59

CHAPTER -2

60

2.1 DRUG PROFILES

2.1.1 Drug Profile of Stavudine70

Description: White, amorphous powder and Hygroscopic

Category: Antiretroviral, Reverse Transcriptase Inhibitor(Nucleoside)

Structure:

Fig 2.1: Structure of Stavudine

Chemical Name: 1-((2R, 5S)-5-(hydroxymethyl)-2, 5-dihydrofuran-2-yl) -

5-methylpyrimidine-2, 4(1H, 3H)-dione

Molecular Formula: C10 H12 N2 O4

Molecular Weight: 224.2

Solubility: Soluble in water and sparingly soluble in Ethanol ( 95 % )

Storage: Store in a well closed container, protected from light

Specific Rotation: Between – 39.0o and -46.0o, determined in a 0.7%

W/V solution in water.

Sulphated Ash: Not more than 0.3%

Loss on Drying: Not more than 20 ppm, determined on 1.0 g by drying

at 105o for 3 hours.

61

PHARMACOLOGICAL ACTIONS

Mechanism of Action:

Stavudine is an analog of thymidine. It is phosphorylated by

cellular kinases into active triphosphate. Stavudine triphosphate inhibits

the HIV reverse transcriptase by competing with natural substrate,

thymidine triphosphate. It also causes termination of DNA synthesis by

incorporating into it.

PHARMACODYNAMICS/KINETICS:

Distribution: Vd: 46 L

Bioavailability: 86.4%

Metabolism: Undergoes intracellular phosphorylation to an active

metabolite

Half-life elimination: 1.2-1.6 hours

Time to peak, serum: 1 hour

Excretion: Urine (42% as unchanged drug)

2.1.2 Drug Profile of Lamivudine71

Description: white to off-white crystalline powder

Category: Antiretroviral, commonly called 3TC) is a potent nucleoside

analog reverse transcriptase inhibitor (nRTI)

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Structure:

Fig 2.2: Structure of Lamivudine

Chemical Name: L-2',3'-dideoxy-3'-thiacytidine; (2R, cis)-4-amino-1-(2-

hydroxymethyl-1 ,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one;

(-) 2',3'- Dideoxy- 3' -thiacytidine; 3TC; 3'-thia-2',3'-

dideoxcytidine;

Molecular Formula: C8H11N3O3S

Molecular Weight: 229.26

Solubility: Soluble in water and sparingly soluble in Ethanol ( 95 % )

Storage: Store in a well closed container, protected from light

Specific Rotation: Between – 39.0o and -46.0o, determined in a 0.7%

W/V solution in water.

Sulphated Ash: Not more than 0.3%

Assay: 98.0 - 102.0%

Residue on Ignition: 0.25% max

Loss on Drying: 0.5% max

Optical Rotation:-93° ~ -100°

Heavy Metals: 20ppm max

63

PHARMACOLOGICAL ACTIONS

Mechanism of Action:

Lamivudine is an analogue of cytidine. It can inhibit both types (1

and 2) of HIV reverse transcriptase and also the reverse transcriptase of

hepatitis B. It needs to be phosphorylated to its triphosphate form before

it is active. 3TC-triphosphate also inhibits cellular DNA polymerase.

Lamivudine is administered orally, and it is rapidly absorbed with a

bio-availability of over 80%. Some research suggests that Lamivudine can

cross the blood-brain barrier. Lamivudine is often given in combination

with Zidovudine, with which it is highly synergistic. Lamivudine

treatment has been shown to restore Zidovudine sensitivity of previously

resistant HIV. Several mutagenicity tests show that lamivudine should

not show mutagenic activity in therapeutic doses.

PHARMACOKINETICS:

Absorption:

Rapidly absorbed; bioavailability in adults and adolescents is 80 to

88% and in children is approximately 66 to 68% . Food delays the peak

serum concentration and the time to peak serum concentration; however,

there is no significant difference in bioavailability . Therefore, lamivudine

may be administered with or without food .

Distribution:

Lamivudine is widely distributed. Lamivudine crosses the blood-

brain barrier and is distributed into the cerebrospinal fluid (CSF) to a

limited extent . In children, CSF concentrations ranged from 10 to 17% of

the corresponding, non–steady-state serum concentration . Lamivudine

crosses the placenta in rats, rabbits , and humans .Apparent Vol D=

Approximately 1.3 liters per kg .

64

Protein binding: Low (36%).

Biotransformation:

Trans-sulfoxide is the only known metabolite of lamivudine; serum

concentrations of this metabolite have not been determined .

Half-life:

Adults: 2.6 ± 0.5 hours, Children (4 months to 14 years of age): 1.7 to 2

hours .

Time to peak concentration:

Approximately 0.5 to 2 hours after a single 100–milligram dose.

With food—Approximately 3.2 hours,

Fasting—Approximately 1 hour .

Peak serum concentration:

Adults and adolescents—2 mg per kg of body weight (mg/kg): 1.5

micrograms per mL (mcg/mL) (6.5 micromoles per liter).

Elimination:

Renal; the majority of lamivudine is eliminated unchanged in the

urine (68 to 71%) ; approximately 5.2% of the trans-sulfoxide metabolite

is excreted in the urine within 12 hours . The renal clearance of

lamivudine is greater than the glomerular filtration rate, implying active

secretion into the renal tubules.

2.1.3 Drug Profile of Ritonavir72

Description: white to light tan powder.

Category: Antiretroviral

Structure:

65

Fig: 2.3 Structure of Ritonavir

Chemical formula : C37H48N6O5S2,

Molecular Weight : 720.95

IUPAC Name:

2,4,7,12- tetra azatridecan- 13oic acid, 10 hydroxy- 2- methyl-

5- (1- methyl ethyl)- 1- [2- (1- methyl ethyl)- 4- thiazolyl]- 3,6- dioxo-

8,11- bis(phenyl methyl)- 5- thiazolmethyl ester

Solubility:

Freely soluble in methanol and ethanol, soluble in isopropanol

and practically insoluble in water.

Mol. Mass: 720.946 g/mol

Pharmacokinetic Data:

Protein binding: 98-99%

Half life: 3-5 hours

Bioavailability: 60%

Mechanism of Action:

Ritonavir is a peptidomimetic inhibitor of both the HIV-1 and HIV-2

proteases. Inhibition of HIV protease renders the enzyme incapable of

processing the gag-pol polyprotein precursor which leads to production of

non-infectious immature HIV particles.

66

Recommended Dosage

The recommended dosage of ritonavir is 600 mg twice daily by

mouth. Use of a dose titration schedule may help to reduce treatment-

emergent adverse events while maintaining appropriate ritonavir plasma

levels. Ritonavir should be started at no less than 300 mg twice daily and

increased at 2 to 3 day intervals by 100 mg twice daily.

Pharmacokinetics:

The pharmacokinetics of ritonavir have been studied in healthy

volunteers and HIV-infected patients (CD4 ≥ 50 cells/μL). See Table 1 for

ritonavir pharmacokinetic characteristics.

Absorption:

The absolute bioavailability of ritonavir has not been determined.

After a 600 mg dose of oral solution, peak concentrations of ritonavir

were achieved approximately 2 hours and 4 hours after dosing under

fasting and non-fasting (514 KCal; 9% fat, 12% protein, and 79%

carbohydrate) conditions, respectively.

Effect of Food on Oral Absorption:

When the oral solution was given under non-fasting conditions,

peak ritonavir concentrations decreased 23% and the extent of

absorption decreased 7% relative to fasting conditions.

Metabolism:

Nearly all of the plasma radioactivity after a single oral 600 mg

dose of 14C-ritonavir oral solution (n = 5) was attributed to unchanged

ritonavir. Five ritonavir metabolites have been identified in human urine

and feces. The isopropylthiazole oxidation metabolite (M-2) is the major

metabolite and has antiviral activity similar to that of parent drug;

however, the concentrations of this metabolite in plasma are low. In vitro

studies utilizing human liver microsomes have demonstrated that

cytochrome P450 3A (CYP3A) is the major isoform involved in ritonavir

metabolism, although CYP2D6 also contributes to the formation of M-2.

67

Elimination:

In a study of five subjects receiving a 600 mg dose of 14C-ritonavir

oral solution, 11.3 ± 2.8% of the dose was excreted into the urine, with

3.5 ± 1.8% of the dose excreted as unchanged parent drug. In that study,

86.4 ± 2.9% of the dose was excreted in the feces with 33.8 ± 10.8% of

the dose excreted as unchanged parent drug. Upon multiple dosing,

ritonavir accumulation is less than predicted from a single dose possibly

due to a time and dose-related increase in clearance..

Uses: used as a part of combination therapy to treat HIV infections.

Adverse effects:

Severe GI intolerance, abdominal pain, taste perversion,

heperglycemia, lipodystrophy syndrome.

2.1.4 Drug Profile of Lopinavir73

Description: white to light tan powder.

Category: Antiretroviral

Structure:

Fig: 2.4 Structure of Lopinavir

68

Chemical formula: C37H48N4O5

Molecular Weight: 628.80

IUPAC Name:

2H) – pyrimidineacetamide N-[[4-(2,6- methyl

phenoxy)acetyl]amino]- 3- hydroxy 5- phenyl- 1- (phenyl methyl) pentyl,

tetrahydro-α- (1- methyl ethyl)- 2- ox.

Solubility:

Freely soluble in methanol and ethanol, soluble in isopropanol and

practically insoluble in water.

Mol. mass : 628.810 g/mol

Pharmacokinetic data

Protein binding : 98-99%

Half life : 5 to 6 hours

Bioavailability : 60%

Mechanism of Action

Lopinavir, an inhibitor of the HIV-1 protease, prevents cleavage of

the Gag-Pol polyprotein, resulting in the production of immature, non-

infectious viral particles. Lopinavir is a protease inhibitor. Proteases are

enzymes essential for successful viral replication inside human cells. The

amount of Lopinavir in the blood stream stays much higher if it is taken

with a small amount of Ritonavir, another protease inhibitor. The

combination of Lopinavir and Ritonavir as Protease inhibitors prevents

the protease enzyme from working. HIV protease act like a chemical

scissors. It cuts the raw material for HIV into specific pieces needed to

build a new virus. Protease inhibitors ―gum up‖ these scissors.

69

PHARMACOKINETICS:

The pharmacokinetic properties of lopinavir co-administered with

ritonavir have been evaluated in healthy adult volunteers and in HIV-1

infected patients; no substantial differences were observed between the

two groups. Lopinavir is essentially completely metabolized by CYP3A.

Ritonavir inhibits the metabolism of lopinavir, thereby increasing

the plasma levels of lopinavir.

Absorption:

In a pharmacokinetic study in HIV-1 positive subjects (n = 19),

multiple dosing with 400/100 mg Lopinavir twice-daily with food for 3

weeks produced a mean ± SD Lopinavir peak plasma concentration

(Cmax) of 9.8 ± 3.7 μg/mL, occurring approximately 4 hours after

administration. The mean steady-state trough concentration prior to the

morning dose was 7.1 ± 2.9 μg/mL and minimum concentration within a

dosing interval was 5.5 ± 2.7 μg/mL.

Lopinavir AUC over a 12 hour dosing interval averaged 92.6 ± 36.7

μg/mL. The absolute bioavailability of lopinavir co-formulated with

ritonavir in humans has not been established. When administered

under fasting conditions, both the mean AUC and Cmax of lopinavir were

22% lower for the lopinavir oral solution relative to the capsule

formulation.

Plasma concentrations of lopinavir and ritonavir after

administration of two 200/50 mg lopinavir tablets are similar to three

133.3/33.3 mg lopinavir capsules under fed conditions with less

pharmacokinetic variability.

Distribution:

At steady state, lopinavir is approximately 98-99% bound to

plasma proteins. Lopinavir binds to both alpha-1-acid glycoprotein (AAG)

70

and albumin; however, it has a higher affinity for AAG. At steady state,

lopinavir protein binding remains constant over the range of observed

concentrations after 400/100 mg LOPINAVIR twice-daily, and is similar

between healthy volunteers and HIV-1 positive patients.

Metabolism:

In vitro experiments with human hepatic microsomes indicate that

lopinavir primarily undergoes oxidative metabolism. Lopinavir is

extensively metabolized by the hepatic cytochrome P450 system, almost

exclusively by the CYP3A isozyme.

Ritonavir is a potent CYP3A inhibitor which inhibits the

metabolism of lopinavir, and therefore increases plasma levels of

lopinavir. A 14C-lopinavir study in humans showed that 89% of the

plasma radioactivity after a single 400/100 mg lopinavir dose was due to

parent drug. At least 13 lopinavir oxidative metabolites have been

identified in man. Ritonavir has been shown to induce metabolic

enzymes, resulting in the induction of its own metabolism.

Elimination

Following a 400/100 mg14C-lopinavir/ritonavir dose,

approximately 10.4 ± 2.3% and 82.6 ± 2.5% of an administered dose of

14C-lopinavir can be accounted for in urine and feces, respectively, after

8 days.

Adverse effects:

Frequent diarrohea in 13.8% to 23.8% of patients Occasional

nausea, vomiting, abdominal pain, headache and Rashes. As a protease

inhibitor causes hyperlipidemia, hyperglycemia.

Uses: Very potent and currently among the first line treatment for HIV

infection.

71

2.1.5 Drug Profile of Valganciclovir74

Valganciclovir hydrochloride is an antiviral medication used to treat

cytomegalovirus infections. As the L-valyl ester of ganciclovir, it is

actually a prodrug for ganciclovir. After oral administration, it is rapidly

converted to ganciclovir by intestinal and hepatic esterases.

Structure:

Fig No: 2.5 Structure of Valganciclovir

Chemical IUPAC Name:

[2-[(2-amino-6-oxo-3H-purin-9-yl)methoxy]-3-hydroxypropyl]

(2S)-2- amino-3-methylbutanoate.

Molecular formula C14H22N6O5·HCl

Molecular weight 390.83.

Synonyms: Cymeval,L-valine, ester with ganciclovir ,Valganciclovir

Brand Names: Cymeval, Valcyte

Halflife: 3-4hrs

Bioavailability: 60%

Solubility: soluble in water 50mg/ml at 250c.

72

Pharmacology:

Valganciclovir is an antiviral medication used to treat

cytomegalovirus infections. As the valyl ester of ganciclovir, it is actually

a prodrug for ganciclovir. After oral administration, it is rapidly converted

to ganciclovir hepatic esterases.

Mechanism of Action:

Valganciclovir is a prodrug of ganciclovir that exists as a

mixture of two diastereomers. After administration, these diastereomers

are rapidly converted to ganciclovir by hepatic and intestinal esterases. In

cytomegalovirus (CMV)-infected cells, ganciclovir is initially

phosphorylated to the monophosphate form by viral protein kinase, then

it is further phosphorylated via cellular kinases to produce the

triphosphate form. This triphosphate form is slowly metabolized

intracellularly. The phosphorylation is dependent upon the viral kinase,

and occurs preferentially in virus-infected cells. The virustatic activity of

ganciclovir is due to the inhibition of viral DNA synthesis by ganciclovir

triphosphate.

2.2 POLYMER PROFILES

2.2.1 Polymer Profile of Gelucire 43/0175

Chemical Name: Physical Appearance: Waxy Solid Pellets

Melting Point: 43°C

Description: Gelucire® 43/01 is a carrier for oral formulations and

specifically for hard or soft gelatin dosage forms.

Applications: Gelucire® 43/01 can protect the active moiety from light,

moisture and oxidation, and can be used as an oily vehicle in Self

73

Emulsifying Lipidic Formulations (SELF type SEDDS and SMEDDS).

Inert vehicle; Carrier or protective matrix; Sustained release agent.

Gelucires are a family of vehicles derived from mixtures of mono-,di-, and

triglycerides with polyethylene glycol (PEG)esters of fatty acids. Gelucires

are available with a range of properties depending on their Hydrophilic

LipophilicBalance (HLB 1-18) and melting point (33°C-65°C) range.16,17

The Gelucires containing only PEG esters.Gelucire 43/01 is a class of

highly hydrophobic lipid with HLB 1 and melting point 43oC.Gelucire

43/01 comprises mixrure of saturated triglycerides of different fatty acids

melting at 43oC. Extreme hydrophobicity of Gelucire 43/01 is attributed

to absence of PEG esters which inturn procides release regarding ability.

2.2.2 Polymer Profile of Compritol 888 ATO76

Common name: Glyceryl behenate

Physical appearance: Atomized powder

Meltingpoint: 70°C

HLB Value: 2

Synonyms: Compritol888 ATO; 2, 3-dihydroxypropyl docosanoate;

docosanoic acid, 2,3-dihydroxypropyl ester;E471; Glycerol behenate;

glyceryl monobehenate. Tribehenin is used as a synonym for glyceryl

tribehenate.

Chemical Name:

Docosanoic acid, monoester with glycerin (glyceryl behenate)

Docosanoic acid, diester with glycerin (glyceryl dibehenate)

Docosanoic acid, trimester with glycerin (glyceryl tribehenate)

74

Functional category: Coating agent, Tablet binder, Tablet and Capsule

lubricant.

Solubility: Soluble, when heated, in chloroform and dichloromethane.

Practically insoluble in ethanol (95%), hexane, mineral oil, and water.

Applications in Pharmaceutical Formulation or technology: Glyceryl

Behenate is used in cosmetics, foods, and oral pharmaceutical

formulations. In cosmetics, it is mainly used as a viscosity-increasing

agent in emulsions;

Compritol® 888 ATO is used both as lubricant and a sustained release

agent for oral dosage forms:

Sustained release agent: used at levels of 10% to 20% (possibly higher),

for the development of tablets, it forms an inert matrix which, ‗in vivo‘,

slowly releases the active through erosion/diffusion. Used between 2% to

20% in a coating processes, such as hot melt coating (Gattecoat®

process), the coated drug molecules can be formulated with other

ingredients and then compressed in to tablets with sustained

releaseproperties.

Powerful lubricant: Used at a concentration of 1% to 3% for the

formulation of tablets and capsules, Compritol® 888 ATO is an effective

problem solver for cases of chemical incompatibility. It has binding

properties, it does not effect tablet hardness and is unaffected by

mixing/production parameters.

2.2.3 Polymer Profile of Precirol® ATO 577

Common Name: Glycerylpalmitostearate

Chemical Name: 1, 2, 3-Propanetriol hexadecanoate octadecanoate

Synonyms: Precirol; Octadecanoic acid, ester with 1,2,3-propanetriol

hexadecanoate

75

Molecular weight: 632.995 g/mol

Molecular formula: C37H76O7

Physical appearance: Atomized powder

Melting point: 56°C

HLB Value: 2

IUPAC name: hexadecanoic acid; octadecanoic acid; propane-1, 2, 3-triol

Applications: Precirol® ATO 5 a multipurpose functional excipient: a

sustained release agent, a lubricant and a taste masking agent for oral

dosage forms:

Sustained release agent: used at levels of 10% to 20% for the

development of tablets, it forms an inert matrix which, ‗in vivo‘, slowly

releases the active through erosion/diffusion. Used between 3% to 20%

in a coating processes, such as hot melt coating (Gattecoat® process), the

coated drug molecules can be formulated with other ingredients and then

compressed in to tablets with sustained release properties.

Powerful lubricant: Used at a concentation of 1% to 4% for the

formulation of tablets and capsules, It has binding properties, it does not

effect tablet hardness and is unaffected by mixing/production

parameters.

2.2.4 Polymer Profile of Lubritab®78

Common Name: Hydrogenated Vegetable Oil.

Appearance: White powder with a characteristic odor

Moisture & Coloration: Colorless or slightly yellow

Melting range: 57 - 70°C

76

Iodine value: Not more than 5

Saponification value: 175 – 200

Odor: Characteristic of fats.

Relative Density (SG): 0.9 g/ml

Solubility: Insoluble in water, Soluble in many organic solvents.

Description:

Lubritab® is made from fully hydrogenated refined vegetable oil that is

sprayed into a dry, fine powder. Lubritab® has been specifically created

for application in the production of pharmaceutical tablets.

Applications and Use:

An edible product of vegetable origin, Lubritab® is low in ash content with

practically no trace of heavy metals. The low iodine value and low acid

value indicate that Lubritab® is less chemically reactive than other

commonly used lubricants, thus assuring excellent formulation

compatibility.

While Lubritab® is generally used as a lubricant in a range of 0.5 -

4.0%, it is also employed as an auxiliary dry binder when tablets and

capsules tend to cap or laminate. In such cases, the addition of up to 5%

could eliminate these problems and aid in producing satisfactory tablets.

It is most effective when added in the dry state in the last blending

operation before compression and blended for 10 - 15 minutes. When

using Lubritab® it is recommended that an anti-adherent also be

considered.

Lubritab® can also be used in controlled release applications. In

this type of formulation, it is used at ca 20 - 40% of the formulation in

direct compression wax matrix systems, and it can be used in both melt

applications.

77

2.2.5 Polymer Profile of Cremophor ® EL79

ChemicalName: Ethoxylated castor oil.

Synonyms: Castor oil ethoxylated; Polyoxyethylene castor oil; RO 40; BY

140; PEG Castor oil

Appearance: White to slightly yellowish powder.

Chemical Nature: Nonionic solubilizer made by reacting castor oil with

ethylene oxide in a molar ratio of 1 : 35. Followed by a purification

process.

Composition: The main component of Cremophor EL is glycerol-

polyethylene glycol ricinoleate, which, together with fatty acid esters of

polyethyleneglycol, represents the hydrophobic part of the product. The

smaller, hydrophilic part consists of polyethylene glycols and ethoxylated

glycerol.

Saponification value: 65 – 70

Acid value: < 2.0

Hydroxyl value: 65 – 78

Iodine value: 25 – 35

pH (10% in water): 5.0 - 7.0

Ethylene oxide: < 1

Density (25 °C): 1.05 - 1.06 g/ml

Solubility:

Forms clear solutions in water and also dissolves in a wide range of

organic solvents, such as ethanol, n-propanol, isopropanol, ethyl acetate,

chloroform, carbon tetrachloride, trichloroethylene, toluene and xylene.

78

Applications and Use:

Used as emulsifier, penetrating agent, antifoaming agent, additive,

foaming agent, stabilizer, lubricant, solubilizing agent, levelling agent,

antistatic agent, washing agent, dispersing agent, parting agent,

degreasing agent, plasticizing agent, thickening agent, viscosity

conditioning agent and chemical intermediate in the industry.

2.2.6 Polymer Profile of Carnauba Wax80

Nonproprietary Names:

BP: Carnauba Wax

JP: Carnauba Wax

PhEur: Carnauba Wax

USP-NF: Carnauba Wax

Synonyms: Brazil wax; caranda wax; cera carnauba; E903.

Empirical Formula and Molecular Weight:

HOCH2(CH2OCH2)mCH2OH where m represents the average

number of oxyethylene groups. Alternatively, the general formula

H(OCH2CH2)nOH may be used to represent polyethylene glycol, where n

is a number. The average molecular weights of typical polyethylene

glycols. The number that follows PEG indicates the average molecular

weight of the polymer.

Fig: 2.6 Structural of Carnauba Wax

79

Functional Category:

Ointment base; plasticizer; solvent; suppository base; tablet and capsule

lubricant, coating agent.

Applications in Pharmaceutical Formulation or Technology:

Carnauba wax is widely used in cosmetics, certain foods, and

pharmaceutical formulations. Cosmetically, carnauba wax is commonly

used in lip balms.

Carnauba wax is the hardest and highest-melting of the waxes

commonly used in pharmaceutical formulations and is used primarily as

a 10% w/v aqueous emulsion to polish sugar-coated tablets.

Aqueous emulsions may be prepared by mixing carnauba wax with

an ethanolamine compound and oleic acid. The carnauba wax coating

produces tablets of good luster without rubbing.

Carnauba wax may also be used in powder form to polish

sugarcoated tablets.

Carnauba wax (10–50% w/w) is also used alone or with other

excipients such as hypromellose, hydroxypropyl cellulose, alginate/

pectin-gelatin, Eudragit, and stearyl alcohol to produce sustained release

solid-dosage formulations. Carnauba wax has been experimentally

investigated for use in producing microparticles in a novel hot air coating

(HAC) process developed as an alternative to conventional spray-

congealing techniques.

Carnauba wax consists primarily of a complex mixture of esters of

acids and hydroxy acids, mainly aliphatic esters, o-hydroxy esters, p-

methoxycinnamic aliphatic esters, and p-hydroxycinnamic aliphatic

diesters composed of several chain lengths, in which C26 and C32

alcohols are the most prevalent.

80

In addition, carnauba wax has been used to produce gel beads for

intragastric floating drug delivery and has been investigated for use in

nanoparticulate sunscreen formulations.

Description:

Carnauba wax occurs as a light brown- to pale yellow-colored

powder, flakes, or irregular lumps of a hard, brittle wax. It has a

characteristic bland odor and practically no taste. It is free from

rancidity. Various types and grades are available commercially.

Stability and Storage Conditions:

Carnauba wax is stable and should be stored in a well-closed

container, in a cool, dry place.

2.2.7 Polymer Profile of Geleol Pastilles81

Nonproprietary Names:

BP: Glyceryl Monostearate 40–55

JP: Glyceryl Monostearate

PhEur: Glycerol Monostearate 40–55

USP-NF: Glyceryl Monostearate

Appearance:

Glyceryl monostearate is a white or almost white to cream-coloured, wax-

like solid in the form of beads, flakes or powder.

Description:

Glyceryl monostearate is waxy to the touch and has a slight fatty odour

and taste.

81

Structural Formula:

Fig: 2.7 Structure of Glyceyl Monostearate

Empirical Formula and Molecular Weight: C21H42O4 358.6

Melting Point:

Glyceryl monostearate has a melting point of ≥ 55°C .

Commercial Grades:

Commercially available glyceryl monostearate contains a mixture of

variable proportions of glyceryl monostearate and glyceryl

monopalmitate.

Solubility:

Glyceryl monstearate is insoluble in water but is soluble in mineral and

fixed oils .

Functional Category:

Emollient; emulsifying agent; solubilizing agent; stabilizing agent;

sustained-release agent; tablet and capsule lubricant.

Applications in Pharmaceutical Formulation or Technology:

The many varieties of glyceryl monostearate are used as nonionic

emulsifiers, stabilizers, emollients, and plasticizers in a variety of food,

82

pharmaceutical, and cosmetic applications. It acts as an effective

stabilizer, that is, as a mutual solvent for polar and nonpolar compounds

that may form water-in-oil or oil-in-water emulsions.These properties

also make it useful as a dispersing agent for pigments in oils or solids in

fats, or as a solvent for phospholipids, such as lecithin.

Glyceryl monostearate has also been used in a novel fluidized hot-

melt granulation technique for the production of granules and tablets.

Glyceryl monostearate is a lubricant for tablet manufacturing and may be

used to form sustained-release matrices for solid dosage forms.

Sustained-release applications include the formulation of pellets for

tablets or suppositories and the preparation of a veterinary bolus.

Glyceryl monostearate has also been used as a matrix ingredient for a

biodegradable, implantable, controlledrelease dosage form.

Stability and Storage Conditions

If stored at warm temperatures, glyceryl monostearate increases in

acid value upon aging owing to the saponification of the ester with trace

amounts of water. Effective antioxidants may be added, such as

butylated hydroxytoluene and propyl gallate.

Glyceryl monostearate should be stored in a tightly closed

container in a cool, dry place, and protected from light.

Compatability:

Self-emulsifying grades of glyceryl monostearate are available and

have been reported to be incompatible with acidic substances.

2.2.8 Polymer Profile of Polyoxyethylene Stearates (Myrj-52)82

Nonproprietary Names

The polyoxyethylene stearates are a series of polyethoxylated

derivatives of stearic acid. Of the large number of different materials

commercially available, one type is listed in the USP32–NF27. JP:

Polyoxyl 40 Stearate USP-NF: Polyoxyl 40 Stearate.

83

Synonyms:

Ethoxylated fatty acid esters; macrogol stearates; Marlosol; PEG

fatty acid esters; PEG stearates; polyethylene glycol stearates; poly(oxy-

1,2-ethanediyl) a-hydro-o-hydroxyoctadecanoate; polyoxyethylene glycol

stearates. Polyoxyethylene stearates are nonionic surfactants produced

by polyethoxylation of stearic acid.

Two systems of nomenclature are used for these materials. The

number ‗8‘ in the names ‗poloxyl 8 stearate‘ or ‗polyoxyethylene 8

stearate‘ refers to the approximate polymer length in oxyethylene units.

The same material may also be designated ‗polyoxyethylene glycol 400

stearate‘ or ‗macrogol stearate 400‘ in which case, the number ‗400‘

refers to the average molecular weight of the polymer chain.

Structure:

Fig: 2.8 Structure of Polyoxyethylene Stearates (MYRJ-52)

Structural Formula

Structure A applies to the monostearate; where the average value

of n is 6 for polyoxyl 6 stearate, 8 for polyoxyl 8 stearate, and so on.

Structure B applies to the distearate; where the average value of n

is 12 for polyoxyl 12 distearate, 32 for polyoxyl 32 distearate, and so on.

Functional Category:

Emulsifying agent; solubilizing agent; wetting agent.

84

Applications in Pharmaceutical Formulation or Technology:

Polyoxyethylene stearates are generally used as emulsifiers in oil-

inwater- type creams and lotions. Their hydrophilicity or lipophilicity

depends on the number of ethylene oxide units present: the larger the

number, the greater the hydrophilic properties. Polyoxyl 40 stearate has

been used as an emulsifying agent in intravenous infusions.

Polyoxyethylene stearates are particularly useful as emulsifying

agents when astringent salts or other strong electrolytes are present.

They can also be blended with other surfactants to obtain any

hydrophilic–lipophilic balance for lotions or ointment formulations.

Description:

Polyoxyl 40 stearate Waxy solid, with a faint, bland, fat-like odor,

off-white to light tan in color

Stability and Storage Conditions:

Polyoxyethylene stearates are generally stable in the presence of

electrolytes and weak acids or bases. Strong acids and bases can cause

gradual hydrolysis and saponification. The bulk material should be

stored in a well-closed container, in a dry place, at room temperature.

2.2.9 Polymer Profile of Sedefos 83

Sedefos is a mixture of: Triceteareth-4 phosphate, Ethylene glycol

palmitostearate and Diethylene glycol palmitostearate

Common Name: Glycerylpalmitostearate

Molecular weight: 632.995 g/mol

85

Molecular formula: C37H76O7

Physical appearance and odour : Semi-solid and faint

Solubility:

Insoluble in Ethanol

Slightly soluble in Chloroform, Methylene chloride.

Dispersible in Water, Soluble at 60°C in mineral oils

Melting point: 56°C

Storage recommendations:

Product should be re-analyzed after a 3-year storage period under

recommended storage conditions.

During storage at high temperature (> 35°C), there is a risk of pellet

agglomeration.

Store at a temperature inferior or equal to 30 °C.

Store the product in its original packaging sealed tightly, protected from

light and moisture.

Applications:

O/W emulsifier -It enables the emulsion of the non-aqueous

phase (ex: glycerin).

Aninonic self emulsifying base for oil in water emulsion.

2.2.10 Polymer Profile of Carbowax 84

Polyethylene Glycols (PEGs) are a family of water-soluble linear

polymers formed by the addition reaction of ethylene oxide. The

generalized formula for polyethylene glycol is:

H-(OCH2CH2)n-OH

where "n" is the average number of repeating oxyethylene groups.

86

Each CARBOWAX PEG is designated by a number that represents

its average molecular weight. For example, CARBOWAX PEG 600

consists of a distribution of polymers of varying molecular weights with

an average of 600, which corresponds to an approximate average number

of repeating oxyethylene groups ("n") of 13.The letter "E" indicates Europe

grade.

Carbowax Polyethylene Glycols are available in average molecular weights

ranging from 200 to 8000.

2.2.11 Polymer Profile of Polymethacrylates 85

Nonproprietary Names: BP:

Ammonio Methacrylate Copolymer (Type A)

Ammonio Methacrylate Copolymer (Type B)

Basic Butylated Methacrylate Copolymer

Methacrylic Acid–Ethyl Acrylate Copolymer (1 : 1)

Methacrylic Acid–Ethyl Acrylate Copolymer (1 : 1)

Dispersion 30 per cent:

Methacrylic Acid–Methyl Methacrylate Copolymer (1 : 1)

Methacrylic Acid–Methyl Methacrylate Copolymer (1 : 2)

Polyacrylate Dispersion (30 per cent)

PhEur: Ammonio Methacrylate Copolymer (Type A)

Ammonio Methacrylate Copolymer (Type B)

Basic Butylated Methacrylate Copolymer

Methacrylic Acid–Ethyl Acrylate Copolymer (1: 1)

Methacrylic Acid–Ethyl Acrylate Copolymer (1: 1)

USP-NF: Amino Methacrylate Copolymer

Ammonio Methacrylate Copolymer

Ammonio Methacrylate Copolymer Dispersion

87

Ethyl Acrylate and Methyl Methacrylate Copolymer

Dispersion

Methacrylic Acid Copolymer

Methacrylic Acid Copolymer Dispersion

Synonyms:

Acryl-EZE; acidi methacrylici et ethylis acrylatis polymerisatum;

acidi methacrylici et methylis methacrylatis polymerisatum; ammonio

methacrylatis copolymerum; copolymerum methacrylatis

butylatibasicum; Eastacryl; Eudragit; Kollicoat MAE;

polyacrylatisdispersion 30 per centum; polymeric methacrylates.

Chemical Name and Trade Name:

Table 2.1 Chemical Name and CAS Registry Number of Polymethacrylates

CHEMICAL NAME TRADE NAME

Poly(butyl methacrylate, (2-dimethylaminoethyl)

methacrylate, methyl methacrylate) 1 : 2 : 1

Eudragit E PO

Poly(methacrylic acid, methyl methacrylate) 1 : 1

Eudragit L 100

Poly(methacrylic acid, methyl methacrylate) 1 : 2

Eudragit S 100

Poly(ethylacrylate,methylmethacrylate,trimethylammoni

oethyl methacrylate chloride) 1 : 2 : 0.2

Eudragit RL 100

Poly(ethyl acrylate, methyl methacrylate,

trimethylammonioethyl methacrylate chloride)

1 : 2 : 0.1

Eudragit RS 100

Empirical Formula and Molecular Weight

The Ph Eur 6.2 describes methacrylic acid–ethyl acrylate

copolymer(1 : 1) as a copolymer of methacrylic acid and ethyl acrylate

88

having a mean relative molecular mass of about 250 000. The ratio of

carboxylic groups to ester groups is about 1 : 1. It may contain suitable

surfactants such as sodium dodecyl sulfate or polysorbate80. An

aqueous 30% w/v dispersion of this material is also defined in a separate

monograph. Methacrylic acid–methyl methacrylate copolymer (1 : 1) is

described in the PhEur 6.0 as a copolymer of methacrylic acid and

methyl methacrylate having a mean relative molecular mass of about 135

000. The Ph Eur 6.0 describes basic butylated methyacrylate

copolymeras a copolymer of (2dimethylaminoethyl) methacrylate, butyl

methyacrylate, and methyl methacrylate having a mean relative

molecular mass of about 150 000.

Structural formula

Fig No 2.9: Structure of Polymethacrylate

For Eudragit E:

R1, R3 = CH3,R2 = CH2CH2N(CH3)2,R4 = CH3, C4H9

For Eudragit L and Eudragit S:

R1, R3 = CH3,R2 = H,R4 = CH3

For Eudragit FS:

R1 = H,R2 = H, CH3,R3 = CH3,R4 = CH3

For Eudragit RL and Eudragit RS:

R1 = H, CH3,R2 = CH3, C2H5, R3 = CH3

89

Functional Category:

Film-forming agent; tablet binder; tablet diluent.

Density:

Table 2.2 Densities of Various Polymethacrylates

TYPE DENSITY g/cm3

Eudragit EPO 0.811–0.821 g/cm3

Eudragit L100 0.831–0.852 g/cm3

Eudragit S100 0.831–0.852 g/cm3

Eudragit RL 0.816–0.836 g/cm3

Eudragit RS 0.816–0.836 g/cm3

Description:

Eudragit E PO is a whitefree-flowing powder with at least 95% of

dry polymer.

Eudragit L and S, also referred to as methacrylic acidcopolymers in

the USP32–NF27 monograph, are anionic copolymerization products of

methacrylic acid and methyl methacrylate. The ratio of free carboxyl

groups to the ester is approximately 1 : 1 in

Eudragit L (Type A) and approximately 1 : 2 in Eudragit S (Type B).

Both polymers are readily soluble in neutral to weakly alkalineconditions

(pH 6–7) and form salts with alkalis, thus affording film coats that are

resistant to gastric media but soluble in intestinalfluid.

Eudragit RL and Eudragit RS, also referred to as ammonio

methacrylate copolymers in the USP32–NF27 monograph, arecopolymers

synthesized from acrylic acid and methacrylic acidesters, with Eudragit

RL (Type A) having 10% of functional quaternary ammonium groups and

Eudragit RS (Type B) having5% of functional quaternary ammonium

90

groups. The ammoniumgroups are present as salts and give rise to pH-

independent permeability of the polymers. Both polymers are water-

insoluble,and films prepared from Eudragit RL are freely permeable to

water, whereas, films prepared from Eudragit RS are only slightly

permeable to water. They are available as 12.5% ready-to-usesolutions in

propan-2-ol–acetone (60 : 40). Solutions are colorlessor slightly yellow in

color, and may be clear or slightly turbid; they have an odor

characteristic of the solvents. Solvent-free granules(Eudragit RL 100 and

Eudragit RS 100) contain 597% of thedried weight content of the

polymer.

Eudragit L 100-55 (prepared by spray-drying Eudragit L 30 D-55)

is a white, free-flowing powder that is redispersible in water to form a

latex that has properties similar to those of Eudragit L 30 D.

Applications in Pharmaceutical Formulation or Technology

Polymethacrylates are primarily used in oral capsule and tablet

formulations as film-coating agents. Depending on the type of polymer

used, films of different solubility characteristics can be produced.

Eudragit EPO is used as a plain or insulating film former. It is

soluble in gastric fluid below pH 5

Eudragit S and FS are soluble at pH > 7. The S grade is generally

used for coating tablets

Eudragit RL, RS, are used toform water-insoluble film coats for

sustained-release products.

Polymethacrylates are also used as binders in both aqueous and

organic wet-granulation processes. Larger quantities (5–20%) of dry

polymer are used to control the release of an active substance from a

91

tablet matrix. Solid polymers may be used in direct compression

processes in quantities of 10–50%.Polymethacrylate polymers may

additionally be used to form the matrix layers of transdermal delivery

systems and have also been used to prepare novel gel formulations for

rectal administration.

Stability and Storage Conditions

Dry powder polymer forms are stable at temperatures less than

308C. Above this temperature, powders tend to form clumps, although

this does not affect the quality of the substance and the clumps can be

readily broken up. Dry powders are stable for at least 3 years if stored in

a tightly closed container at less than 308C.Dispersions are sensitive to

extreme temperatures and phase separation occurs below 08C.

Dispersions should therefore be stored at temperatures between 5 and

258C .

2.2.12 Polymer Profile of Hydroxy Propyl Methyl Cellulose

(Methocel) 86

Chemical name: Cellulose, 2- hydroxypropyl methyl ether

Fig No: 2.10 Structure of Hydroxy Propyl Methyl Cellulose

92

Where R is H, CH3 or [CH

3CH (OH)CH

2]

Non- proprietary name:

1. BP : Hypromellose

2. USP : Hydroxypropyl methylcellulose

Synonym:

Methylhydroxy propylcellulose; hydroxypropyl methylether, Benecel

MHPC; Metolose; Pharmacoat, Methocel, Tylopur.

Molecular weight: 10000-1500000

Description:

Hydroxypropyl methylcellulose is an odorless and tasteless, white

or creamy –white colored fibrous powder.

Melting point:

Browns at 190-200ºC, chars at 225-230ºC, glass transition

temperature is 170-180ºC.

Solubility:

Soluble in cold water, forming a viscous colloidal solution,

practically insoluble in chloroform, ethanol (95%) and ether, but soluble

in mixtures of ethanol and dichloromethane and mixtures of methanol

and dichloromethane. Certain grades of HPMC are soluble in aqueous

acetone solutions, mixtures of dichloromethane and propane-2-ol and

other organic solvents.

Application in pharmaceutical formulation or Technology:

Hypromellose is widely used in oral and topical pharmaceutical

formulations.

93

a) In oral products, hypromellose is primarily used as a tablet binder, in

film coating and as an extended release tablet matrix.

b) Depending upon the viscosity grade, concentration of 2-20% w/w are

used for film-forming solutions to film coat tablets. Lower-viscosity

grades are used in aqueous film-coating solutions, while higher-

viscosity grades are used with organic solvents.

c) Hypromellose at concentration between 0.45-1.0% w/w may be added

as a thickening agent to vehicles for eye drops and artificial tear

solution.

d) Also, used as an emulsifier, suspending agent, and stabilizing agent in

topical gels and ointments.

e) In addition, hypromellose is used in the manufacture of capsules, as

an adhesive in plastic bandages and as a wetting agent for hard

contact lenses. It is also widely used in cosmetics and food products.

Storage condition: It should be stored in a well-closed container, in a

cool, dry place.

2.2.12.1 Polymer Profile of HPMC K4M87

Chemical Name: Cellulose hydroxypropylmethylether

Structural Formula:

Fig No: 2.11 Structure of HPMC K4M

Empirical Formula: (OCH2CH (OH) CH3) n

94

Molecular Weight: 10,000-1500000.

Nonproprietary Names:

BP: Hypromellose

JP: Hydroxypropylmethylcellulose

PhEur: Hypromellosum

USPNF: Hypromellose

Synonyms:

Benecel MHPC; E464; Hydroxypropylmethylcellulose; HPMC;

Methocel;Methyl cellulose propylene glycol ether;

Methyl hydroxypropylcellulose

2.2.12.2 HPMC K15M 88

Description:

White to slightly off white,fibrous or granular powder.

Solubility:

Soluble in chloroform,ethanol, ether, but soluble in water +alcohol,

ethanol,methanol+dichloromethane .

PH - 5to8.

Methoxyl content 19.0 to 24.0%.

Hydroxyl propyl content: 7.0 to 12.o%.

Apparent viscocity: 75000-140000mpa.s by rotation.

75000-140000cP by ubbelohde.

95

Pharmaceutical applications:

1) It can be used in controlled release hydrophilic matrix system as

granulation binder,and as viscocity modifier and suspending

agent in liquid medium (2-5%)

2) 2-20% are used for film forming solution to film coat tablets.

3) controlled release grades are especially selected particle size materials

for increased consistency in matrix formulation(10-80%).

4) A hydrophilic matrix controlled release system composed of polymer

wetting, hydration and dissolution.

2.2.13 Polymer Profile of Polyethylene Glycol 89

Nonproprietary Names: BP: Macrogols

JP: Macrogol 400

Macrogol 1500

Macrogol 4000

Macrogol 6000

Macrogol 20000

PhEur: Macrogols

USP-NF: Polyethylene Glycol

Synonyms:

Carbowax; Carbowax Sentry; Lipoxol; Lutrol E; macrogola; PEG;

Pluriol E; polyoxyethylene glycol.

Chemical Name : a-Hydro-o-hydroxypoly(oxy-1,2-ethanediyl)

96

Empirical Formula :

HOCH2(CH2OCH2)mCH2OH

where m represents the average number of oxyethylene groups.

Alternatively, the general formula H(OCH2CH2)nOH may be used to

represent polyethylene glycol, where n is a number m in the previous

formula.

Functional Category

Ointment base; plasticizer; solvent; suppository base; tablet and

capsule lubricant.

Applications in Pharmaceutical Formulation or Technology

Polyethylene glycols (PEGs) are widely used in a variety of

pharmaceutical formulations, including parenteral, topical, ophthalmic,

oral, and rectal preparations. Polyethylene glycol has been used

experimentally in biodegradable polymeric matrices used in controlled-

release systems.

Polyethylene glycols are stable, hydrophilic substances that are

essentially nonirritant to the skin; They do not readily penetrate the skin,

although the polyethylene glycols are water-soluble and are easily

removed from the skin by washing, making them useful as ointment

bases.

Solid grades are generally employed in topical ointments, with the

consistency of the base being adjusted by the addition of liquid grades of

polyethylene glycol. Mixtures of polyethylene glycols can be used as

suppository bases.

Stability and Storage Conditions

97

Polyethylene glycols are chemically stable in air and in solution,

although grades with a molecular weight less than 2000 are hygroscopic.

Polyethylene glycols do not support microbial growth,and they do not

become rancid. Polyethylene glycols and aqueous polyethylene glycol

solutionscan be sterilized by autoclaving, filtration, or gamma irradiation.

2.2.13.1 POLYETHYLENE GLYCOLS-600090

Average Molecular Weight. 7000 - 9000

pH of 5 % aq. Solution: 4 - 7

Freezing Point: 56 - 63 0 C

Viscosity at 100o C 470 - 900 CST.

Description:

PEG - 6000 is a high molecular weight polymer of ethylene oxide

and is a blend of polymers with different degrees of polymerisation .

Like all other PEGs , PEG-6000 is readily soluble in water . So

water can be the most economical solvent for this , apart from other

organic solvents .

PEG-6000 acts as binder & dry lubricant due to its laminar

structure and therefore can be used in the manufacture of pills and

tablets for certain pharmacutical preparations

Other Applications:

Other applications of PEG-6000 include as wetting agents to

inhibit soap cracking , as binder for facial makeup , as antidusting agent

for after bath talcum powder , lubricant in paper industry , as a tyre

mounting agent , as an additive in grease , as plasticiser in synthetic

resin.

PEG-6000 dissolved in lower glycols in place of paraffin wax are

used for enbalming of histological and other medical specimens.

98

Compatibility :

Compatibility of glycols is proved to be good in formulations of

Nitrofurazone , Undecanoic acid , Sulphur , Hydrocortisone , Methyl

Salicylate , Benzyl Benzoate etc.

Incompatibility :

Glycols are not compatible with Penicillin , Bicitracine , Iodine ,

Potassium Iodide , Sorbitol , Tannic Acid , Bismuth salts. Glycols are also

not suitable with Polyethylene , Backlite & celluloids.

Storage : Under dry conditions and at room temperature in sealed

containers.

2.2.14 Polymer Profile of Carbopol 93491

Non proprietary names: Carbomers(BP), carbomera(PhEur),

carbomer(USPNF).

Synonyms: Acritamer, acrylic acidpolymer, carbopol, carboxy

polymethykene, polyacrylic acid, carboxyvinyl polymer.

Chemical name: Carbomer.

Structural Formula:

Fig No- 2.12: Structure of Carbopol 934

99

Functional category:

Bioadhesive, emulsifying agent, release modifying agent,

suspending agent, tablet binder, viscosity increasing agent.

Description:

Carbomers are white coloured, fluffy, acidic, hygroscopic powders

with a slight characteristic odour.

Density(bulk): 1.76-2.08g/cm3.

Glass transition temperature: 100-1500C.s

Solubility:

Soluble in water and, after neutralization, in ethanol(95%) and

glycerine.

Stability and storage:

Carbomers are stable, hygroscopic materials that may reduces its

stability when exposed to excessive temperatures. Carbomer powder

should be stored in an airtight, corrosive resistant container in a cool,

dry place.

Incompatabilities:

Carbomers are discoloured by resorcinol and are incompatable

with phenol, cationic polymers, strong acids, and high levels of

electrolytes.

100

Applications in Pharmaceutical Formulation or Technology

Carbomers are used in liquid or semisolid pharmaceutical

formulations as rheology modifiers. Formulations include creams, gels,

lotions and ointments for use in ophthalmic rectalt opical and

vaginalpreparations.

In tablet formulations, carbomers are used as controlled release

agents and/or as binders. Carbomer polymers have also been

investigated in the preparation of sustained-release matrix beads as

enzyme inhibitors of intestinal proteases in peptide-containing dosage

forms as a bioadhesive for a cervical patch and for intranasally

administered microspheres in magnetic granules for site-specific drug

delivery to the oesophagus and in oral mucoadhesive controlled

drugdelivery systems.

Carbomers copolymers are also employed as emulsifying agents in

the preparation of oil-in-water emulsionsfor external administration.

Carbomer 934 has been investigated as a viscosity-increasing aid in the

preparation of multiple emulsion microspheres Carbomers are also used

in cosmetics. Therapeutically,carbomer formulations have proved

efficacious in improving symptoms of moderate-to-severe dry eye

syndrome.

Table 2.3: Functional Uses of Carbomers

USE CONCENTRATION (%)

Emulsifying agent 0.1–0.5

Gelling agent 0.5–2.0

Suspending agent 0.5–1.0

Tablet binder 0.75–3.0

Controlled-release agent 5.0–30.0

101

Stability and Storage Conditions:

Carbomers are stable, hygroscopic materials that may be heated

at temperatures below 1040C for up to 2 hours without affecting their

thickening efficiency. However, exposure to excessive temperaturescan

result in discoloration and reduced stability.

2.2.15 Polymer Profile of Sodium Alginate92

Description:

Sodium alginate occurs as a white or buff colored powder which is

odorless and tasteless. The powder may be course or fine.

Solubility:

Slowly soluble in water, forming a viscous, colloidal solution.

Insoluble in alcohol and hydro-alcoholic solutions in which alcohol

content is greater than 30%by weight. It is insoluble in other organic

solvents and in acids where the PH of the resulting solution falls below

3.0

Synonym:

Sodium polymannuronate; SatialgineS 20; Album S 160 and S

15/600; Kelgin, Kelkosol, Keltone, Kelco-gel LV,HV; Sodium Alginate.

Structural formula:

Fig No- 2.13: Structure of Sodium Alginate

102

Non proprietary name: NF: Sodium alginate

BP: Sodium alginate

Empirical formula: (C6H7O6Na)n

Functional category:

NF: Suspending agent or viscosity increasing agent

Others: Disintegrating agent; tablet binder

Applications in Pharmaceutical Formulations:

1. Used in pastes and creams in concentration of 5-10%.

2. Used as stabilizer in emulsions at 1-3% concentration.

3. Used as suspending agent in between 1-5%.

4. Used as tablet disinegrant in between 2.5-10%.

5. Used as tablet binder in between 1-3%.

Stability and Storage Conditions:

Since sodium alginate is hygroscopic, the moisture content at

equilibrium is a function of the relative humidity. Dry storage stability is

excellent when the powder is stored in a well closed container at

temperatures of 25c or less. Solutions are more stable at PH between 4

and 10. Above PH 10 solution viscosity decreases. Solution should not be

stored in metal containers.

2.2.16 Polymer Profile of Magnesium Stearate93

Description:

Magnesium stearate is a fine, white, precipitated or milled, Impalpable powder of

low bulk density, having a faint odor or and a characteristic taste. The powder is

greasy to the touch and readily adheres to the skin.

Nonproprietary names:

BP: Magnesium Stearate

103

JP: Magnesium Stearate

Ph Eur: Magnesii stearas

USPNF: Magnesium Stearate

Synonyms:

Magnesium octadecananoate; Octadecanoic acid; Magnesium salt.

Chemical name: Octadecanoic acid magnesium salt

Empirical formula: C36H70MgO4

Molecular weight: 591.34

Structural formula:

(H3C-(CH2)16-CO2)2Mg

Functional category: Tablet and capsule lubricant.

Melting point:

117-150 °c (commercial samples)

126-130 °c (high purity Magnesium stearate )

Solubility:

Practically insoluble in ethanol, ethanol (95%), ether and water, slightly

soluble in warm benzene and warm ethanol (95%).

Stability and storage conditions:

Magnesium stearate is stable and should be stored in a well-closed

container.

Applications in Pharmaceutical Technology:

1) Magnesium stearate is widely used in cosmetics, foods, and

pharmaceutical formulations.

104

2) It is primarily used as a lubricant in capsule and tablet manufacture

at concentrations between 0.25 and 5%w/w.

3) Magnesium stearate is also used in Barrier creams.

2.2.20 Polymer Profile of Micro Crystalline Cellulose (Avicel 102)94

Description: White, odourless, tasteless,crystalline powder.

Synonym Avicel Ph, Cellulose, Emsocel

Structural formula:

Fig No-2.14: Structure of Avicel

Molecular formula: C6H10O5)n.

Molecular weight: 36000 DALTONS.

pH; 5.0-7.0

Sulphated ash : <0.1%

Water soluble substance: <0.05%

Heavy metals: <10PPM

Loss on drying: <7.0%

105

Melting point: 260-270oC

Particle size: <8.0 RETAINED ON 60 MESH

Fuctional category:

Adsorbent; suspending agent; tablet and capsule diluent; tablet

disintegrant.

Table: 2.4 Functional Uses of Micro crystalline Cellulose

USE CONCENTRATION

Adsorbent 20-90%

Anti adherent 5-20%

Capsule binder/diluents 20-90%

Tablent disintegrant 5-15%

Tablet binder/diluents 20-90%

Application in pharmaceutical formulation:

1) It is widely used in pharmaceuticals as binder, diluent in oral

tablets and capsules, where it used in wet granulation and direct

compression process.

2) It has some lubricant and disintegrating agent.

3) It can also be used in cosmetics and food products.

Storage:

It is stable through hygroscopic material; the material should be

closed in well closed container.