CHAPTER – II

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2.0 REVIEW OF LITERATURE

� Basavaraj K. Nanjawade [6] et.al, 2007 had studied the response of

environmental change on developed insitu forming hydrogels which upon

administration in cul-de-sac undergoes phase transition. In the past few years,

for sustained ophthalmic drug delivery polymers like temperature, ion and pH

induced are used for insitu gel forming systems.

� Katarina Edsman [57] et.al, 1998 had studied on the rheological properties of

the polymers and their measurements in ocular residence times in humans. sol–

gel transition temperature was studied.

� Veena S. Belgamwa [123] et.al, 2009 author studied on anti-emetic drug

Dimenhydrinate and its formulation using gellan gum and carbopol 934P and its

evaluated by properties like gelation, viscosity, gel strength, mucoadhesion,

drug content, drug diffusion, ex vivo permeation and histophathological studies.

� ZAKI Noha M [136] et.al, 2007 study reveals enhancement of drug release

with use of poloxamer and polyethylene glycol (PEG). The effect of

mucoadhesive polymer with PEG decreases the gel consistency and increases

the drug release. The formulation was stable upon storage.

� Miyazaki S [108] et.al, 2001 has studied the sustained release pilocarpine

hydrochloride formulated with thermo reversible gels for ocular delivery. The

study concluded that the increase in concentration of xyloglucan increases the

miotic response.

� Lin HR [66] et.al, 2000 studied the rheological properties of pH sensitive

polymers like carbopol and temperature responsive polymers like pluronic and

combination thereof. Author concluded from his study that obtained with

mixture of carbopol and pluronic solution with 0.3% and 14% enhances the gel

strength.

� Mayol L [75] et.al, 2008 revealed the gelation properties of poloxamer on

hyaluronic acid (HA). By using specific concentration of Poloxamer/HA, it was

possible to obtain a thermo reversible gel. The hyaluronic acid does not change

the process of gelation temperature. Poloxamer rheological properties increased

due to hyaluronic acid.

� Zhidong Liu [137] 2006 studied on conventional ophthalmic solutions and

observed elimination of the drug through precorneal membrane. Hence

developed a formulation using Alginate and HPMC as gelling agent and

viscosity enhancing agent respectively.

� Samdar Cohen [102] et.al, 1997 studied that bioavailability of ophthalmic

solution can be increased by avoiding lacrimal drainage. They demonstrated

without cationic sodium alginate solution (G content) can gel in the eye.

Worked on Pilocarpine drug and extended the release of drug. The overall study

concludes that polymer with high G content can prolong the delivery of drug

system.

� Jitendra Shinde [51] et.al, 2008 had worked on prolonged residence of drug

Metoclopramide HCl formulation in nasal cavity by formulating it with

Poloxamer and sodium alginate which helped in reduced nasal mucocilliary

clearance in order to improve bioavailability.

� Kun Na [60] et.al, 1997 studied and formulated the Indomethacin delivery

system using pullulan which response to pH. Also measured the swelling

capacity of pullulan acetate at different pH.

� Yoshie Maitani [134] et.al, 1997 work presented on ocular, nasolacrimal duct

and nasal route with drug/peptide absorption and administration. A first order

absorption process is based on factors like fast absorption and retention of drug

in the blood.

� Indu Pal Kaur [42] et.al, 2002 the study reveals on combining the two

approaches like bioadhesive polymers and penetrative enhancers that would

considerably prolong the release and contact time.

� FV Manvi [71] et.al, 1997 they worked on Timolol Maleate an anti glaucoma

drug to sustained the delivery and reduce the possible side effects. Formulated

circular ocular inserts by solvent casting, using cellulose acetate as polymer.

� Jennifer J. Kang [47] et.al, 2008 had worked on proteins that were

encapsulated into hydro gels and the release was adjusted by varying degree of

cross-linker. The use of thermo sensitive polymer for phase transition and

release of drug was studied.

� Deepika Aggarwal [16] et.al, 2005 present study focused on comparison of

coated niosomal Timolol Maleate and Timolol solution in terms of IOP

lowering effect. Chitosan and Carbopol were used for coating. It was concluded

that Chitosan coated formulation was lowering the IOP (20-40%) as compared

with the Timolol solution in the contralateral eye.

� Suketu D. Desai [113] et.al, 1998 developed controlled release ocular delivery

formulation containing Pluronic F127 using Pilocarpine HCl. Additives such as

PEG4600, PVP10000, PVA 10000, MC 15cp and HPMC 80 -120cp. 25%

concentration of PF127 was effective with 3% HPMC or 5% MC gave

promising dissolution results.

� Sankar Chelladurai [104] et.al, 2008 developed a gelling system of ketorolac

tromethamine which act as non narcotic analgesic. Chitosan and pectin were

used as gelling system with optimized concentric range. They concluded the

formulation prepared was able to provide better deposition, distribution and

residency properties.

� J.Balasubramaniam [45] et.al, 2003 formulated ion activated insitu gelation

on Indomethacin as NSAID. Use of gelrite gum provides 8 hours sustained

release in the lacrimal fluid. Thus formulated system provides sustained release

of the drug coupled with less frequent administration which enhances patient

compliance.

� J.Varshosaz [44] et.al, 2008 studied to increase the low bioavailability and

short ocular residence time of ciprofloxacin eye drops, aqueous solutions of

drug in Chitosan and Pluronic were prepared to identify suitable composition

with regards to gel forming properties and drug release. The membrane less

dissolution studies were carried out and release behavior was found till 8 hours.

� Witold Musial [128] 2007 proposed the treatment on acne rosacea by

composing various acrylic acid polymers with methylcellulose and studied

release rate of Metronidazole from hydrogels. Use of excipient like Carbopol

and methylcellulose vealed an increase in viscosity.

� Armand B. Pepperman [3] et.al, 1991 observed that similar release rates of

Metribuzin obtained from various grades and types of sodium alginates. On

further trials concluded that the 1% charcoal is used for irreversible adsorption

of release of Metribuzin with less than 10%.

� A.H.El-Kamel [19] et.al, 2002 aimed to enhance ocular bioavailability with

Pluronic. The rheological properties were studied of isotonic agent on

Poloxamer was studied. Formulation containing 3% methylcellulose and low

concentration of poloxamer showed improved ocular bioavailability.

� Yanxia Cao [131] et.al, 2007 investigated cloud point method was used to

determined Low critical solution temperature. The copolymer had a LCST of

320c which is close to eye temperature according to author. The copolymer had

little cytotoxicity of PNIPAAm-CS copolymer.

� Kouji Nakamura [58] et.al, 1999 studied and investigate the pharmacokinetic

of Budesonide. The copolymer exhibit pH and mucoadhesive properties. The

fickian kinetics was showed at initial burst.

� Sandeep Kuma [103] et.al, 1995 the study was to use an aqueous solution

containing a viscosity enhancing polymer. The rheological characterization and

invitro TM release profile demonstrates suitability of the HPMC-PAA

polymeric solutions in situ gelling drug delivery system.

� Tanaji Nandgude [117] et.al, 2008 prepared nasal solution of Salbutamol

sulphate with sustained release and improved bioavailability. Sol to gel

conversion of the formulation was induced by carbopol. The rheological

properties were determined and drug release was determined. The final

formulation was optimized with specific concentration of Carbopol 934 and

HPMC showed pH induced sol-gel conversion, sustained release and higher

bioavailability.

� Yeshwant D. Sanzgiri [132] et.al, 1993 they studied on application of MP ester

of gellan to sustain MP delivery to the eye. To improve bioavailability use of

gellan gum in conventional therapy provides a simple and effective way.

� Masahiro Irie [74] 1990 developed and studied effect of artificial

photoresponsive polymeric system. Aqueous solutions of poly (N -

isopropylacrylamide) with pendant azobenzene chromophores which resulted in

photostimulated phase separation on exposure to ultraviolet light.

� KS Soppimath [59] et.al, 2002 has provided a brief article on introduction and

recent development and applications of stimulus responsive hydrogels. The

polymers particularly temperature and pH responsive were revealed.

� Rein V Ulijn [94] et.al, 2007 has highlighted on recent development and

application in bioresponsive drug delivery system used in field of diagnostics

and tissue regeneration. Bioresponsive hydrogels have significant interest in

biosensing and which shows change in properties to selective biological events.

� Indrajeet D. Gonjari [41] et.al, 200 the study concluded that a fabricated

fluconazole formulation had thermo reversible polymers and mucoadhesive

polymers to prolong residence time.

� Priya Bawa [88] et.al, 2009 had reviewed the on different drug delivery system

in stimuli sensitive polymers. This innovative delivery system has achieved

steadily momentum and better application in pharmaceutical industries.

� Jing-Ji Xuan [50] et.al, 2010 studied the rheological characterization of

thermosensitive hydrogels, gels are prepared by cold method and

pharmacokinetics was investigated after its intramuscular administration to

rabbit.

� Wen-Di Ma [126] et.al, 2008 investigated the rheological properties and invitro

release of pluronic copolymer gel. The decreased drug release rate indicated by

molar ratio of acrylic acid/pluronic and their co polymeric solution

concentration which increase has depicted in rheogram and invitro studies.

� David S Jones [14] et.al, 2009 developed and evaluated formulation

comprising of different ratio of poloxamer and poly (acrylic acid). The physic-

chemical properties for the formulation were evaluated for binary polymeric

system.

� Hongyi Qt [27] et.al, 2006 developed an ophthalmic gel containing puerarin.

The prepared polymeric solution is a free flowing liquid below the room

temperature and shift to a gel upon exposure. The formulation was also

investigated for influence of the other ingredients on the physiological

properties.

� C S Satish [11] et.al, 2009 had reviewed on present investigation in hydrogels.

Its various methods of preparation of hydrogels, cross linking methods used in

the hydrogels preparation, the mechanism of water transport through the ionic

hydrogels, and the solute release mechanism from the hydrogels.

� Wei Wua [125] et.al, 2011 had studied a series of pH sensitive polymeric drug

delivery system. The polymeric network was structured by poly (vinyl alcohol)

PVA and 21-arm star poly[2-(dimethylamino)ethyl methacrylate] with different

molecular weight. Model drug riboflavin was used to evaluate the drug loading

capacities and drug release behaviors.

� Themis R. Kyriakides [118] et.al, 2002 had studied release behavior of drugs

from the acidic endosomal compartment to the cytoplasm through pH sensitive

membrane. Based on further investigation on hemolysis studies they found that

polymer particularly, poly (propylacrylic acid) (PPAA) is effective below pH6.5

for membrane disruption.

� Debashish Roy [15] et.al, 2010 had reviewed polymers which trigger with

sensitivity. A nanocomposite of cellulose nanofibers was embedded in a rubbery

ethylene oxide-epichlorohydrin copolymer was prepared to mimic the sea

cucumber dermis known to be composed of rigid collagen fibrils embedded

within a viscoelastic glycoprotein matrix.

� Sumit Chhabra [114] et.al, 2007 developed formulations from polymer with

carboxylic acid groups containing ester end groups showed release (4%).

However, formulations consisting of polymer with carboxylic acid end groups

incorporated with lysozyme showed faster release rate.

� Saurabh Gupta [106] et.al, 2010 studied the influence of poloxamer 407 by

manufacturing and stabilizing the Forskolin nanocrystals. The particle size of

nanocrystals was characterized by scanning electron microscopy and dynamic

light scattering.

� Daniel Wandera [12] et.al, 2010 review provides an understanding of stimuli

sensitive membranes. They examined significant importance and rapidly

developing field of stimuli responsive membrane. The bioresponsive can be

controlled by membrane material structured, factors and external stimuli like

pH, temperature and light.

� Majeti N.V. [68] et.al, 2000 the purpose of this review is to focus on chitin and

chitosan applications to solve numerous problems in environmental and

biomedical engineering.

� Jianwei Liu [49] et.al, 2010 hydrogels were prepared using UV and visible

light initiating photo polymerization technology. Studies were conducted on

swelling properties o both hydrogels and the behavior of ribavirin was also

determined on it. It was concluded that fabrica tion of photo responsive

hydrogels provide a novel path to design medical materials.

� Martien A. Cohen Stuart [73] et.al, 2010 article focuses on stimuli-responsive

conformation and chemical changes macromolecular nanostructures. The

changes is derived by temperature, change in chemical composition and

mechanical forces applied. Finally, challenges in theory and modeling of these

complex systems and future prospective are examined.

� Shimoboji [121] et.al, 2002 studied the polymeric chain coil to study photo

induced changes in the size and hydration.

� Nirmal H.B. [82] et.al, 2010 review discuss on formulation and development

different strategies for insitu drug delivery. The study reveals factors like

physiochemical and formulation factors affect the insitu gelling. Formulation

discussed on characteristics of polymeric systems.

� N.A. Peppas [80] et.al, 2000 reviewed on recent development of novel

pharmaceuticals which finds applications in biomedical carriers. A key role in

their diffusional behavior is played by network structure of components.

� Murat Sen [79] et.al, 2000 prepared hydrogels by direct adsorption method

using different polymer ratios with anti fungal drugs. The effect of gel matrix

was studied by influence of gel on Terbinafine. The hydrogels containing

factors like pH and MA content affects the drug release.

� Fiore Pasquale Nicoletta [23] et.al, 2012 briefly reports the progress of light-

driven materials and membranes. Discussed on light responsive polymer

membrane used in biotechnology, chemistry and biology areas.

� Jason A. Burdick [55] et.al, 2010 revealed on biomaterials in the field of light

responsive polymers. The light-responsive biomaterials upon exposure to light

undergoes chemical change in polymeric network which was used in

investigation multi-component surface patterning for advanced cell assays and

macromolecular assemblies for drug delivery.

� Joseph Kost [54] et.al, 2001 discussed on controlled drug delivery systems

used under responsive polymers. Thus adjusting the drug release rate as per

physiological need.

� Hana Krakovicova [29] et.al, 2009 studied new type of conjugates which

were synthesis using HPMA copolymers as drug carriers. Combination of two

drugs anti-inflammatory and anti-cancer drug or a combination of two anti-

cancer drugs, DOX and DEX were studied.

� Dirk Schmaljohann [17] 2006 reviewed on advances in stimuli sensitive

polymeric drug delivery systems. Multiple responses at the desired point of

action were studied.

� Soo-Chang Song [119] et.al, 2011 Investigated temperature sensitive hydrogels

after linking with photo sensitive polymer to improve mechanical properties. In

vitro and in vivo degradation rates of thermosensitive and photo -cross-linkable

poly (organophosphazenes) containing various amounts of isoleucine ethyl

ester, AMPEG550, AMPEG750, aminoethyl methacrylate and depsipeptide was

studied.

� Lalit kumar [62] et.al, 2011 study states that to reduce administration

frequency of dosing, prolong action of drug effect of insitu gel is provided by

sol- gel transition. Improved ocular bioavailability is obtained due to duration of

contact with corneal tissue.

� Anil K. Anal [1], 2007 article described in details on pulsed or triggered release

drug delivery systems of bioactive compounds due to certain external stimuli. A

new approach for medical and pharmaceutical scientists has developed on

triggered by thermally, electrically and magnetically induced release.

� M.R.Aguilar [78] et.al, 2007 article presented on bio responsive polymers like

temperature, pH and ion sensitive polymers. Author also revealed on recent

applications of these polymers in drug delivery.

� M.B. Brown [100] et.al, 2002 developed gentamicin formulation by solvent

evaporation method. When compared with IV the gentamicin has poor

bioavailability when administered through nasal route as in solution and dry

powder. To obtain a high bioavailability and prolonged release of a drug

combination of HA and CH was used intranasally.

� Erik Bechgaard [56] et.al, 2002 the present study estimated the diazepam in

sheep nasal and to correlate this to earlier results in rabbits and humans.

Additional, to compare the absorption at various initial periods in the two

animal models and man, due to the importance of early absorption in emergency

treatment.

� Miqin Zhang [81] et.al, 2010 review reveals the unique cationic properties of

chitosan in hydrogels and degradation and mechanisms pattern in the body.

� Doo Sung Lee [8] et.al, 2008 study presents discussed on block copolymer

hydrogels that shows respond to temperature, pH or both st imuli and also

focused on modified thermosensitive block copolymers.

� Kabra [7] et.al, 1997 the invention is directed towards non-toxic, non-irritating

drug delivery vehicles. Upon instillation in the eye, thicken to form a gel

whereby the residence or contact time of the delivered drugs with ocular tissue

is increased.

� Rajan Bawa [92] et.al, 2001 the invention is directed towards ophthalmic

compositions which show sol-gel transition upon administration. The

compositions of the present contain xanthan gum. Xanthan gum gels upon

contact with eye due to interaction with lysozyme component of tear fluid. The

strength of the gel formed by xanthan gum upon contact with lysozyme is

dependent upon both pyruvate and acetate content of xanthan gum.

� Evangelos Manias [21] et.al, 2005 the invention relates to development and

optimization of temperature responsive polymers. Temperature sensitive

polymers which have applicability to drug delivery in cell adhesion control and

microflow control such as in micro-fluidic devices.

� Anna Gutowska [2], 2005 the invention discussed on linear random copolymer

of an [meth-] acrylamide derivative and a hydrophilic comonomer having a

thermally reversible gel or gelling copolymer. The linear chains having a

plurality of molecular weight cut off and a therapeutic agent.

� James L. Brown [46] et.al, 2006 the invention focuses on process for

manufacturing temperature sensitive polymers utilizing a heat transfer fluid

comprising hydrocarbon fluid selected form aliphatic hydrocarbons, alicyclic

hydrocarbons, aliphatic-or alicyclic-substituted aromatic hydrocarbons or

mixture. The hydrocarbon fluid having a boiling point form 220 0C to 255 0C

and a melting point less than 40 0C thus temperature sensitive polymers are

produced.

� Wilhelmus Everardus Hennink [127] et.al, 2008 the invention relates to

change in solubility characteristics of formulation comprising poly (N-(2-

hydroxypropyl) methacrylamide mono/di-lactate) interpolymer by incubation.

Change in water solubility characteristics of the polymer is modified in presence

of hydrolysable groups by modification effected by incubation process.

� Yuichi Mori [135] et.al, 1991 the invention relates to drug carrier provides a

temperature sensitive polymer chemically bonded to a drug. The drug carrier is

capable of releasing a drug continuously in the body. The drug carrier is a liquid

when administered and becomes solid in the body in which states it is capable

of releasing a drug continuously. The drug carrier has a lower LCST than

human body temperature.

� Tomiharu Hosaka [120] et.al, 1986 the temperature sensitive polymer

composition accordingly to the invention comprises a polyamide matrix

dispersing a mixture of a phenolic compound which has an alkyl group having

from 11 to 36 carbon atoms and a polycondensate of a phenolic compound and

an aldehyde. The mixture is generally present in the composition in an amount

of from 5 to30 parts by weight per 100 parts by weight of the polyamide matrix.

The mixing ratio of the phenolic compound having along chain alkyl group to

the polycondensate is in range of 1:5 to 5:1. In short the present invention is

characterized by the combination of the long chain alkyl group - bearing

phenolic compound and the polycondensate by which miscibility between the

phenolic compound and polyamide resins is improved by the action of

polycondensate, which is readily miscible with phenolic compound.

2.1 DRUG AND EXCIPIENT PROFILE

2.1.1 TIMOLOL MALEATE [130, 129]

Rationale for drug selection: Timolol Maleate is used for glaucoma therapy and

popularly given by sterile drops, Timolol Maleate tablets also proved their

ability in this selection. The drawback of the system is hepatic metabolism and

hence total bioavailability was found to be absent prepared drops showed their

ability by passing the metabolism and providing prolonger release. Using kind

of system will lead to decrease in administration dose and time intervals.

Name: Timolol Maleate

Chemical name: (-)-l-(tert-butylamino)-3- [(4-morpholino-l, 2, 5-thiadiazol-3-

yl)oxy]-2-propanol maleate (1:1) (salt).

Chemical structure:

Molecular formula: C13H24N4O3S•C4H4O4

Molecular weight: 432.50

pH: between 3.8 and 4.3 in a solution containing 20 mg/ml.

2.1.2 POLOXAMER [93, 86, 122]

Pluronic undergoes sol to gel transitions and the resulting gel shows an

enhancement of the residence time in both nasal and ophthalmic cavity.

Gelation of concentration of pluronic is well documented phenomenon liquid

crystalline micellar phase [96].

Non proprietary name: Poloxamer BP, Poloxamer USP/NF, Poloxamera PhEur.

Synonyms: Lutrol, Pluronic, Supronic

Chemical structure:

Category: Gelling agent, dispersing agent.

Molecular weight: 131.57

Congealing point: 510C

Melting point: 53-570C

Solubility: Freely soluble in ethanol, propanol and water.

Description: Poloxamer generally occurs as white, free flowing prilled granules

or as cast solids. They are practically odourless and tasteless.

2.1.3 CARBOPOL [37, 93]

Rationale for selection of carbopol: Carbopol was used as pH responsive

polymer in the formulation. The pH of tear fluid is 7.4; hence sol gel transition

can be expected in this case.

Non proprietary name: Carbomers, Carbomera, carbome

Synonyms: Acritamer, Acylic acid Carbopol, Carboxy polymethylene,

polyacrylic acid, pemulen.

Functional category: bio adhesive, emulsifying agent, release modifier agent

viscosity increasing agent.

Glass transition temperature: 100-1050C

Specific gravity: 1.41

Particle size: 0.2um in diameter, the flocculated powder particle average 2 -7 um

in diameter and cannot be broken down into the primary particles.

Use in concentration:

Use Concentration (%) Gelling agent 0.5-2.0 Emulsifying agent 0.1-0.5

The molecular weight o carbomer resins are theoretically estimated at 7*10 5 to

4*109. Estimated Mc values of 237600 g/mol for carbopol 941 and

104400g/mol for carbopol 940.

2.1.4 CHITOSAN [67, 91, 93]

Rationale for selection for chitosan: chitosan is polysaccharide with positive

charged linear polymers.

Studies demonstrated that a novel thermo sensitive PNIPAAm-CS may have

positive utilization in the efficacy, bioavailability and pharmacokinetics of

water soluble drugs meant for delivery in to eye such as timolol maleate.

Non proprietary formula: B.P. chitosan hydrochloride, Ph.Eur. chitosani

hydrochloridum.

chitosan is not one chemical entity but varies in composition depending on the

manufacturer. The degree of deacetylation is necessary to obtained a soluble

product must be greater than 80 -85%. Chitosan is commercially available in

several types and grades that vary in molecular weight by 10,000 – 10,00,000

and vary in deacetylation and viscosity.

Category: coating agent, disintegrant film forming agent, mucoadhesive

polymers, viscosity increasing agent.

Description: chitosan occurs as odor less a white or creamy-white powder

flakes. Fiber formation is quite common during precipitation and the chitosan

may look cotton like.

Density: 1.35-1.40 g/cm3

Solubility: practically insoluble organic solvent and neutral or alkalis solution

pH above 6.5. Chitosan dissolves in readily in dilute and concentrated amine

group of the polymers becomes protonated, resulting in a positive charge

polysaccharides. Solubility is also affected by addition of salts in solution. The

result of a salting out, which lead to precipitation of chitosan in solution. When

chitosan is in solution the repulsion between the deacetylated units and their

neighboring glucosamine units cause it to exist in an extended conformation.

2.1.5 XANTHAN GUM [39, 83, 93]

Non properitery name: Xanthangum xanthani gummi,

Synonyms: keltrol, xantural, vanzan

Chemical name: xanthan gum

Molecular weight: 2 x 106

Structural formula: The polymer backbone consist of four β-D-glucose units

linked at the 1 and 4 position and is therefore identical in structure to cellulose.

Trisaccharides side chains on alternating anhydroglucose units distinguish

xanthan gum cellulose.

Description: white color odorless powder.

Specific gravity: 1.600 at 250C.

2.1.6 SODIUM ALGINATE [93]

Rationale for selection of sodium alginate: Sodium alginate was used as ion

responsive polymer in the formulation. Since human eye tear fluid contains

calcium ion in case of glaucoma diseases. Thus with the help of calcium ion

phase transition can be expected.

Non proprietary name: Sodium alginate, Natrii Alginas

Synonyms: Algin, alginic acid, Protonal

Chemical name: Sodium alginate

Description: sodium alginate occurs as an odorless and tasteless, white to pale

yellowish-brown colored powder.

Solubility: Practically insoluble in ethanol, ether, chloroform and aqueous

solutions in which the pH is less than 3.

Use of sodium alginate:

Use Concentration (%) Creams 5-10

Stabilizers 1-3 Suspending agent 1-5

2.1.7 CARRAGEENAN GUM [31, 93]

Non properitary name: Carrageenan

Synonyms: chondrus extract, gelcarin, Hygum, irish moss extract, viscarin.

Functional category: emulsifying agent, gel base, stabilizing agent suspending

agent sustained release tablet, viscosity increasing agent.

Description: Carrageenan when extracted from the appropriate seaweed source

is a yellow brown to white coarse to fine powder. Solubility carrageenan is a

stable through hygroscopic, polysaccharide and should be store in a cool dry

place.

Application in pharmaceutical: carrageenan is used variety of non parental

dosage form including emulsion, gel, cream, eye drop, nasal drops and tablets.

Carrageenan gum generally used at ratio of 0.7% level w/w or less and provides

viscosity to liquid.

2.1.8 GUAR GUM [29, 34, 36, 93]

Solubility: Insoluble in ethanol.

Structural formula:

2.1.9 HYPROM

Non proprietary

Synonyms: meth

Functional categ

Coating agent,

binder, viscosity

Acidity / Alkali n

Specific gravity:

Incompatibilities

.since it is nonio

oraganics to form

2.1.10 DIMETH

Molecular Form

Average mass: 99

Flash Point: 71 0

Density: 0.962 g

Molecular struct

M ELLOSE [93]

names: Hypromellose, Hydroxypropylmethyl c

hocel, methylcellulose, propylene glycolether.

gory: Pharmaceutical excipients.

film former, rate controlling agent, stabilizin

y increasing agent, chars at 225-230 0C.

nity: pH = 5.5-8.0 for a 1% w/w aqueous solutio

: 1.26.

s: Hypromellose is incompatible with some o

onic, Hypromellose will not Complex with meta

m insoluble precipitates.

HYL ACRYLAMIDE [30]

mula: C5H9NO

99.131104 Dalton

0C (161F)

g/mL

ture:

cellulose

ng agent, tablet

on.

oxidizing agents

allic salts or ionic

2.1.11 BENZALKONIUM CHLORIDE [32, 93]

Molecular formula: [C6H5CH2N (CH3)2R] Cl

Molecular weight: 360

Category: antimicrobial preservative disinfectant, solubilizer, wetting agent.

Description: occurs as a white or yellows powder or thick gel flakes.

Hygroscopic soapy to touch and bitter in taste.

Functional category: Antimicrobial, preservative, antiseptic, disinfectant,

solubilizer, wetting agent.

Minimum inhibitory concentration of BKC:

Micro organism

MIC (µg/ml)

Clostridium hisolyticum 5 Clostridium oedematiens 5 Clostridium tetani 5 Escherichia coli 16 Pseudomonas aeruginosa 30 Salmonella paratyphi 16 Vibrio cholera 2