Powders are intimate mixtures of dry, finely divided drugs and/or chemicals that may be intended for internal or external use.

Advantages/Disadvantages

flexibility in compoundinggood chemical stabilityEase of administration

time-consumingnot well-suited to dispense unpleasant tasting, hygroscopic or deliquescent drugsinaccuracy of dose

Types

Medicated

Aerosol

Preparation

Weighing of ingredientsComminutingBlending or mixingWeighing of individual dose

Materials

Active ingredients

Packaging

Types of material used to pack/dispense divided powdersFoilplastic bag used for volatilevegetable parchment thin, semiopaque, moisture-resistantwhite bond without moisture-resistant propertiesGlassine glazed, transparent, moisture-resistant paper used for volatile to a certain extent

Waxed transparent-water-proof paper used for hygroscopic and volatile drugs

Seidlitz powder is the name with which is commonly known a medication composed by a mixture of tartaric acid, sodium bicarbonate, and potassium sodium tartrate, used as a mild cathartic by dissolving in water and drinking.After ingestion, the powder combines with gastric juices developing intestinal gases which are somewhat helpful in evacuating the bowels. This medication's name comes from the Seidlitz Saline Springs of Bohemia (now Sedlčany in the Czech Republic), which were rather famous in Europe at the time this medication was first marketed in the late 19th century, even though the foregoing laxative constituents do not represent those of the springs named.

Use of Each ingredient – act as acid and base which react in the presence of water to cause effervescence

Use of Preparation - mild cathartic/laxative

Appearance – white powder

Storage – store in air tight containers

Granules are prepared agglomerates of powdered materials, may be used per se for the medicinal value of their content or they may be used for pharmaceutical purposes, as in making tablets. Granules generally fall within the range of 4-12 sieve size

Preparation

Wet

– moistening of the powder/mixture, passing resulting paste thru a sieve, drying in trays by air or heating. Granules are periodically moved about to prevent adhesion

- Fluid bed processing in which particles are placed in a conical chamber and vigorously dispersed and suspended while a liquid excipient is sprayed

Dry

- Passing through a compactor and granulating machine- Slugging where the powder is compressed into slugs and then granulated to the desired size

Advantages/Disadvantages

Flow better than powders

More stable

Wetted faster

Decreased dissolution rate

Types

Effervescent granulated salts - prepared by dry/fusion method and wet method

Formulation

Citric acid 1

Tartaric acid 2

NaHCO3 3.4

Total 6.4

Use of Each ingredient – act as acid and base which react in the presence of water to cause effervescence

Use of Preparation – effervescent vehicle

Appearance – white granules

Storage – store in air tight containers

Tablets

A tablet is a pharmaceutical dosage form. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose. The excipients can include diluents, binders or granulating agents, glidants (flow aids) and lubricants to ensure efficient tabletting; disintegrants to promote tablet break-up in the digestive tract; sweeteners or flavours to enhance taste; and pigments to make the tablets visually attractive. A polymer coating is often applied to make the tablet smoother and easier to swallow, to control the release rate of the active ingredient, to make it more resistant to the environment (extending its shelf life), or to enhance the tablet's appearance.

The compressed tablet is the most popular dosage form in use today. About two-thirds of all prescriptions are dispensed as solid dosage forms, and half of these are compressed tablets. A tablet can be formulated to deliver an accurate dosage to a specific site; it is usually taken orally, but can be administered sublingually, buccally, rectally or intravaginally. The tablet is just one of

the many forms that an oral drug can take such as syrups, elixirs, suspensions, and emulsions. Medicinal tablets were originally made in the shape of a disk of whatever color their components determined, but are now made in many shapes and colors to help distinguish different medicines. Tablets are often stamped with symbols, letters, and numbers, which enable them to be identified. Sizes of tablets to be swallowed range from a few millimeters to about a centimeter. Some tablets are in the shape of capsules, and are called "caplets". Medicinal tablets and capsules are often called pills. This is technically incorrect, since tablets are made by compression, whereas pills are ancient solid dose forms prepared by rolling a soft mass into a round shape. Other products are manufactured in the form of tablets which are designed to dissolve or disintegrate; e.g. cleaning and deodorizing products.

Tabletting formulations

In the tablet-pressing process, it is important that all ingredients be fairly dry, powdered or granular, somewhat uniform in particle size, and freely flowing. Mixed particle sized powders can segregate during manufacturing operations due to different densities, which can result in tablets with poor drug or active pharmaceutical ingredient (API) content uniformity but granulation should prevent this. Content uniformity ensures that the same API dose is delivered with each tablet.

Some APIs may be tableted as pure substances, but this is rarely the case; most formulations include excipients. Normally, an pharmacologically inactive ingredient (excipient) termed a binder is added to help hold the tablet together and give it strength. A wide variety of binders may be used, some common ones including lactose, dibasic calcium phosphate, sucrose, corn (maize) starch, microcrystalline cellulose, povidone polyvinylpyrrolidone and modified cellulose (for example hydroxypropyl methylcellulose and hydroxyethylcellulose).

Often, an ingredient is also needed to act as a disintegrant to aid tablet dispersion once swallowed, releasing the API for absorption. Some binders, such as starch and cellulose, are also excellent disintegrants.

Small amounts of lubricants are usually added, as well. The most common of these is magnesium stearate and calcium stearate.

[edit] Advantages and disadvantages

Variations on a common tablet design, which can be distinguished by both color and shape

Tablets are simple and convenient to use. They provide an accurately measured dosage of the active ingredient in a convenient portable package, and can be designed to protect unstable medications or disguise unpalatable ingredients. Colored coatings, embossed markings and printing can be used to aid tablet recognition. Manufacturing processes and techniques can provide tablets special properties, for example, sustained release or fast dissolving formulations.

Some drugs may be unsuitable for administration by the oral route. For example, protein drugs such as insulin may be denatured by stomach acids. Such drugs cannot be made into tablets. Some drugs may be deactivated by the liver when they are carried there from the gastrointestinal tract by the hepatic portal vein (the "first pass effect"), making them unsuitable for oral use. Drugs which can be taken sublingually are absorbed through the oral mucosae, so that they bypass the liver and are less susceptible to the first pass effect. The oral bioavailability of some drugs may be low due to poor absorption from the gastrointestinal tract. Such drugs may need to be given in very high doses or by injection. For drugs that need to have rapid onset, or that have severe side effects, the oral route may not be suitable. For example salbutamol, used to treat problems in the pulmonary system, can have effects on the heart and circulation if taken orally; these effects are greatly reduced by inhaling smaller doses direct to the required site of action.

[edit] Tablet properties

Tablets can be made in virtually any shape, although requirements of patients and tableting machines mean that most are round, oval or capsule shaped. More unusual shapes have been manufactured but patients find these harder to swallow, and they are more vulnerable to chipping or manufacturing problems.

Tablet diameter and shape are determined by the machine tooling used to produce them - a die plus an upper and a lower punch are required. This is called a station of tooling. The thickness is determined by the amount of tablet material and the position of the punches in relation to each other during compression. Once this is done, we can measure the corresponding pressure applied during compression. The shorter the distance between the punches, thickness, the greater the pressure applied during compression, and sometimes the harder the tablet. Tablets need to be hard enough that they don't break up in the bottle, yet friable enough that they disintegrate in the gastric tract.

Tablets need to be strong enough to resist the stresses of packaging, shipping and handling by the pharmacist and patient. The mechanical strength of tablets is assessed using a combination of (i) simple failure and erosion tests, and (ii) more sophisticated engineering tests. The simpler tests are often used for quality control purposes, whereas the more complex tests are used during the design of the formulation and manufacturing process in the research and development phase. Standards for tablet properties are published in the various international pharmacopeias (USP/NF, EP, JP, etc.). The hardness of tablets is the principle measure of mechanical strength. Hardness is tested using a hardness tester. The units for hardness have evolved since the 1930s.

Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall.

Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsules.[citation needed]

[edit] Manufacturing

[edit] Manufacture of the tableting blend

In the tablet pressing process, the main guideline is to ensure that the appropriate amount of active ingredient is in each tablet. Hence, all the ingredients should be well-mixed. If a sufficiently homogenous mix of the components cannot be obtained with simple blending processes, the ingredients must be granulated prior to compression to assure an even distribution of the active compound in the final tablet. Two basic techniques are used to granulate powders for compression into a tablet: wet granulation and dry granulation. Powders that can be mixed well do not require granulation and can be compressed into tablets through direct compression.

[edit] Wet granulation

Wet granulation is a process of using a liquid binder to lightly agglomerate the powder mixture. The amount of liquid has to be properly controlled, as over-wetting will cause the granules to be too hard and under-wetting will cause them to be too soft and friable. Aqueous solutions have the advantage of being safer to deal with than solvent-based systems but may not be suitable for drugs which are degraded by hydrolysis.

Procedureo Step 1: The active ingredient and excipients are weighed and mixed.o Step 2: The wet granulate is prepared by adding the liquid binder–adhesive to the powder

blend and mixing thoroughly. Examples of binders/adhesives include aqueous preparations of cornstarch, natural gums such as acacia, cellulose derivatives such as methyl cellulose, gelatin, and povidone.

o Step 3: Screening the damp mass through a mesh to form pellets or granules.o Step 4: Drying the granulation. A conventional tray-dryer or fluid-bed dryer are most commonly

used.o Step 5: After the granules are dried, they are passed through a screen of smaller size than the

one used for the wet mass to create granules of uniform size.

Low shear wet granulation processes use very simple mixing equipment, and can take a considerable time to achieve a uniformly mixed state. High shear wet granulation processes use equipment that mixes the powder and liquid at a very fast rate, and thus speeds up the manufacturing process. Fluid bed granulation is a multiple-step wet granulation process performed in the same vessel to pre-heat, granulate, and dry the powders. It is used because it allows close control of the granulation process.

[edit] Dry granulation

Dry granulation processes create granules by light compaction of the powder blend under low pressures. The compacts so-formed are broken up gently to produce granules (agglomerates). This process is often used when the product to be granulated is sensitive to moisture and heat. Dry granulation can be conducted on a tablet press using slugging tooling or on a roll press called a roller compactor. Dry granulation equipment offers a wide range of pressures to attain proper densification and granule formation. Dry granulation is simpler than wet granulation, therefore the cost is reduced. However, dry granulation often produces a higher percentage of fine granules, which can compromise the quality or create yield problems for the tablet. Dry granulation requires drugs or excipients with cohesive properties, and a 'dry binder' may need to be added to the formulation to facilitate the formation of granules.

[edit] Granule lubrication

After granulation, a final lubrication step is used to ensure that the tableting blend does not stick to the equipment during the tableting process. This usually involves low shear blending of the granules with a powdered lubricant, such as magnesium stearate or stearic acid.

[edit] Manufacture of the tablets

Whatever process is used to make the tableting blend, the process of making a tablet by powder compaction is very similar. First, the powder is filled into the die from above. The mass of powder is determined by the position of the lower punch in the die, the cross-sectional area of the die, and the powder density. At this stage, adjustments to the tablet weight are normally made by repositioning the lower punch. After die filling, the upper punch is lowered into the die and the powder is uniaxially compressed to a porosity of between 5 and 20%. The compression can take place in one or two stages (main compression, and, sometimes, pre-compression or tamping) and for commercial production occurs very fast (500–50 msec per tablet). Finally, the upper punch is pulled up and out of the die (decompression), and the tablet is ejected from the die by lifting the lower punch until its upper surface is flush with the top face of the die. This process is simply repeated many times to manufacture multiple tablets.

Common problems encountered during tablet manufacturing operations include:

poor (low) weight uniformity, usually caused by uneven powder flow into the die poor (low) content uniformity, caused by uneven distribution of the API in the tableting blend sticking of the powder blend to the tablet tooling, due to inadequate lubrication, worn or dirty

tooling, and sub-optimal material properties capping, lamination or chipping. Such mechanical failure is due to improper formulation design or

faulty equipment operation. capping is also occurred due to high moisture content.

[edit] Tablet compaction simulator

Tablet formulations are designed and tested using a laboratory machine called a Tablet Compaction Simulator or Powder Compaction Simulator. This is a computer controlled device that can measure the punch positions, punch pressures, friction forces, die wall pressures, and sometimes the tablet internal temperature during the compaction event. Numerous experiments with small quantities of different mixtures can be performed to optimise a formulation. Mathematically corrected punch motions can be programmed to simulate any type and model of production tablet press. Initial quantities of active pharmaceutical ingredients are very expensive to produce, and using a Compaction Simulator reduces the amount of powder required for product development.

[edit] Tablet presses

The tablet pressing operation

An old Cadmach rotary tablet press

Tablet presses, also called tableting machines, range from small, inexpensive bench-top models that make one tablet at a time (single-station presses), with only around a half-ton pressure, to large, computerized, industrial models (multi-station rotary presses) that can make hundreds of thousands to millions of tablets an hour with much greater pressure. The tablet press is an essential piece of machinery for any pharmaceutical and nutraceutical manufacturer. Common manufacturers of tablet presses include Fette, Korsch, Kikusui, Manesty, IMA and Courtoy. Tablet presses must allow the operator to adjust the position of the lower and upper punches accurately, so that the tablet weight, thickness and density can each be controlled. This is achieved using a series of cams, rollers, and/or tracks that act on the tablet tooling (punches). Mechanical systems are also incorporated for die filling, and for ejecting and removing the

tablets from the press after compression. Pharmaceutical tablet presses are required to be easy to clean and quick to reconfigure with different tooling, because they are usually used to manufacture many different products.

[edit] Tablet coating

Many tablets today are coated after being pressed. Although sugar-coating was popular in the past, the process has many drawbacks. Modern tablet coatings are polymer and polysaccharide based, with plasticizers and pigments included. Tablet coatings must be stable and strong enough to survive the handling of the tablet, must not make tablets stick together during the coating process, and must follow the fine contours of embossed characters or logos on tablets. Coatings are necessary for tablets that have an unpleasant taste, and a smoother finish makes large tablets easier to swallow. Tablet coatings are also useful to extend the shelf-life of components that are sensitive to moisture or oxidation. Special coatings (for example with pearlescent effects) can enhance brand recognition.

If the active ingredient of a tablet is sensitive to acid, or is irritant to the stomach lining, an enteric coating can be used, which is resistant to stomach acid, and dissolves in the less acidic area of the intestines. Enteric coatings are also used for medicines that can be negatively affected by taking a long time to reach the small intestine, where they are absorbed. Coatings are often chosen to control the rate of dissolution of the drug in the gastrointestinal tract. Some drugs will be absorbed better at different points in the digestive system. If the highest percentage of absorption of a drug takes place in the stomach, a coating that dissolves quickly and easily in acid will be selected. If the rate of absorption is best in the large intestine or colon, then a coating that is acid resistant and dissolves slowly would be used to ensure it reached that point before dispersing.

There are two types of coating machines used in the pharmaceutical industry: coating pans and automatic coaters. Coating pans are used mostly for sugar coating of pellets. Automatic coaters are used for all kinds of coatings; they can be equipped with remote control panel, dehumidifier, dust collectors. The explosion-proof design is required for alcohol containing coatings.

ASA Tablet

Ingredients - active ingredient acetylsalicylic acid, corn starch, water, and a lubricant.

Raw Materials

To produce hard aspirin tablets, corn starch and water are added to the active ingredient (acetylsalicylic acid) to serve as both a binding agent and filler, along with a lubricant.

Binding agents assist in holding the tablets together

Fillers (diluents) give the tablets increased bulk to produce tablets of adequate size.

Lubricant keeps the mixture from sticking to the machinery. A portion of the lubricant is added during mixing and the rest is added after the tablets are compressed Possible lubricants include: hydrogenated vegetable oil, stearic acid, talc, or aluminum stearate. Scientists have performed considerable investigation and research to isolate the most effective lubricant for hard aspirin tablets.

Chewable aspirin tablets contain different diluents, such as mannitol, lactose, sorbitol, sucrose, and inositol, which allow the tablet to dissolve at a faster rate and give the drug a pleasant taste. In addition, flavor agents, such as saccharin, and coloring agents are added to chewable tablets. The colorants currently approved in the United States include: FD&C Yellow No. 5, FD&C Yellow No. 6, FD&C Red No.3, FD&C Red No. 40, FD&C Blue No. 1, FD&C Blue No. 2, FD&C Green No. 3, a limited number of D&C colorants, and iron oxides.

The Manufacturing Process

Aspirin tablets of the same dosage amount are manufactured in batches. After careful weighing, the necessary ingredients are mixed and compressed into units of granular mixture called slugs. The slugs are then filtered to remove air and lumps, and are compressed again (or punched) into numerous individual tablets.

The procedure for manufacturing hard aspirin tablets, known as dry-granulation or slugging, is as follows:

Weighing

The corn starch, the active ingredient, and the lubricant are weighed separately in sterile canisters to determine if the ingredients meet pre-determined specifications for the batch size and dosage amount.

Mixing

The corn starch is dispensed into cold purified water, then heated and stirred until a translucent paste forms. The corn starch, the active ingredient, and part of the lubricant are next poured into one sterile canister, and the canister is wheeled to a mixing machine called a Glen Mixer. Mixing blends the ingredients as well as expels air from the mixture.

The mixture is then mechanically separated into units, which are generally from 7/8 to 1 inches (2.22 to 2.54 centimeters) in size. These units are called slugs.

Dry screening

Next, small batches of slugs are forced through a mesh screen by a hand-held stainless steel spatula. Large batches in sizable manufacturing outlets are filtered through a machine called a Fitzpatrick mill. The remaining lubricant is added to the mixture, which is blended gently in a rotary granulator and sifter. The lubricant keeps the mixture from sticking to the tablet machine during the compression process.

Compression

The mixture is compressed into tablets either by a single-punch machine (for small batches) or a rotary tablet machine (for large scale production). The majority of single-punch machines are power-driven, but hand-operated models are still available. On single-punch machines, the mixture is fed into one tablet mold (called a dye cavity) by a feed shoe, as follows:

o The feed shoe passes over the dye cavity and releases the mixture. The feed shoe then retracts and scrapes all excess mixture away from the dye cavity.

o A punch—a short steel rod—the size of the dye cavity descends into the dye, compressing the mixture into a tablet. The punch then retracts, while a punch below the dye cavity rises into the cavity and ejects the tablet.

o As the feed shoe returns to fill the dye cavity again, it pushes the compressed tablet from the dye platform.

On rotary tablet machines, the mixture runs through a feed line into a number of dye cavities which are situated on a large steel plate. The plate revolves as the mixture is dispensed through the feed line, rapidly filling each dye cavity. Punches, both above and below the dye cavities, rotate in sequence with the rotation of the dye cavities. Rollers on top of the upper punches press the punches down onto the dye cavities, compressing the mixture into tablets, while roller-activated punches beneath the dye cavities lift up and eject the tablets from the dye platform.

Testing

The compressed tablets are subjected to a tablet hardness and friability test, as well as a tablet disintegration test (see Quality Control section below).

Bottling and packaging

The tablets are transferred to an automated bottling assembly line where they are dispensed into clear or color-coated polyethylene or polypropylene plastic bottles or glass bottles. The bottles are topped with cotton packing, sealed with a sheer aluminum top, and then sealed with a plastic and rubber child-proof lid. A sheer, round plastic band is then affixed to the circular edge of the lid. It serves as an additional seal to discourage and detect product tampering.

The bottles are then labeled with product information and an expiration date is affixed. Depending on the manufacturer, the bottles are then packaged in individual cardboard boxes. The packages or bottles are then boxed in larger cardboard boxes in preparation for distribution to distributors.

Quality Control

Maintaining a high degree of quality control is extremely important in the pharmaceutical manufacturing industry, as well as required by the Food and Drug Administration (FDA). All machinery is sterilized before beginning the production process to ensure that the product is not contaminated or diluted in any way. In addition, operators assist in maintaining an accurate and even dosage amount throughout the production process by performing periodic checks, keeping meticulous batch records, and administering necessary tests. Tablet thickness and weight are also controlled.

Once the tablets have been produced, they undergo several quality tests, such as tablet hardness and friability tests. To ensure that the tablets won't chip or break under normal conditions, they are tested for hardness in a machine such as the Schleuniger (or Heberlein) Tablet Hardness Tester. They are also tested for friability, which is the ability of the tablet to withstand the rigors of packaging and shipping. A machine called a Roche Friabilator is used to perform this test. During the test, tablets are tumbled and exposed to repeated shocks.

Another test is the tablet disintegration test. To ensure that the tablets will dissolve at the desirable rate, a sample from the batch is placed in a tablet disintegration tester such as the Vanderkamp Tester. This apparatus consists of six plastic tubes open at the top and bottom. The bottoms of the tubes are covered with a mesh screen. The tubes are filled with tablets and immersed in water at 37 degrees Fahrenheit (2.77 degrees Celsius) and retracted for a specified length of time and speed to determine if the tablets dissolve as designed.

Capsules

The powder or spheroids inside the capsule contains the active ingredient(s) and any excipients, such as binders (provide cohesion) , disintegrants (facilitate wetting and break up of contents in the stomach specially water-insoluble glidants ), fillers, glidant /lubricants , and preservatives.

In the manufacture of pharmaceuticals, encapsulation refers to a range of techniques used to enclose medicines in a relatively stable shell known as a capsule, allowing them to, for example, be taken orally or be used as suppositories. The two main types of capsules are:

Hard-shelled capsules, which are normally used for dry, powdered ingredients or miniature pellets (also called spheroids that are made by the process of Extrusion and Spheronization - Spheronization is a trade mark of Caleva Process Solutions) or tablets;

Soft-shelled capsules, primarily used for oils and for active ingredients that are dissolved or suspended in oil.

Both of these classes of capsules are made from aqueous solutions of gelling agents like:

Animal protein mainly gelatin; Plant polysaccharides or their derivatives like carrageenans and modified forms of starch and

cellulose.

Other ingredients can be added to the gelling agent solution like plasticizers such as glycerin and/or sorbitol to decrease the capsule's hardness, coloring agents, preservatives, disintegrants, lubricants and surface treatment.

Since their inception, capsules have been viewed by consumers as the most efficient method of taking medication. For this reason, producers of drugs such as OTC analgesics wanting to emphasize the strength of their product developed the "caplet" or "capsule-shaped tablet" in order to tie this positive association to more efficiently-produced tablet pills. After the 1982 Tylenol tampering murders, capsules experienced a minor fall in popularity as tablets were seen as more resistant to tampering.[1]

[edit] Manufacturing materials

Gelatin capsules, informally called gel caps or gelcaps, are composed of gelatin manufactured from the collagen of animal skin or bone. (Gelatin is not derivable from ungulate hooves, which are composed of a different protein, keratin.)

Vegetable capsules are composed of hypromellose, a polymer formulated from cellulose.

[edit] Manufacturing equipment

The process of encapsulation of hard gelatin capsules could be done on manual, semi-automatic and automatic machines. Softgels are filled at the same time as they are produced and sealed on the rotary die of fully automatic machine.

Standard sizes of two-piece capsules

Size Volume (ml)[A] Locked length (mm)[A] External diameter (mm)[A]

5 0.13 11.1 4.91

4 0.21 14.3 5.31

3 0.3 15.9 5.82

2 0.37 18 6.35

1 0.5 19.4 6.91

0 0.68 21.7 7.65

0E 0.7 23.1 7.65

00 0.95 23.3 8.53

000 1.37 26.14 9.91

13 3.2 30 15.3

12 5 40.5 15.3

12el 7.5 57 15.5

11 10 47.5 20.9

10 18 64 23.4

7 24 78 23.4

Su07 28 88.5 23.4

[edit] Two-piece gel encapsulation

Two-piece, hard starch capsules

http://en.wikipedia.org/wiki/File:Pharmacological_Capsule_Diclofenac_%C2%B5CT.jpg

Reconstruction from µCT-data of a hard starch capsule containing Diclofenac. Resolution 18,6 µm/pixel. Image acquisition was done using "CT Alpha" by "Procon X-Ray GmbH" from Garbsen, Germany. Analysis done using "VG Studio Max 2.0" by Volume Graphics, Heidelberg, Germany

Flight through the image stack of the above scan.

James Murdock of London patented the two-piece telescoping gelatin capsule in 1847.[2] The capsules are made in two parts by dipping metal pins in the gelling agent solution. Two-piece gelatin capsule machinery is manufactured by R&J Engineering Corporation of Canada. The capsules are supplied as closed units to the pharmaceutical manufacturer. Before use, the two halves are separated, the capsule is filled with powder or more normally spheroids made by the process of spheronization (either by placing a compressed slug of powder into one half of the capsule, or by filling one half of the capsule with loose powder) and the other half of the capsule is pressed on. With the compressed slug method, weight varies less between capsules. However, the machinery required to manufacture them is more complex.[3]

Routes of administration / Dosage formsOral

Digestive tract (enteral)

Solids

Pill Tablet Capsule Time

release technology

Osmotic controlled release capsule (OROS)

Liquids

Solution Softgel Suspension Emulsion Syrup Elixir Tincture Hydrogel

Buccal / Sublabial / Sublingual

Solids

Orally Disintegrating Tablet (ODT)

Film Lollipop Lozenges Chewing

gum

Liquids

Mouthwash Toothpaste Ointment Oral spray

Respiratory tract

Solids

Smoking device

Dry Powder Inhaler (DPI)

Liquids

pressurized Metered Dose Inhaler (pMDI)

Nebulizer Vaporizer

Gas

Oxygen mask

Oxygen concentrator

Anaesthetic machine

Relative analgesia machine

Ocular / Otologic / Nasal

Nasal spray Ear drops Eye drops Ointment Hydrogel Nanosphere suspension Mucoadhesive microdisc (microsphere tablet)

Urogenital

Ointment Pessary (vaginal suppository) Vaginal ring Vaginal douche Intrauterine device (IUD) Extra-amniotic infusion Intravesical infusion

Rectal (enteral)

Ointment Suppository Enema (Solution • Hydrogel) Murphy drip Nutrient enema

Dermal Ointment

Liniment Paste Film Hydrogel Liposomes Transfersome vesicals Cream Lotion Lip balm Medicated shampoo Dermal patch Transdermal patch Transdermal spray Jet injector

Injection / Infusion(into tissue/blood)

Skin

Intradermal Subcutaneous Transdermal

implant

Organs

Intracavernous Intravitreal Intra-articular

or intrasynovial injection

Transscleral

Central nervous system

Intracerebral Intrathecal Epidural

Circulatory / Musculoskeletal

Intravenous Intracardiac Intramuscular Intraosseous Intraperitoneal Nanocell

injection

Additional explanation:

Mucous membranes are used by the human body to absorb the dosage for all routes of administration, except for "Dermal" and "Injection/Infusion".

Administration routes can also be grouped as Topical (local effect) or Systemic (defined as Enteral = Digestive tract/Rectal, or Parenteral = All other routes).

[edit] Pill-splitters

It is sometimes necessary to split tablets into halves or quarters. Tablets are easier to break accurately if scored, but there are devices called pill-splitters which cut unscored and scored tablets. Tablets with special coatings (for example enteric coatings or controlled-release coatings) should not be broken before use, as this will expose the tablet core to the digestive juices, circumventing the intended delayed-release effect.

1. A small pellet or tablet of medicine, often coated, taken by swallowing whole or by chewing.

ilulae Ferri Carbonatis.—Pills Of Ferrous Carbonate, U. S. P.

These are popularly known as Blaud's pills. They consist of ferrous carbonate, potassium sulphate and sugar, with a smaller proportion of tragacanth and althea to make a mass. Each pill represents approximately 0.06 gm. or 1 grain of ferrous carbonate. They should be made fresh when wanted.

Dosage: 2 pills.

Ingredients Of Pills And How To Mass Them. Part 10

Fel Bovinum

The best excipient is a sufficiency of equal parts of tragacanth and acacia. The ox-gall may be bought in a dried and powdered state. In this condition it is very convenient, and forms an excellent mass with dec. aloes co. conc. Coat with keratin solution.

Ferri Bromidum

The Societe de Pharmacie de Paris recommends a hot strong solution of the bromide to be mixed in a dry warm porcelain mortar with liquorice-powder and gum arabic, in equal parts, sufficient to make a mass. The pills should be rolled in lycopodium or, better, coated with sugar, and preserved in a well-dried bottle.

Ferri Carbonas

The old-fashioned saccharated car-Donate of iron has now been largely displaced through the popularity of Blaud's pills. Five grains of the saccharated carbonate makes a good pill with 1 grain of theriacanth. The original Blaud's pill was made by heating together sulphate of iron and carbonate of potash in honey, then adding other ingredients, and evaporating to a pilular consistence. It is about thirty years since physicians in this country began to prescribe a similar combination of sulphate of iron with an alkaline

carbonate or bicarbonate. To the dispenser it mattered much whether carbonate or bicarbonate was ordered. Thus, with sodium carbonate (dried) the reaction is according to the following equation:

FeSO4,7H2O + Na2CO3 = FeCO8 + Na2SO4 + 7H2O.

With sodium bicarbonate it is as follows:

FeSO4,7H2O + 2NaHCO3 = FeCO3 + Na2SO4 + CO2 + 8H2O.

In the latter case the freed carbonic-acid gas greatly affects the resulting mass. Either the salts must be allowed to lie until all the gas is expelled (whereby the ferrous salt is much oxidised by exposure) and then massed, or the mass may be made right off, the consequence being that the pills are much larger than they should be, owing to occluded gas. It is apparent also that, owing to the liberation of water of crystallisation, soft excipients are inapplicable. About 1887 the pill had become so popular that the British Pharmaceutical Conference devised a formula which comprised most of the good points brought forward by dozens of pharmacists from time to time, and in due course the formula was introduced into the British Pharmacopoeia. It was improved in the 1898 and 1914 editions. We append the B.P.C. original and the B.P. 1914 formulae. The first gives a pill in which ferrous sulphate and potassium carbonate exist as such with some ferrous carbonate; the second provides a pill of ferrous carbonate:

B.P.C.

Ferrous sulphate.......... 60 gr.

Potassium carbonate .... . 36 ,,

Sugar, in powder ....... 12 „

Tragacanth, in powder 4 ,,

Glycerin ................... 2 1/2 min.

Distilled water .............a sufficient quantity

B.P.

Exsiccated ferrous sulphate (in powder).33 grm.

Exsiccated sodium carbo-

nate (in powder) . 21 ,,

Tragacanth (in powder) . 2 ,,

Acacia ,, ,, , 8 „

Glucose .... 31 ,,

Distilled water 2 ml.

The B.P.C. directions were: Reduce the sulphate of iron to fine powder, add the sugar and tragacanth, and mix intimately. Finely powder the carbonate of potassium in another mortar, and thoroughly incorporate with it the glycerin. Transfer this to the mortar containing the sulphate of iron, beat thoroughly

until the mass becomes green, add water sufficient to impart a soft pilular consistence, and divide into twenty-four pills.

The B.P. directions for making the pill are: Mix the ferrous sulphate with the glucose and water, add the sodium carbonate, mix, set aside for ten minutes to complete the reaction, and mass with the gums.

Cold cream is an emulsion of fats and water which can be used to clean and soften the skin. Traditionally, cold cream has been used to remove makeup gently at the end of the day, and it can also be used to soften tough skin on the knees and elbows, or to keep skin protected from harsh winter weather. Many drug stores and beauty suppliers sell cold cream, often in a variety of styles; different brands have different ingredients, and some people experiment with several before finding one which works.The concept of cold cream is quite ancient. Credit for the invention is usually given to Galen, a second century Greek physician who developed an emulsion of beeswax, oil, rose petals, and water. The cream was designed to moisturize and condition the face, and to help remove the harsh makeup of the period. In some regions, cold cream is called “cream of Galen” or “Galen's cream” in a reference to this; the “cold” in cold cream comes from the cool, refreshing feeling that it leaves behind.There are several ways to use cold cream. To remove makeup, a thin layer is spread on the face, allowed to sit for a moment, and then wiped off. Tissues or washcloths can be used to remove the cold cream. The moisturizing agents in the cream will condition the face and help it recover from harsh beauty products.

Advantages/Disadvantages

Types

Preparation

Materials

Packaging

Formulation

Use of Each ingredient

Use of Preparation

Dose

Appearance

Storage