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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.
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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
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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.
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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
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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.
Recommended