass capillary tubes for holding the solid sample are commercially available.
VISCOSITY TEST:The viscosity is check by apparatus consist of a rod on which paddle are placed.the paddle circulate and viscosity is noted from screen.
POLAR METER:The polarized light passes through the sample tube and exhibits angular rotation to the left (-) or right (+). On the side opposite the polarizer is the analyzer. Using optics, visual fields are manually adjusted by the user to measure the optical rotation angle.
In an optical rotation angle polarimeter for investigating optical activity of a test object, a two-frequency laser source generates a laser beam with two eigen modes of two different temporal frequencies and two orthogonal linear polarized waves. The laser beam is to be passed through the test object. The polarized beam splitter is adapted to receive and split the laser beam, which exits the test object, into first and second orthogonal optical heterodyne interference X-axis and Y-axis components. Each of first and second photo detectors receives a respective one of the first and second orthogonal optical heterodyne interference X-axis and Y-axis components from the polarized beam splitter, and generates a corresponding optical heterodyne interference signal. A signal processor is connected to the first and second photo detectors, and combines the optical heterodyne interference signals therefrom so as to obtain an optical heterodyne interference output. An amplitude detector detects the amplitude of the optical heterodyne interference output, which serves as a measure of the optical activity of the test object. In addition, the laser beam has an adjustable wavelength to permit measurement of dispersion of optical rotation angles versus wavelength for an optically active material or substance.
The sample is placed in the glass rod which is present in polar meter. It check the purity because if there is impurity this will cause change in polarity.
SPECIFIC GRAVITY TEST:Specific gravity G is defined as the ratio of the weight of an equal volume of distilled water at that temperature both weights taken in air. Clean and dry the density bottle
Weigh the empty bottle with stopper (W1) Put distilled water in the bottle and again weigh it(W2). Again fill the bottle completely with sample put the stopper and weigh it(W3).
pH METERA pH meter is an electronic instrument used to measure the pH (acidity or alkalinity) of a liquid (though special probes are sometimes used to measure the pH of semi-solid substances). A typical pH meter consists of a special measuring probe (a glass electrode) connected to an electronic meter that measures and displays the pH reading
The meter circuit is no more than a voltmeter that displays measurements in pH units instead of volts. The input impedance of the meter must be very high because of the high resistance approximately 20 to 1000 M of the glass electrode probes typically used with pH meters. The circuit of a simple pH meter usually consists of operational amplifiers in an inverting configuration, with a total voltage gain of about -17. The inverting amplifier converts the small voltage produced by the probe (+0.059 volt/pH) into pH units, which are then offset by seven volts to give a reading on the pH scale. For example:
HPLC SECTION ATOMIC ABSORPTION SPECTROSCOPY:IntroductionAtomic absorption spectroscopy (AAS) determines the presence of metals in liquid samples. Metals include Fe, Cu, Al, Pb, Ca, Zn, Cd and many more. It also measures the concentrations of metals in the samples. Typical concentrations range in the low mg/L range. In their elemental form, metals will absorb ultraviolet light when they are excited by heat. Each metal has a characteristic wavelength that will be absorbed. The AAS instrument looks for a particular metal by focusing a beam of uv light at a specific wavelength through a flame and into a detector. The sample of interest is aspirated into the flame. If that metal is present in the sample, it will absorb some of the light, thus reducing its intensity. The instrument measures the change in intensity. A computer data system converts the change in intensity into an absorbance. As concentration goes up, absorbance goes up. The researcher can construct a calibration curve by running standards of various concentrations on the AAS and
observing the absorbances. In this lab, the computer data system will draw the curve for you! Then samples can be tested and measured against this curve.
PrincipleThe technique makes use of absorption spectrometry to assess the concentration of an analyte in a sample. It relies therefore heavily on Beer-Lambert law. In short, the electrons of the atoms in the atomizer can be promoted to higher orbitals for a short amount of time by absorbing a set quantity of energy (i.e. light of a given wavelength). This amount of energy (or wavelength) is specific to a particular electron transition in a particular element, and in general, each wavelength corresponds to only one element. This gives the technique its elemental selectivity.
As the quantity of energy (the power) put into the flame is known, and the quantity remaining at the other side (at the detector) can be measured, it is possible, from BeerLambert law, to calculate how many of these transitions took place, and thus get a signal that is proportional to the concentration of the element being measured.
Instrument DesignIn atomic absorption, there are two methods of adding thermal energy to a sample. A graphite furnace AAS uses a graphite tube with a strong electric current to heat the sample. In flame AAS, we aspirate a sample into a flame using a nebulizer. The flame is lined up in a beam of light of the appropriate wavelength. The flame (thermal energy) causes the atom to undergo a transition from the ground state to the first excited state. When the atoms make their transition, they absorb some of the light from the beam. The more concentrated the solution, the more light energy is absorbed!
The light beam is generated by a lamp that is specific for a target metal. The lamp must be perfectly aligned so the beam crosses the hottest part of the flame and travels into the detector. The detector the measures the intensity of the beam of light. When some of the light is absorbed by a metal, the beam's intensity is reduced. The detector records that reduction as an absorption. That absorption is shown on a read out by the data system. The figure above shows the schematic diagram of a flame AAS. As the diagram indicates, there are four primary parts to the system--the light source, the flame apparatus, the detector, and the data system. We can find the concentrations of metals in a sample running a series of calibration standards through the instrument. The instrument will record the absorption generated by a given concentration. By plotting the absorption versus the concentrations of the standards, a calibration curve can be plotted. We can then look at the absorption for a sample solution and use the calibration curves to determine the concentration in that
Light source The light source is usually a hollow-cathode lamp of the element that is being measured. Lasers are also used in research instruments. Since lasers are intense enough to excite atoms to higher energy levels, they allow AA and atomic fluorescence measurements in a single instrument. The disadvantage of these narrow-band light sources is that only one element is measurable at a time. Hollow cathode lamps Hollow cathode lamps are the most common radiation source in atomic absorption spectroscopy. Inside the lamp, filled with argon or neon gas, is a cylindrical metal cathode containing the metal for excitation, and an anode. When a high voltage is applied across the anode and cathode, gas particles are ionized. As voltage is increased, gaseous ions acquire enough energy to eject metal atoms from the cathode. Some of these atoms are in an excited states and emit light with the frequency characteristic to the metal. Many modern hollow cathode lamps are selective for several metals. Atomizer AA spectroscopy requires that the analyte atoms be in the gas phase. Ions or atoms in a sample must undergo desolvation and vaporization in a high-temperature source such as a flame or graphite furnace. Flame AA can only analyze solutions, while graphite furnace AA can accept solutions, slurries, or solid samples. Flame AA uses a slot type burner to increase the path length, and therefore to increase the total absorbance. Sample solutions are usually aspirated with the gas flow into a nebulizing/mixing chamber to form small droplets before entering the flame. The graphite furnace has several advantages over a flame. It is a much more efficient atomizer than a flame and it can directly accept very small absolute quantities of sample. It also provides a reducing environment for easily oxidized elements. Samples are placed directly in the graphite furnace and the furnace is electrically heated in several steps to dry the sample, ash organic matter, and vaporize the analyte atoms. Light separation and detection AA spectrometers use monochromators and detectors for uv and visible light. The main purpose of the monochromator is to isolate the absorption line from background light due to interferences. Simple dedicated AA instruments often replace the monochromator with a bandpass interference filter. Photomultiplier tubes are the most common detectors for AA spectroscopy.
GAS CHROMATOGRAPHY:Also known as Vapor Phase Chromatography A type of chromatography in which the mobile phase is an inert gas. Volatile components of sample are separated in the column and measured by a detector. OR Technique for separating chemical substances in which the sample is carried by a moving gas stream through a tube packed with a finely divided solid that may be coated with a film of a liquid is termed as Gas Chromatography.
Working:Gas Chromatography (GC) is used to separate volatile components of a mixture. A small amount of the sample to be analyzed is drawn up into a syringe. The syringe needle is placed into a hot injector port of the gas chromatograph, and the sample is injected. The injector is set to a temperature higher than the components boiling points. So, components of the mixture evaporate into the gas phase inside the injector. A carrier gas, such as helium, flows through the injector and pushes the gaseous components of the sample onto the GC column. It is within the column that separation of the components takes place. Molecules partition between the carrier gas (the mobile phase) and the high boiling liquid (the stationary phase) within the GC column. After components of the mixture move through the GC column, they reach a detector. Ideally, components of the mixture will reach the detector at varying times due to differences in the partitioning between mobile and stationary phases. The detector sends a signal to the chart recorder which results in a peak on the chart paper. The area of the peak is proportional to the number of molecules generating the signal. The main reason why different compounds can be separated this way is the interaction of the compound with the stationary phase. The stronger the interaction is the longer the compound remains attached to the stationary phase, and the more time it takes to go through the column (=longer retention time).
TYPES OF GAS CHROMATOGRAPHY:Gas chromatography can be divided into two types on the bases of Stationary phase. Gas Chromatography
Gas Liquid Chromatography (GLC)
Gas Solid Chromatography (GSC)
Gas - Liquid Chromatography :Gas-liquid chromatography (GLC) is a common type of chromatography in which the mobile phase is a gas (usually helium or nitrogen) and the stationary phase is a microscopic layer of liquid or polymer on an inert solid support inside a column. It is used in analytic chemistry for separating and analyzing compounds that can be vaporized without decomposition.
Gas Solid Chromatography :Gas-solid chromatography is a chromatography separation technique in which the mobile phase is a gas (usually helium or nitrogen) and the stationary phase is a suitable adsorbent such as silica gel, alumina or carbon. The technique is mostly used for the separation of the permanent gases or the low molecular weight hydrocarbons. Solute distribution occurs between the gaseous mobile phase (often called the carrier gas) and the surface of the adsorbent.
Carrier gasThe carrier gas must be chemically inert. Commonly used gases include nitrogen, helium, argon, and carbon dioxide. The choice of carrier gas is often dependant upon the type of detector which is used. The carrier gas system also contains a molecular sieve to remove water and other impurities.
Sample injection portFor optimum column efficiency, the sample should not be too large, and should be introduced into the column in the form of vapour - slow injection of large samples causes band broadening and loss of resolution. The most common injection method is where a micro syringe is used to inject sample through a rubber septum into a flash vaporizer port at the head of the column. The temperature of the sample port is usually about 50C higher than the boiling point of the least volatile component of the sample. For packed columns, sample size ranges from tenths of a micro liter up to 20 micro liters. Capillary columns, on the other hand, need much less sample, typically around 10-3 L.
ColumnsThere are two general types of column, packed and capillary (also known as open tubular). Packed columns contain a finely divided, inert, solid support material (commonly based on diatomaceous earth) coated with liquid stationary phase. Most packed columns are 1.5 - 10m in length and have an internal diameter of 2 - 4mm. Capillary columns have an internal diameter of a few tenths of a millimeter. They can be one of two types; wall-coated open tubular (WCOT) or support-coated open tubular (SCOT). Wall-coated columns consist of a capillary tube whose walls are coated with liquid stationary phase. In support-coated columns, the inner wall of the capillary is lined with a thin layer of support material such as diatomaceous earth, onto which the stationary phase has been adsorbed. SCOT columns are generally less efficient than WCOT columns. Both types of capillary column are more efficient than packed columns. Column temperature The column(s) in a GC are contained in an oven, the temperature of which is precisely controlled electronically. (When discussing the "temperature of the column," an analyst is technically referring to the temperature of the column oven.) The rate at which a sample passes through the column is directly proportional to the temperature of the column. The higher the column temperature, the faster the sample
moves through the column. However, the faster a sample moves through the column, the less it interacts with the stationary phase, and the less the analytes are separated. Material of Column: Stainless Steel Aluminum (Soft material so it is turned easily) Copper (Soft material so it is turned easily, it is mostly used for circular shape column) Glass Nickel
Adsorbent for Packing of Column: Silica Gel Glass Beads Activated Carbon Molecular Sieve
Properties of Solid Support: It should be small and uniform in size. Inert at high temperature. Good mechanical strength. Liquid phase coated uniformly. Liquid phase coated strongly.
Properties of Liquid phase. High thermal stability. Low thermal reactivity. Low vapour pressure at high temperature.
DetectorsThere are many detectors which can be used in gas chromatography. Commonly used detectors are; Mass Spectrometer (GC/MS) Many GC instruments are coupled with a mass spectrometer, which is a very good combination. The GC separates the compounds from each other, while the
mass spectrometer helps to identify them based on their fragmentation pattern. Flame Ionization Detector (FID) The detector is very sensitive towards organic molecules (10-12 g/s, linear range: 106 107), but relative insensitive to a few small molecules e.g. N2, NOx, H2S, CO, CO2, H2O. If proper amounts of hydrogen/air are mixed, the combustion does not afford any ions. If other components are introduced that contain carbon atoms cations are produced in the effluent stream. The more carbon atoms are in the molecule, the more fragments are formed and the more sensitive the detector is for this compound (-- > response factor). However, due to the fact that the sample is burnt (pyrolysis), this technique is not suitable for preparative GC. In addition, several gases are usually required to operate a FID: hydrogen, oxygen (compressed air), and carrier gas. Thermal Conductivity Detector (TCD) This detector is less sensitive than the FID (10-5-10-6g/s, linear range: 103-104), but is well suited for preparative applications, because the sample is not destroyed. It is based on the comparison of two gas streams, one containing only the carrier gas, the other one the carrier gas and the compound. Naturally, a carrier gas with a high thermal conductivity e.g. helium or hydrogen is used in order to maximize the temperature difference (and therefore the difference in resistance) between two thin tungsten wires. The large surface-to-mass ratio permits a fast equilibration to a steady state. The temperature difference between the reference cell and the sample cell filaments is monitored by a Wheatstone bridge circuit. Electron Capture Detector (ECD) The detector consists of a cavity that contains two electrodes and a radiation source that emits b-radiation (e.g. 63Ni, 3H). The collision between electrons and the carrier gas (methane plus an inert gas) produces a plasma containing electrons and positive ions. If a compound is present that contains electronegative atoms, those electrons are captured and negative ions are formed, and the rate of electron collection decreases. The detector is extremely selective for compounds with atoms of high electron affinity (10-14 g/s), but has a relatively small linear range (~102-103). This detector is frequently used in the analysis of chlorinated compounds e.g. pesticides, polychlorinated biphenyls, which show are very high sensitivity.
Data reduction and analysis:
Generally chromatographic data is presented as a graph of detector response (y-axis) against retention time (x-axis), which is called a chromatogram. This provides a spectrum of peaks for a sample representing the analytes present in a sample eluting from the column at different times. Retention time can be used to identify analytes if the method conditions are constant. Quantitative analysis: The area under a peak is proportional to the amount of analyte present in the chromatogram. By calculating the area of the peak using the mathematical function of integration, the concentration of an analyte in the original sample can be determined
FACTORS INFLUENCE SEPERATION:Polarity of the stationary phase Polar compounds interact strongly with a polar stationary phase, hence have a longer retention time than non-polar columns. Temperature The higher the temperature, the more of the compound is in the gas phase. It does interact less with the stationary phase, hence the retention time is shorter, but the quality of separation deteriorates. Carrier gas flow If the carrier gas flow is high, the molecules do not have a chance to interact with the stationary phase. The result is the same as above. Column length The longer the column is the better the separation usually is. The trade-off is that the retention time increases proportionally to the column length. There is also a significant broadening of peaks observed, because of increased back diffusion inside the column. Amount of material injected If too much of the sample is injected, the peaks show a significant tailing, which causes a poorer separation. Most detectors are relatively sensitive and do not need a lot of material (see below). Conclusion
High temperatures and high flow rates decrease the retention time, but also deteriorate the quality of the separation. USES OF GAS CHROMATOGRAPHY: Testing the purity of a particular substance. Separating the different components of a mixture (the relative amounts of such components can also be determined). In some situations, GC may help in identifying a compound. In preparative chromatography, GC can be used to prepare pure compounds from a mixture.
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY - HPLCHPLC is a popular method of analysis because it is easy to learn and use and is not limited by the volatility or stability of the sample compound. Modern HPLC has many applications including separation, identification, purification, and quantification of various compounds. High performance liquid chromatography is basically a highly improved form of column chromatography. Instead of a solvent being allowed to drip through a column under gravity, it is forced through under high pressures of up to 400 atmospheres. That makes it much faster. It also allows us to use a very much smaller particle size for the column packing material which gives a much greater surface area for interactions between the stationary phase and the molecules flowing past it. This allows a much better separation of the components of the mixture. The other major improvement over column chromatography concerns the detection methods which can be used. These methods are highly automated and extremely sensitive.
The column and the solvent
Confusingly, there are two variants in use in HPLC depending on the relative polarity of the solvent and the stationary phase. Normal phase HPLC This is essentially just the same as you will already have read about in thin layer chromatography or column chromatography. Although it is described as "normal", it isn't the most commonly used form of HPLC. The column is filled with tiny silica particles, and the solvent is non-polar - hexane, for example. A typical column has an internal diameter of 4.6 mm (and may be less than that), and a length of 150 to 250 mm. Polar compounds in the mixture being passed through the column will stick longer to the polar silica than non-polar compounds will. The non-polar ones will therefore pass more quickly through the column. Reversed phase HPLC In this case, the column size is the same, but the silica is modified to make it non-polar by attaching long hydrocarbon chains to its surface - typically with either 8 or 18 carbon atoms in them. A polar solvent is used - for example, a mixture of water and an alcohol such as methanol. In this case, there will be a strong attraction between the polar solvent and polar molecules in the mixture being passed through the column. There won't be as much attraction between the hydrocarbon chains attached to the silica (the stationary phase) and the polar molecules in the solution. Polar molecules in the mixture will therefore spend most of their time moving with the solvent. Non-polar compounds in the mixture will tend to form attractions with the hydrocarbon groups because of van der Waals dispersion forces. They will also be less soluble in the solvent because of the need to break hydrogen bonds as they squeeze in between the water or methanol molecules, for example. They therefore spend less time in solution in the solvent and this will slow them down on their way through the column. That means that now it is the polar molecules that will travel through the column more quickly. Reversed phase HPLC is the most commonly used form of HPLC.
Injection of the sampleInjection of the sample is entirely automated, and you wouldn't be expected to know how this is done at this introductory level. Because of the pressures involved, it is not the same as in gas chromatography (if you have already studied that). Retention time The time taken for a particular compound to travel through the column to the detector is known as its retention time. This time is measured from the time at which the sample is injected to the point at which the display shows a maximum peak height for that compound. Different compounds have different retention times. For a particular compound, the retention time will vary depending on:
the pressure used (because that affects the flow rate of the solvent) the nature of the stationary phase (not only what material it is made of, but also particle size) the exact composition of the solvent the temperature of the column
That means that conditions have to be carefully controlled if you are using retention times as a way of identifying compounds.
There are several ways of detecting when a substance has passed through the column. A common method which is easy to explain uses ultra-violet absorption. Many organic compounds absorb UV light of various wavelengths. If you have a beam of UV light shining through the stream of liquid coming out of the column, and a UV detector on the opposite side of the stream, you can get a direct reading of how much of the light is absorbed. The amount of light absorbed will depend on the amount of a particular compound that is passing through the beam at the time.
You might wonder why the solvents used don't absorb UV light. They do! But different compounds absorb most strongly in different parts of the UV spectrum. Interpreting the output from the detector The output will be recorded as a series of peaks - each one representing a compound in the mixture passing through the detector and absorbing UV light. As long as you were careful to control the conditions on the column, you could use the retention times to help to identify the compounds present - provided, of course, that you (or somebody else) had already measured them for pure samples of the various compounds under those identical conditions. But you can also use the peaks as a way of measuring the quantities of the compounds present. Let's suppose that you are interested in a particular compound, X. If you injected a solution containing a known amount of pure X into the machine, not only could you record its retention time, but you could also relate the amount of X to the peak that was formed.
The area under the peak is proportional to the amount of X which has passed the detector, and this area can be calculated automatically by the computer linked to the display. The area it would measure is shown in green in the (very simplified) diagram.
If the solution of X was less concentrated, the area under the peak would be less although the retention time will still be the same. For example:
This means that it is possible to calibrate the machine so that it can be used to find how much of a substance is present - even in very small quantities. Be careful, though! If you had two different substances in the mixture (X and Y) could you say anything about their relative amounts? Not if you were using UV absorption as your detection method.
In the diagram, the area under the peak for Y is less than that for X. That may be because there is less Y than X, but it could equally well be because Y absorbs UV light at the wavelength you are using less than X does. There might be large quantities of Y present, but if it only absorbed weakly, it would only give a small peak.
SEMI-SOLID MANUFACTORING: PRODUCTS NAME: Artifen Gel Brufen cream Froben Gel Somo Gel Rashnil Cream Tronolane Cream
(a) ARTIFEN GEL:1g. Artifen gel contains an amount of Diclofenac Diethylammonium equivalent to active substance diclofenac 10mg. (1%).(b)
. Per 100g the active ingredient ibuprofen 10gm is used.
(c) FROBEN GEL:Per 100gm, the active ingredient used is Fluriprofen 5gm.
(d) SOMO GEL:Lignocaine (Base) Menthol Eucalyptol Cetylpyridinium chloride Ethanol (e) RASHNIL CREAM: Benzalkonium Chloride 0.1% w/w Zinc Oxide 8.5% w/w 0.60% w/w 0.06% w/w 0.10% v/w 0.02% w/w 33% v/w
(f) TRONOLANE CREAM:Each 20gm contains pramoxine hydrochloride.
INTRODUCTION:Transdermal drug delivery system delivers drug systematically through the skin but without the use of any instrument to inject them. The system is applied to the skin and is absorbed by a process of molecular diffusion. The diffusion process begins as soon the system is applied to the skin. In the beginning the process is quite fast till the binding sites of the skin are saturated then the release of drug settles at a constant rate. Semi-solid includes ointments, creams, gels, clear gels and pastes. They may serve as vehicles for topically applied drugs, as emollients, or as protective or occlusive dressings on the skin.
TYPES OF SEMI-SOLID:(a) Ointments.These are soft, semi-solid preparations intended for application to the skin and may consist of hard and soft paraffins, vegetable oils, synthetic esters of fatty acids, animal fats and many other materials. These substances may be used singly or in multiple combinations, with the incorporation of medicaments and sometimes surface active agents. Properties which affect choice of an ointment base are: 1. 2. 3. 4. 5. Stability Penetrability Solvent property Irritant effects Ease of application and removal
Methods of preparation of ointments: Trituration: In this finely subdivided insoluble medicaments are evenly distributed by grinding with a small amount of the base followed by dilution with gradually increasing amounts of the base. Fusion: In this method the ingredients are melted together in descending order of their melting points and stirred to ensure homogeneity.
(b) Creams.These are viscous semi-solid emulsions for external use and may be oil in water (o/w) i.e. non-greasy, or water in oil (w/o) i.e. greasy. Emulsifying agents for o/w creams include monovalent inorganic and organic soaps and anionic, cationic and nonionic emulsifying waxes. Those for w/o creams include wool fat, wool alcohols, combinations of beeswax and borax, calcium soaps and surfactants of low H.L.B. Creams are able to support the growth of micro-organisms, and it is therefore necessary to use preservatives in most systems. Accidental contamination will almost
certainly occur during bench scale manufacture, but good technique can keep this to a minimum. All apparatus and final containers should be thoroughly cleansed before use and purified water should be used in the preparation of products. Uses of creams
The provision of a barrier to protect the skin. This may be a physical barrier or a chemical barrier as with sunscreens To aid in the retention of moisture (especially water-in-oil creams) Cleansing Emollient effects As a vehicle for drug substances such as local anaesthetics, anti-inflammatories (NSAIDs or corticosteroids), hormones, antibiotics, antifungals or counterirritants.
(c)Gels.Gels encompass semi-solids with a wide range of characteristics. They can be considered as being composed of two interpenetrating phases. In simplistic terms they fall into two major classes; suspensions of small inorganic particles or large organic molecules interpenetrated with liquid. (d) Clear gels. Clear gels are microemulsions in which the diameter of the dispersed phase globules is in the range of 10 to 60 nm. These emulsions are thermodynamically stable. Microemulsions are transparent as the globule diameter of the disperse phase is less than the wavelength of light. Microemulsions can be distinguished from other types of gels by the vibrations or ringing that occurs when the emulsion is subjected to impact.
(e) Pastes.These are semi-solid preparations containing large proportions of solids finely dispersed in the basis. They are usually intended to be applied to small localised areas of the skin. Pastes should be stored at temperature not exceeding 250C unless otherwise stated. Pastes are used principally as antiseptic, protective or soothing dressings. Their consistency is much stiffer than that of ointments and so they are usually spread on gauze or lint before being applied.
PERPARATION OF SEMI SOLID:These are following step for the preparation of semi-solids.
Line clearance Dispensing/Warehouse section Mixing section Filling section Packaging section PCI i.e Production Control Inspector.
LINE CLEARENCE:Line clearance is check by worker, supervisor as well as PCI i.e Production Control Inspector. The line clearance include following steps: Check pressure, temperature as per SOP requirement. Check gas protection where required. Check the equipment/area is cleaned. Check no identity sign from previous batch. Check required commodities of the batch area available as per finishing shop order. Check exhaust are operational in powder filling. Check product name and strength on almonium foil.
DISPENSING/WARE HOUSE SECTION:In this section following step is done: The raw material is collected as per STM or as define in direction. The weighing of raw material is done under control environment with proper labeling.
MIXING SECTION:In mixing section the mixing of different phases occur that is define in direction. For example in cream there are two phases one is aqueous while other is alcoholic. These two phases are prepared in different chamber with different condition that are define in direction. Then these phases are mixed together. In mixing section we have following equipments that are defined below. Batch reactor. Silverson mixer. Storage tank.
Within the chemical and pharmaceutical industries, external cooling jackets are generally preferred as they make the vessel easier to clean. The performance of these jackets can be defined by 3 parameters:
Response time to modify the jacket temperature Uniformity of jacket temperature Stability of jacket temperature
A chemical reactor in which the reactants and catalyst are introduced in the desired quantities and the vessel is then closed to the delivery of additional material. The Batch reactor is the generic term for a type of vessel widely used in the process industries. Vessels of this type are used for a variety of process operations such as solids dissolution, product mixing, chemical reactions, batch distillation, crystallization, liquid/liquid extraction and polymerization.
A typical batch reactor consists of a tank with an agitator and integral heating/cooling system. These vessels may vary in size from less than 1 litre to more than 15,000 litres. They are usually fabricated in, stainless steel. Liquids and solids are usually charged via connections in the top cover of the reactor. Vapors and gases also discharge through connections in the top. Liquids are usually discharged out of the bottom.
The advantages of the batch reactor lie with its versatility. A single vessel can carry out a sequence of different operations without the need to break containment. This is particularly useful when processing, toxic or highly potent compounds.
Agitation The usual agitator arrangement is a centrally mounted driveshaft with an overhead drive unit. Impeller blades are mounted on the shaft. A wide variety of blade designs are used and typically the blades cover about two thirds of the diameter of the reactor. Where viscous products are handled, anchor shaped paddles are often used which have a close clearance between the blade and the vessel walls. With propeller scrapper is also introduce in reactor because of the fact that cream, gel e.t.c are very viscous in nature and hence need scrapper for efficient mixing. Most batch reactors also use baffles. These are stationary blades which break up flow caused by the rotating agitator. These may be fixed to the vessel cover or mounted on the side walls. Despite significant improvements in agitator blade and baffle design, mixing in large batch reactors is ultimately constrained by the amount of energy that can be applied. On large vessels, mixing energies of more than 5 Watts per litre can put an unacceptable burden on the cooling system. High agitator loads can also create shaft stability problems. Where mixing is a critical parameter, the batch reactor is not the ideal solution. Much higher mixing rates can be achieved by using smaller flowing systems with high speed agitators, scrapper, ultrasonic mixing or static mixers. Heat cooling systems Products within batch reactors usually liberate or absorb heat during processing. Even the action of stirring stored liquids generates heat. In order to hold the reactor contents at the desired temperature, heat has to be added or removed by a cooling jacket or cooling pipe. Heating/cooling coils or external jackets are used for heating and cooling batch reactors. Heat transfer fluid passes through the jacket or coils to add or remove heat. It can be argued that heat transfer coefficient is also an important parameter. It has to be recognized however that large batch reactors with external cooling jackets have severe heat transfer constraints by virtue of design. It is difficult to achieve better than 100 Watts/litre even with ideal heat transfer conditions. By contrast, continuous reactors
can deliver cooling capacities in excess of 10,000 W/litre. For processes with very high heat loads, there are better solutions than batch reactors. Fast temperature control response and uniform jacket heating and cooling is particularly important for crystallization processes or operations where the product or process is very temperature sensitive. There are several types of batch reactor cooling jackets:
Single external jacket
The single jacket design consists of an outer jacket which surrounds the vessel. Heat transfer fluid flows around the jacket and is injected at high velocity via nozzles. The temperature in the jacket is regulated to control heating or cooling. The single jacket is probably the oldest design of external cooling jacket. Despite being a tried and tested solution, it has some limitations. On large vessels, it can take many minutes to adjust the temperature of the fluid in the cooling jacket. This results in sluggish temperature control. The distribution of heat transfer fluid is also far from ideal and the heating or cooling tends to vary between the side walls and bottom dish. Another issue to consider is the inlet temperature of the heat transfer fluid which can oscillate (in response to the temperature control valve) over a wide temperature range to cause hot or cold spots at the jacket inlet points.
CAPACITY:There are three type of capacities used in Abbott. 400kg 800kg 1000kg
Storage vessels/tanks are simple vessels used for storing liquids, solutions or pharmaceutical raw material and other chemicals. These general purpose vessels are made of stainless steel, fibre glass, titanium, galvanized steel etc. and are used by a number of industries to store various substances and solutions. Storage tanks/vessels can either be horizontal or vertical in their orientation. Horizontal storage vessel is generally mounted on stands or saddles and have an access port either at the bottom or at the top. Vertical storage tanks are erected vertically and have access ports at bottom. These specialized tanks can either be placed above or underground, depending on the construction of the storage facility. The thickness of wall of these tanks/vessels also determine their application or use; while single wall storage tanks can be used for general application, double walled tanks/vessel are used for high pressure considerations.
In pharmaceutical industry, Silverson has In-Line mixers, top and bottom entry immersion/batch mixers and powder/liquid mixing systems. Silverson High Shear Bottom Entry Mixers are increasingly being specified by the pharmaceutical sector for applications where focused high shear in-tank mixing is required. Using their expertise in the design and manufacture of Ultra Hygienic In-Line and top entry batch mixers, Silverson have advanced their range of Bottom Entry mixers incorporating specific features, for example minimized number of product contact parts, "crevice-free" design, electro-polished finish, and special hygienic shaft seals. Complete documentation packages and data manuals including IQ/OQ documentation to comply with FDA and GMP requirements can also be supplied. These mixers can be used in conjunction with slow speed stirrer/scraper units, the action of the two being complementary to one another, the Silverson rotor/stator work head providing high shear which stirrer/scraper units cannot impart. The stirrer/scraper unit complements this action by distributing the homogenized output of the bottom entry mixer uniformly throughout the vessel. This combination is ideal for high viscosity products, those that increase in viscosity on cooling - for example, pharmaceutical creams and ointments - and where heat sensitive materials such as active ingredients may only be added at low temperatures.
FILLING SECTION:The filling is done by two machine named kali having capacity
Kali having 1000 kg Unipack having 400kg
There is no contamination occur in the tube by supplying air as well as simultaneously supplying vacuum in the same tube. There is also a sensor present that locate the direction where expire date, batch number is printed. The cream or gel is filled and simultaneously sealed by the machine. The tube filling, crimping and coding machine is sturdy compact in design and simple in operation. It consists of an aluminium-rotating disc with interchangeable tube holding sockets for different tube sizes. The filling station is made of SS Block, fitted with pneumatic device to control tailing. No tube no fill process switches. (Electronic counter provided if required, not included in basic machine) S.S plain hopper of 25 kg capacity.
KALI FILLING MACHINEFEATURE: All contact parts easily detachable for cleaning and sterilization. Thermostatically controlled jacketed heater with stirrer. All operations are automatic except loading of the containers on the turntable. No need of costlier spares as in the case of ultrasonic sealing machines with heaters. Fill accuracy: + 98.8 %. Accurate tail cutting arrangement. PLC controlled alarm for any abnormal performance during filling operation. Output up to 70+ Tubes/minute. Can fill from 3 Grams to 500 Grams with change parts. (Change parts available on request) GMP model contact parts SS 304 / SS 316 (As per customer requirement). Power consumption 0.75 HP, 230 Volts / 415 Volts. Sensors embedded in hopper to stop overflowing and also pause machine in
case of low level of cream to avoid tube wastage.
UNIPACK FILLING MACHINE: FEATURES:
Fully pneumatic and 95% maintenance free. Tube holders are of spring loaded type to take care of any tube diameter variation. Output up to 50 - 55 Tubes/minute. Can fill from 3 Grams to 500 Grams with change parts. GMP model contact parts SS 304 / SS 316 (As per customer requirement). Power consumption 0.75 HP, 230 Volts / 415 Volts.
It is fully automatic. Production counters with memory to indicate the number of filled tubes. Tube orientation device incorporating photo sensors and stepper motor and controller. (optional) Automatic cream level sensing device. (optional
PACKAGING AREA:In packaging area the tubes are packed in cartons and then LOCPS. Then it is marketed.
PRODUCTION COTROL INSPECTOR:The PCI check the following test during production
Check FO i.e expiry slip and batch number on the tube. To check line clearance. Take three empty tubes marked them and filled them with cream by machine and then perform weight uniformity and leak test by applying 500mm of Hg pressure for 3-4 hr.
LIQUID MANUFACTORING: PRODUCT NAME: 1.
Iberet drop. Vidaylin drop. Rondec-D drop. Cecon solution. Silver suspension. Vidaylin syrup. Surbex syrup. Rondec-C syrup. Iberet solution. Vidaylin-L syrup Epival syrup. IBERETDROPS
Per ml : Ferrous sulphate 125mg (represents 25 mg of elemental iron The liquid department is divided into five sections:
VI-DAYLIN DROPS Each 0.6 ml of Vi-Daylin Drops contains:
Vitamin A Vitamin D Vitamin B1 Vitamin B2 Vitamin B6 Vitamin C Nicotinamide in citrus flavour with a calibrated dropper
1.5 mg or 5000 IU 10 mcg or 400 IU 1.5 mg 1.2 mg 0.5 mg 50 mg 10 mg
VIDAYLIN-L SYRUP Each 5 ml teaspoonful of ViDaylin-L Syrup contains:
Vitamin A Vitamin D Vitamin B1 Vitamin B2 Vitamin B6 Vitamin B12 Vitamin C Nicotinamide Choline Inositol Lysine Monohydrochloride
0.9 mg or 3000 IU 10 mcg or 400 IU 1.5 mg 1.2 mg 1.0 mg 3 mcg 50 mg 10 mg 5 mg 5 mg 300 mg
VI-DAYLIN SYRUP Each 5 ml teaspoonful of Vi-Daylin Syrup contains:
Vitamin A Vitamin D Vitamin B1 Vitamin B2 Vitamin B6 Vitamin B12 Vitamin C
0.9 mg or 3000 IU 10 mcg or 400 IU 1.5 mg 1.2 mg 1.0 mg 3 mcg 50 mg
Nicotinamide in delicious lemon candy flavor
CECON DROP: Each ml. contains 100 mg of vitamin C in a vehicle of propylene glycol
RONDEC SYRUP Each teaspoonful (5ml.) provides:
Dextromethorphan hydrobromide......10 mg Chlorpheniramine maleate ...........2 mg Ephedrine hydrochloride ............5 mg Phenylephrine hydrochloride ........5 mg Ammonium chloride ..................40 mg7.
RONDEC C SYRUP Each teaspoonful (5ml.) provides:
Dextromethorphan HBr ...........7.5 mg Carbinoxamine maleate ..........1.25 mg Pseudoephedrine HCl ............30 mg Guaifenesin ....................50 mg Ipecac fluid extract ...............0.005 ml8.
RONDEC D ORAL DROPS Each dropperful (1ml.) contains:
Carbinoxamine maleate 1.0 mg Pseudoephedrine HCl 30 mg
SILLIVER Silymarin 200mg
Each 5 mL of Surbex Syrup contains the following ingredients: Vitamin C (as Ascorbic acid) 100 mg Nicotinamide Vitamin B1 Vitamin B2 Pantothenol Vitamin B6 Vitamin B12 50 mg 10 mg 6 mg 10 mg 10 mg 10 mcg
BERET-500 Liquid: Per 5ml: Ferrous sulphate 131 mg (represents 26.25mg of elemental iron), Vit C 125mg, B1 1.5mg, B2 1.5mg, B6 1.25mg, B12 6.25mcg, Nicotinamide 7.5mg and Dexpanthenol 2.5mg
PREPARATION OF LIQUID:The area is further divided into following:1. Syrup manufacturing.
2. Pedialyte manufacturing area. 3. GHC (general health care) production area.
SYRUP MANUFACTURING AREA:
INTRODUCTION OF SYRUP:Syrup is a concentrated or nearly saturated solution of sucrose in water. Simple syrup contains only sucrose and purified water (e.g. syrup USP). Syrup containing pleasantly flavored substances is known as flavoring syrup (e.g. Cherry syrup, Acacia syrup, etc).medicinal syrups are those to which therapeutic compounds have been added (e.g. cough syrup). Syrup USP contains 850 gm sucrose and 450 gm of water in each liters of syrup. Although very concentrated the syrup is not saturated. Since 1 gm sucrose dissolves in 0.5 ml of water, only 425 ml of water would be required to dissolve 850 gm sucrose. This slight excess of water enhances the syrups stability over a range of temperatures, permitting cold storage without crystallization. This high solubility of sucrose indicates a high degree of hydration or hydrogen bonding between sucrose and water. This association limits the further association between water and additional solutes. Hence, syrup has a lower power than water and salting out may be a problem.
PRESERVATION OF SYRUPS:Syrup, USP is protected from bacterial contamination by virtue of its high solute concentration. More dilute syrups are good media for microbial growth and require the addition of some preservatives. Industrially formulated syrups often contain ingredients to improve solubility, stability, taste or appearance which also contribute to product preservation. It is necessary from an economical point of view to consider the additives preservative effect of such ingredients as alcohol, glycerin, propylene glycol and other dissolve solids. Syrup USP having a specific gravity of 1.313 and a concentration of 85% w/v is a 65% w/w solution. This 65 % w/w is the minimum amount of sucrose, the
quantity of alcohol, or other preservatives, may be estimated by considering the USP syrup equivalent and the free water equivalent. One may assume that free water is preserved by 18% alcohol
PREPARATION OF SYRUPFor manufacturing of syrup Abbott manufacturers have to follow. Manufacturing order. Manufacturing direction. In Manufacturing order there is a demand that of how much quantity a batch must have to prepare and all the quantities of raw materials are provided so according to this the production demands raw materials from the quarantine section, and at what date this has to be sent to the finishing area i.e. for filling and packing. In Manufacturing direction there provided the steps by using a product can be manufactured in this direction conditions of temperature and pressure ranges also provided.
Steps for the preparation of syrup are: Line clearance. Dispensing. Preparation of sugar base solution. Preparation of saturated water. Final preparation of syrup. Storage syrup. Washing of bottles. Filling of bottles PCI:
Line clearance is check by worker, supervisor as well as PCI i.e Production Control Inspector. The line clearance include following steps: Check pressure, temperature as per SOP requirement. Check gas protection where required. Check the equipment/area is cleaned. Check no identity sign from previous batch. Check required commodities of the batch area available as per finishing shop order. Check exhaust are operational in powder filling. Check product name and strength on almonium foil.
DISPENSING:It is the first step of process and carried out in warehouse, dispensing is the process of weighing of raw materials.
PREPARATION OF SUGAR BASE SOLUTION:Sugar is treated with steam and prepares the sugar solution. It is transferred in double jacketed vessel for cooling.
Liquid manufacturing vessels are specialised vessels used to manufacture high quality liquids and solutions required in pharmaceutical industry and other industries. These vessel are equipped with MS/SS steam jackets and insulation with SS cladding for uniform heating of the liquid. The vessel also have a direct top mounted stirrer available with or without top dish; different types of stirrers are available with the vessel including propeller, pedal, anchor etc. The capacity can range from 50 liters to 10000 liters and more depending on individual requirements.
PREPARATION OF C02/ N2 SATURATED WATER:a. In a separate covered S.S vessel, heat required amount of water purified (measured by dipstick) to boiling for 30 minutes. b. Turn off heat & cool the water purified to room temperature while continue purging the water with C02/ N2 gas for two hours.
FINAL PREPARATION OF SYRUP:Presoaked materials, sugar based solution are added in the double jacketed steam vessel which is provided with the agitators for mixing, then add active ingredients, preservatives, flavoring agents, coloring agents & essence all are added with different time periods & at different temperatures according to the manufacturing order. After addition of each ingredient mixing is carried out and checks clarity of solution. If solution is not clear than again mix the solution for 15-20 minutes. Volume of syrup is maintained by De-ionized water.
STORAGE:After manufacturing, syrups are stored in storage tanks & after passing from QC it is allowed for filling & packing area by the help of pumps. Capacity of storage tanks are 3,000 liters made-up of stainless steel.
BOTTLE WASHING:There is a separate section for washing of bottles in order to make bottles free from any dirt, impurity and microbial contamination.
Bottle washing machine:Bottle washing machine consists of 26 manifolds and eight needles in a bottle washing machine in which compressed air is passing and it passes to another room through the same machine there sterilized by the help of dry heat sterilization at 210C.
FILLING OF BOTTLES:In the manufacturing area, there is an automatic filling system for transferring syrup from holding vessel to filling area. The filling also have automatic valve system, this set the flow rate of the syrup according to their requirement. According to that floe rate, a machine fills the required amount of syrup and then stopped. After filling of syrup in bottles, it comes for packing.
FEATURE:Voltage: 220/110V 50/60HZ Power (w): 500 Air Pressure (mpa):0.5-0.7
Current: 3A Filling speed: 20-50 bottles/min
LABELLING AND PACKING OF BOTTLES: Labeling is done manually.
For packing, there are six belts, both automatic and manual. Five belts are manual. Only one is automatic named autocartnor packs 85,000 bottles/day.
A conveyor belt then carries the labeled bottles to another turntable. This provides the bottles to the cam cartoons, the cartooning machine, which is fully automatic. The cartons are provided from one side, picked up one at a time through the suction pump. The machine then itself opens the cartons. Places the filled bottles in it and then folds the flaps to the packed position.
PCI SECTION:Here in this area, checking is very strict, and done by PCIS (production control inspector). The volumes and weights are inspected they should be accurate. After capping bottles comes on the turntable workers are present on the belt for labeling, they check the Batch no, Manufacturing Date, Expiry, Retail price. Check line clearance. Leak test by applying 20 inches of Hg Hardness test Capping test. Check pH, viscosity, and microscope. Check weight variation. Check torque test which will not less than 5 torr.
PEDIALYTE MANUFACTURING AREA:
INTRODUCTION:Pedialyte is sterilized oral glucose electrolyte solutions intended for the management of dehydration secondary to diarrhea. Pedialyte is formulated to replace fluid and electrolyte losses in diarrheal stools. Glucose enhances the absorption of sodium and water in the small intestine, and helps to prevent tissue catabolism.
PREPARATION OF PEDIALYTE:In the manufacturing of pedialyte electrolyte oral solution number of steps are involved which are described as follows. Preparation of oral solution. HDPE bottles washing. Filling Sealing Leak test Sterilization
PREPARATION OF THE ORAL SOLUTION: Solution prepared in glass-lined or a 316 grade stainless steel tank, cleaned a/c to SOPS. Deionized water should use. Volume of water is checked by calibrated dipstick. Add & dissolve with mixing the following items Sodium citrate Sodium chloride Potassium citrate Dextrose powder hydrous Stir for ten minutes or until all the ingredients are dissolve. Maximum holding time of product is 12 hours. Adjust PH 5.6 (B/E 5.4-5.8) with 40% citric acid solution. Makeup the final volume of solution by deionized water.
H.D.P.E(High density polyethylene) BOTTLES WASHING :The empty bottles are washed on H.D.P.E bottles washing machine. This machine is consist of 26 manifolds each contains 3 nozzles & 8 washing stations. The mashing cycle include compressed air (C.A), fresh water (F.W), and hot deionized water (H.D.W).
WASHING STATION: C.A--- F.W--- F.W--- F.W--- C.A --- HDW --- HDW --- C.A
Filtration of solution is done by using 0.8 microns membrane filtration unit.
Filling of bottles up to 500 ml by pedialyte solution on machine.
SEALING:Sealing of filled bottles by the help of Aluminum foil at 315C, contact time is 4 seconds.
LEAK TEST:To check leakage applies pressure on sealed bottles up to 0.2 kg/sq.in.
STERILIZATION OF FILLED & SEALED BOTTLES: Super heated water autoclave equipped with circulated hot water spray is used for sterilization of pedialyte bottles. Place bottles in autoclave art 115C for 30-35 min.
Place atleast 4 thermocouples on different locations in autoclave One functioning thermocouple located in solution filled containers to indicates & record the time & temp employed. Air over pressure is employed in order to maintain autoclave pressure. Pressure should be gradually increased to a max of 28 psig. After complete sterilization cool down the bottles by gradually decreasing thr air over pressure until 4 psig is reach. Then after sterilization bottles are sent to the finishing area for labeling & packing.
How supplied:500ml sterile solution in Aluminum sealed plastic bottle. Available in apple, Strawberry, Bubble-gum and regular flavors.
GHC (general health care) PRODUCTION AREA:In GHC area following products are manufactured;
Mospel liquid 120 ml. Selsun 205% Selsun blue balance treatment 80 ml/100 ml. Selsun blue moisturizing treatment 80 ml/100 ml.
MOSPEL:Ingredient(s): 50 ml bottle contains: Diethyltoluamide- A mosquito repellent. Indications : Mospel is an effective mosquito repellent. Pack Size: 50ml bottle
SELSUN BLUE MOISTURIZING TREATMENTIngredient(s): Selenium Sulfide..1% concentrations. Selsun Blue is indicated for the treatment of dandruff and seborrheic dermatitis of the scalp. Dandruff control for dry scalp, damaged or chemically treated hairs.
SELSUN 2.5%Ingredient(s): Selenium Sulfide 2.5% w/v. Selsun is indicated for the treatment of dandruff, tinea versicolor, and seborrheic dermatitis of the scalp.
SELSUN BLUE BALANCED TREATMENTIngredient(s): Selenium Sulfide..1% concentrations Selsun Blue is indicated for the treatment of dandruff and seborrheic dermatitis of the scalp. Dandruff control for all types of hairs.
INJECTION MANUFACTORING PRODUCT NAME: Abocain spinal injection. Abozole injection Acyclovir injection Artifen injection. Bejentan injection. Bevidox injection. Dopamine HCl injection 200MG. Epival injection. Klaricid injection. Trividox injection. Lincomycin injections. Vancomycin injection Sterilize water.
Each ml of solution contains:
Bupivicaine Hcl : 7.5mg Dextrose anhydrous : 82.5mg (b) ACYCLOVIR
Each 10ml vial contains: Acyclovir Sodium equivalent to Acyclovir 500mg (c) DOPAMINE
HCL INJECTIONS 200MG
Each ml contains: 40mg/ML Dopamine Hydrochloride (d) TRIVIDOX
Each 3 ml of solution contains: Thiamine HC1 ( B1 ) 100 mg Pyridoxine HC1 ( B6) 30 mg 1000 Cyanocobalamin ( B12) mcg
VANCOMYCIN INJECTIONS 1.0GM Each vial contains: 1.0 gram Vancomycin Hydrochloride (lyophilized) equivalent to vancomycin 1.0 gram 500MG Each vial contains: Vancomycin Hydrochloride quivalent to vancomycin 500mg
Each 5 ml ampoule contains: Buflomedil Hydrochloride.50 mg (g)
Each ml contains: Metronidazole.................................5mg Sodium Chloride.................................7.9mg Dibasic sodium phosphate, anhydrous.........0.48mg Citric acid, anhydrous....................0.23mg. (h) ARTIFEN
Each 3ml ampoule contains: Diclofenac Sodium. 75mg. (i) BEJECTAL: Each ml contains Vitamin B1 C Vitamin B2 vitamin B6 Nicotinamide Dexpanthenol (j) BEVIDOX 10 mg 2 mg 5 mg 75 mg 5 mg
Bevidox is a parenteral solution of vitamins B1, B6, and B12 for the direct intramuscular injection or intravenous infusion after dilution with an appropriate intravenous solution. Each 3ml ampoule contains: Thiamine HC1 ( B1 ) 100 mg Pyridoxine HC1 ( B6) 100 mg Cyanocobalamin ( B12) 1000 mc. (k) KLARICID
Klaricid I.V., is a lyophilized powder containing clarithromycin lactobionate equivalent to 500 mg clarithromycin per vial (l) EPIVAL
Valproate Sodium 500mg/5ml. Each 5ml contains Valproate sodium equivalent to 500 mg valproic acid (100mg/ml)
INTRODUCTION:An injection (often referred to as a "shot" or a "jab") is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body. An injection follows a parenteral route of administration, that is, administered other than through the digestive tract. OR Injections are the sterile liquid preparations containing one or more medicaments dissolved or suspended in a suitable vehicle and are meant for introduction into the body tissues by means of an injection under or through one or more layers of the skin or mucous membarne.
TYPES OF INJECTION:
Types with respect to roots of administration of injection: Intravenous injection Intramuscular injection Subcutaneous injection
INTRAVENEOUS INJECTION:Intravenous injections are applied into the vein. USED: They are used when rapid action of drug is required.
INTRAMUSULAR INJECTION:An intramuscular (IM) injection is a shot. The needle goes into the muscle to deliver medicine.IM injections are deeper than subcutaneous injections (given under the skin). USED:
Some medicines are better absorbed when given in the muscle; if taken by mouth, they may not work. Some medications are put in the muscle and absorbed slowly over time. Other medications are put in the muscle because they are absorbed faster and, if taken by mouth, would not be effective. These medications may be given using an IM injection:
Certain antibiotics Certain contraceptive hormones Most vaccines Epinephrine injections for severe allergic reactions
A needle passes through skin and fat layers into the muscle fibers to deliver medicine It is used where rapid absorption is required through many blood vessel found in muscles.
SUBCUTANEOUS INJECTION:A subcutaneous (Sub-Q) injection is a shot that delivers medicine into the fat layers between the skin and the muscle. The drug moves from the small blood vessels into the bloodstream.
Used: Some medicines need to be injected because they are not effective if taken by mouth. Subcutaneous injections are a easy way to deliver this type of medicine. Examples of medicines given sub-Q include:
Insulin for people with diabetes Low molecular weight heparin (eg, enoxaparin) to prevent blood clots
Body tissue layers
TYPES OF INJECTION BOTTLES:There are two types of injection bottels Ampoul Vial AMPOUL: An ampoule (also ampule or ampulla) is a small sealed bottle made up of glass or plastic that contain a sterile medicinal solution or a powder to be made into a solution for subcutaneous, intramuscular, or intravenous injection.
VIAL: A vial (also phial) is a relatively small glass vessel or bottle, especially used to store medication as liquids, powders or in other forms like capsules. They can also be sample vessels e.g. for use in autosampler devices in analytical chromatography.
RUBBER CLOSURES FOR VIALS: Each vial is sealed with a rubber closure in place by an aluminium cap.rubber closures are composed of multiple ingredients that are plasticized and mixed together at an elvated temperature.The physical properties to be considerd in the selection of a
perticular formulation include elasticity, hardness, tendency to fragment and permeability to vapour transfer.
PRODUCTION FACCILITIES:Injection preperation area is the most sterilized area in Pharmaceutical industry because it is very sensitive in nature and as it has a direct contact with blood so high accuray and sterlity is consider during manufactoring.
STIMULLATION:It is the process in which we validate aseptic filling procedure. In stimulation two types of filtration are used. Air filteration Water filteration (a) AIR FILTERATION: Air is one of the greatest potential sources of contamination in clean rooms, so it is being drawn in to clean rooms by heating, ventilating & air conditioning (HVAC) system.This may be done by a series of treatments that will vary somewhat from one installation to another. HVAC SYSTEM: The HVAC system brings outdoor air into a building, humidifies or dehumidifies it, and heats or cools it to meet the ventilation and thermal comfort needs of the occupants and to dilute the contaminants inside the building. .A typical HVAC system consists of a supply air system, a return air system, and an exhaust air system. It generally also contains heating and cooling units, a humidifier, air filters, and fans, which treat and move the air. Controls are used to ensure that the system functions as desired.
Supply air is a mixture of outdoor air and return air (recirculated air) that is treated, conditioned, and supplied to the room by the HVAC system. Return air is air from the room that is recirculated into the mixing chamber by the HVAC system. Exhaust air is the air from the room that is exhausted from the building by the HVAC system. Functions: Heating is significant in maintaining adequate room temperature especially during colder weather conditions. Furnace or boiler, heat pump, and radiator make up the heating system. Ventilation is associated with air movement. Ventilation is necessary to allow carbon dioxide to go out and oxygen to get in, making sure that people are inhaling fresh air. Stagnant air causes the spreading of sickness, usually airborne, and allergies. Air-conditioning system controls the heat as well as ventilation.
WORKING: The air coming from HVAC system is passed through the PRE FILTER, usually of glass wool, cloth or shredded plastic, to remove large particles.
After passing through pre filter the air is than pass through the most efficient cleaning device, a HEPA filter. The clean, aseptic air is introduce into the class 100 area and maintained under positive pressure, which prevents outside air from rushing into the aseptic area through cracks, temporarily open doors or other openings. HEPA FILTERS:
The required environmental control of aseptic areas has been made by the use of laminar air flow, originating through a HEPA filter. Laminar Airflow: Unidirectional airflow moving along parallel flow lines at a constant velocity minimizes air turbulence within the work area. HEPA (high efficiency particulate air) filters are air filters that remove particles from the air by forcing air through screens with microscopic pores. HEPA filters are capable of removing 99.97 percent of the particles that are 0.3 microns or larger from the air. It must allow, on average, only 3 particles out of every 10,000 to pass through the filter. This means a HEPA filter is very effective at filtering out allergens and asthma triggers (e.g., dust, pollen, mold, dander, tobacco smoke). CONSTRUCTION: HEPA filters are composed of a mat of randomly arranged fibers. The fibers are typically composed of fiberglass and possess diameters between 0.5 and 2.0 micron. Key factors affecting function are fiber diameter, filter thickness, and face velocity. The air space between HEPA filter fibers is much greater than 0.3 m. WORKING: The common assumption that a HEPA filter acts like a sieve where particles smaller than the largest opening can pass through is incorrect. HEPA filters are designed to target much smaller pollutants and particles. These particles are trapped (they stick to a fiber) through a combination of the following three mechanisms: INTERCEPTION: where particles following a line of flow in the air stream come
within one radius of a fiber and adhere to it. IMPACTION: where larger particles are unable to avoid fibers by following the
curving contours of the air stream and are forced to embed in one of them directly; this effect increases with diminishing fiber separation and higher air flow velocity. DIFFUSION: an enhancing mechanism is a result of the collision with gas molecules by the smallest particles, especially those below 0.1 m in diameter,
which are thereby impeded and delayed in their path through the filter; this behavior is similar to Brownian motion and raises the probability that a particle will be stopped by either of the two mechanisms above; it becomes dominant at lower air flow velocities.
WATER FOR INJECTION:Water for injection is apyrogenic distilled water intended for use in the preparation of medicines for parenteral administration when water is used as a vehicle and dissolving or diluting substances or preparations for injectable preparation. GENERAL CONCEPT STRUCTURE:Potable water or Purified water Distillation unit Water for Injection
PREPARATION OF WATER FOR INJECTION: Take sufficient quantity of potable or purified water in a metal water still or glass distillation unit of neutral glass. Boil the water using burner or electricity. Allow to form sufficient steam. Steam is condensed to water for injection using water condenser by distillation unit. The first 50 ml portion of distillate is discarded and remainder is collected in a suitable borosilicate container. Rinse the container with water for injection and then reject that water for injection. Continue the process and collect the distillate in a suitable borosilicate container. The ph of water for injection must be 5-7.
CHECK OF WATER BEFORE USE:
Conductance test Ph test Chloride test.
PRODUCTION OF INJECTION:The preparation step should be done to prepared injection which are as follow: Line clearence. Dispensing. Washing of injection bottels. Compounding. Filling of injection. Leak test. Optical test. Packaging area. PCI section.
LINE CLEARENCE:Line clearance is check by worker, supervisor as well as PCI i.e Production Control Inspector. The line clearance include following steps: Check pressure, temperature as per SOP requirement. Check gas protection where required. Check the equipment/area is cleaned. Check no identity sign from previous batch. Check required commodities of the batch area available as per finishing shop order. Check exhaust are operational in powder filling. Check product name and strength on almonium foil.
DISPENSING:It is the first step of process and carried out in warehouse, dispensing is the process of weighing of raw materials.
WASHING & STERILIZATION OF EMPTY AMPULS AND VIALS:Ampoules and vials are washed mechanically by means of machines. For this purpose two types of machines are used Compact line machine. Abbott local machine. COMPACT LINE MACHINES:
It is automatic in which washing, sterilization, filling and sealing is done simultaneously. In Abbott it is set for the washing of 3ml ampoules. These machines have many features such as: water spraying, alternating water and compressed air flushing, drying, sterilizing, cooling, filling, gas flushing, sealing etc. It adopts photoelectric technology, PLC and color touch LCD screen for the control system. With such a high degree automation, fewer operator needed to use this machine. In order to meet the GMP requirements, laminar air flow above the filling and sealing machine is included. In order to meet the GMP requirements, laminar air flow above the filling and sealing machine is included. This line is highly flexible, can be used for 1 to 5 ml ampoules, with few parts needed to be replaced. This line is the highest output ampoule compact line in the world at present. Main applications
This line is highly flexible, can be used for 1 to 5 ml ampoules, with few parts needed to be replaced. This line is the highest output ampoule compact line in the world at present.
Pressurized flow of water is passed through washing needle for pressure cleaning at minimum usages of washing machine. Concept of pressure tanks for reverses & continuous supply of washes medias is apt in this machine. Acrylic top cover is given, to clearly view washing events taking place in the machine. On-line poly carbonates of 10 microns for water and 5 microns for air are used, for best possible washing. All contact parts of washing machine are usually made of stainless steel. If acrylic cover is lifted during cycle operation, the machine will automatically stop and re-start from the point when cover is pushed down. Output capacity of 300 Ampoules / min. Pressure of Water and Air is not less than 17 psi.
STEPS OF WASHING: 1. Ampoule first wash with recycled distilled water 2. Compressed Air 3. Distilled Water 4. Compressed Air . STERILIZATION: After washing ampoules enter into the sterilizing chamber (OVEN).Dry heat sterilization is occur at 335C for 1 hr.
ABBOTT LOCAL MACHINE:
The machine is designed for washing of ampoule and vials.
STEPS OF WASHING: 1. Compressed Air 2. Tap Water 3. Tap Water 4. Tap Water 5. Compressed Air 6. Distilled Water 7. Distilled Water 8. Compressed Air Pressure of Water and Air is 10 psi.
STERILIZATION: Ampoules or vials are sterilized in OVEN at 210 220C, time is 5 hrs.
COMPOUNDING:The second step is formulation and solution preparation .Solutions are not standardized but prepared in batch manufacturing using sterile water. Preparation occur in DOUBLE JACKETED PRESSURE VESSEL made up of STAINLESS STEEL (non reactive, easy to clean, no growth of microorganism), mixing occur by means of PROPELLER. All equipment must be dry and sterile, follow established order of mixing (MANUFACTURING ORDER),For parenteral preparation maintain proper reduction of particle size under aseptic conditions, Distilled water used as solvent should be kept and stores at 60 80C and used with in 24 hrs. It is done in compounding area. BATCH REACTOR: Within the chemical and pharmaceutical industries, external cooling jackets are generally preferred as they make the vessel easier to clean. The performance of these jackets can be defined by 3 parameters:
Response time to modify the jacket temperature Uniformity of jacket temperature Stability of jacket temperature
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