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CHAPTER 2
DRUG AND EXCIPIENTS PROFILE
2.1 SALBUTAMOL SULPHATE
Structural formula:
CHCH2NHC(CH
3)3
OH
HOCH2
OH
2
H2SO
4
Synonym : Albuterol sulphate
Molecular weight : 288.35
Molecular formula : C13H21NO3, H2SO4
Description : Odourless, slightly bitter in taste, white or almost
white powder.
Standards : Salbutamol sulphate IP (1985) contains not less
than 98% and not more than 101% of C13H21NO3,
H2SO4 calculated with reference to the dried
substance.
Solubility : Soluble in four parts of water and slightly soluble in
ethanol 96% of chloroform and ether.
Storage : Should be protected from light
Melting point : 150 ºC
Category : Salbutamol sulphate is a short-acting 2-adrenergic
receptor agonist.
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Pharmacology : Salbutamol exerts a relatively selective action on
the 2-adrenergic receptors of the bronchial and vascular smooth muscles. It is
administered either by inhalation or orally for the symptomatic relief of
bronchospasm associated with chronic or acute asthma, bronchitis or other
obstructive pulmonary diseases.
Uses: It is used in the treatment of asthma, chronic bronchitis,
emphysema and other bronchopulmonary disorders involving bronchospasm.
The drug is also used to arrest premature labour and in ocular hypertension. It
is effective when applied topically but it often causes severe hyperaemia. In
congestive heart disease, it is used for low output states. The drug improves
cardiac output by reducing left ventricular after load but has little effect on
ventricular filling pressure.
Dose: Salbutamol is used as the base in aerosol inhalers and as the
sulphate salt in other dosage forms. A dose equivalent to 2 - 4 mg of
Salbutamol, 3 or 4 times per day is prescribed for adults, while for children
of 2 - 6 years, a dose of 1 - 2 mg, 3 or 4 times and 2 mg for older children is
prescribed.
Salbutamol is administered as an aerosol inhalation in doses of up
to 200 micrograms 3 or 4 times a day. The usual dose for children is on
inhalation of 100 micrograms 2 - 4 times daily. Salbutamol sulphate is used as
a respiratory solution containing the equivalent of 0.5% salbutamol.
A solution for injection containing the equivalent of 50 or 500
micrograms or one milligram of salbutamol per millilitre is used in
bronchospasm. The usual dose by subcutaneous or intramuscular injection is
equivalent of 8 g of salbutamol / Kg body weight every 4 h and slow
intravenous injection, 4 g / Kg body weight, repeated as necessary (Walter
Lund 1994; Martindale 1999; Hardmans et al 2001).
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2.2 HYDROXYPROPYL METHYLCELLULOSE
Description: Odourless, tasteless, white or creamy-white coloured fibrous or
granular powder.
Molecular weight: Approximately 10,000 - 1,500,000.
Structural formula:
Applications : Primarily in the oral products hydroxypropyl
methylcellulose was used as a tablet binder, extended
release tablet matrix, suspending and thickening agent
particularly in ophthalmic preparations. It is widely
used in cosmetics and food products and also used as
a wetting agent for hard contact lenses and as an
adhesive in plastic bandages.
Acidity / Alkalinity : pH = 5.5 - 8.0 for a 1% w/w aqueous solution.
Density (tapped) : 0.50 - 0.70 g / cm3 for pharmacoat.
Melting point : Browns at 190-200 oC. Glass Transition Temperature
is 170 - 180 oC.
Solubility : Soluble in cold water and practically insoluble in
ethanol (95%), ether and chloroform. But soluble in
mixtures of methanol and dichloromethane and
mixtures of ethanol and dichloromethane.
Stability : Its powder is a stable material although it is
hygroscopic after drying.
29
Incompatibilities : Incompatible with some oxidizing agents and will not
complex with metallic salts and ionic organics.
Safety : Extensively used in cosmetics, food products and
widely used as an excipient in oral and topical
formulations (Amley and Weller 1994).
2.3 POLYVINYL ALCOHOL
Chemical Name : Ethanol homopolymer
Structural formula:
Emperical formula : (C2H4O) n
Description : Odourless and white to cream coloured granular powder.
Molecular weight : 30,000 - 20,000
Applications : Particularly used in ophthalmic products and also
used in the preparation of cosmetics, transdermal
patches, sustained release tablet formulations and in
various jellies as a viscosity increasing agent.
Melting point : 228 oC for fully hydrolyzed grades, 180 - 190
oC for
partially hydrolyzed grades.
Refractive index : nD25
= 1.49 - 1.53
Solubility : Soluble in hot or cold water. Slightly soluble in some
polyhydroxy compounds, certain amines and amides.
Practically insoluble in ketones, oils, esters, aliphatic,
aromatic and chlorinated hydrocarbons.
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Specific gravity : 1.19 - 13.1 for solid at 25 oC, 1.03 for 10% w / v
aqueous solution at 25 oC.
Viscosity (dynamic) : 21 - 33 (Dynamic viscosity of 4% w / v aqueous
solution at 25 oC (mPas).
Stability : Undergoes slow degradation at 100 oC and rapid
degradation at 200 oC and on exposure to light it is
stable.
Incompatibilities : At high concentration, incompatible with most
inorganic salts especially sulphates and phosphates.
Safety : Generally regarded as a nontoxic material. It is non-
irritant to the skin and eyes up to 10% and upto 7%
may be used in cosmetics (Rowe et al 2006).
2.4 CARBOPOL
Chemical name : Carboxy polymethelene
Empirical formula : (C3H4O2) x (-C3H5-sucrose) y
Grades : 907, 910, 934, 934P, 940, 941, 971P, 974P, 980 and 981.
Structural formula :
Description : White, fluffy, acidic, hygroscopic powder with a
slight characteristic odour.
Molecular weight : 1 x 106 to 4 x 106.
Density : Bulk: 5 g / cm3. Tapped: 1.4 g / cm
3.
Viscosity : 29,400 to 39,400 cps at 2 oC (0.5% neutralized
aqueous solution).
pH : 2.5 - 3.0 (1% aqueous solution).
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Solubility : Soluble in water, alcohol and glycerin.
Stability : It is relatively unaffected by temperature variations,
not subjected to hydrolysis or oxidation and is
resistant to bacterial growth.
Applications : It is excellent thickening, emulsifying, suspending
and gelling agent. It is used as a tablet binder in
sustained release formulations affording zero- to near
zero order release. It is used as the bioadhesive
component in mucoadhesive ointments, gels and
tablets.
Safety : No primary irritation or any evidence of allergic
reactions has been observed in human beings
following topical application.
Incompatibility : It is observed with cationic polymers, phenols,
resorcinol and high concentration of electrolytes
(Rowe et al 2006).
2.5 SODIUM CARBOXYMETHYLCELLULOSE
Chemical name : Carboxymethyl ether, sodium salt, cellulose.
Molecular Weight : 90,000 - 70,0000.
Description : Almost white coloured, granular and odourless.
Structural formula :
32
Applications : Widely used as a viscosity modifier, tablet binder,
disintegrant, stabilizing agent and suspending agent
for powders either for topical application or
parenteral and oral administration. It is also used in
food products and cosmetics.
Density (bulk) : 0.75 g / cm3
Dissociation constant: pKa = 4.30
Melting point : Browns at approximately 227 oC, chars at
approximately 252 oC.
Viscosity : The viscosity of aqueous 1% w/v solutions is 5 - 4000
mPas
Stability : It is stable though hygroscopic material. Solutions
exhibit maximum viscosity and stability at pH 7-9.
Aqueous solutions are stable between pH 2-10,
precipitation can occur at pH below 2 and viscosity
rapidly decreases at pH above 10.
Incompatibilities : Observed with xanthan gum, strong acidic solutions
and soluble salts of iron and other metals.
Safety : Regarded as a nontoxic and non-irritant material in
cosmetics and food products. Its oral consumption in
large amounts can cause a laxative effect and also
irritant to eyes (Rowe et al 2006).
2.6 POLYVINYL PYRROLIDONE
Chemical name : 2-Pyrrolidone,1-ethenyl-homopolymer,1-vinyl-2-
pyrrolidone polymer.
Empirical formula : (C6H9NO) n
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Description : A white to creamy white, odourless, hygroscopic
powder.
Molecular weight : 10,000
Structural formula:
Density : 1.17-1.18 g / mL
Bulk volume : 2.3 mL / g
Tapped volume : 1.9 mL / g
Solubility/ miscibility: Upto 60% it is readily soluble in water. Freely soluble
in many organic solvents. Insoluble in ethers,
hydrocarbons, carbon tetra chloride, ethyl acetate and
mineral oil.
Softning point : 1500 oC
Stability : It is stable in short cycles of heat exposure around
110 - 1300 oC. Steam sterilization of an aqueous
solution does not alter its properties.
Applications : Used as a carrier for drugs, dispersing agent,
suspending or viscosity builder, tablet binder, diluents
and coating agent.
Incompatibilities : Found to be compatible in solution and with large
range of inorganic salts, natural and synthetic resins
and other chemicals.
Safety : Chemically inert and non-toxic. It has no irritant
effect on skin and causes no sensitization. It does not
irritate the mucus membrane of rabbit eye (Rowe et al
2006).
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2.7 CHITOSAN
Chemical name : Poly-b-(1,4)-2-Amino-2-deoxy-D-glucose
Description : Odourless, white or creamy-white powder or flakes.
Structural formula :
Molecular formula : C6H11NO4n
Molecular weight : 10,000 - 1,000,000
Solubility : Easily in water.
Moisture content : 10%
Ash content : 2.0%
Applications : Excellent film forming agent, additives, cosmetics
and good bacterial inhibitor. Also used for the
preservation of fruits and vegetables. It is widely
applied for improving immunity, activating cells,
preventing cancer, decreasing blood fat and blood
pressure, adjusting blood sugar, fighting against
ageing and adjusting organism environment.
Incompatibilities : Incompatible with strong oxidizing agents.
Stability : Chitosan powder is a stable material at room
temperature, although it is hygroscopic after drying.
Safety : Widely for use as an excipient in oral, cosmetics and
other pharmaceutical formulations. Generally regarded
as a nontoxic and nonirritant material. It is
biocompatible with both healthy and infected skin
and shown to be biodegradable (Goosen 1996; Rowe
et al 2006).
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2.8 EUDRAGIT - L100
Molecular weight : Is approximately 135,000.
Description : White powders with a faint characteristic odour.
Solubility : Dissolves in methanol, ethanol, aqueous isopropyl
alcohol and acetone. Practically insoluble in ethyl
acetate, methylene chloride, petroleum ether and
water.
Particle size : At least 95%, less than 0.25 mm.
Film formation : When poured onto a glass plate, a clear film forms
upon evaporation of the solvent.
Applications : 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 RL, RS and NE 30D are used to form water
insoluble film coats for sustained release products.
Eudragit RL films are more permeable than those of
Eudragit RS and by mixing the two types together
films of varying permeability can be obtained.
Eudragit RS-100 (RS) and RL-100 (RL) are
copolymers of acrylic and methacrylic acid esters that
contain a low level of quaternary ammonium groups.
RS has a lower content of charged groups, thus
displaying less water permeability and swellability in
comparison with RL (Eudragit technical sheets).
Eudragit acrylic resins exhibit a broad spectrum of
physicochemical properties and are used in a variety
of pharmaceutical applications, such as film coating
36
of oral formulations and preparation of controlled-
release drug systems.
Stability : Minimum stability dates are given on the product
labels and batch-related certificates of analysis.
Storage : Protect from warm temperatures and against moisture.
Safety : Polymethacrylate co-polymers are widely used as
film coating materials in oral pharmaceutical
formulations. They are also used to a lesser extent in
topical formulations and are generally regard as non-
toxic and non-irritant materials (Goto et al 1986;
Amley and Weller 1994).
2.9 POLYETHYLENE GLYCOL-400
Chemical name : -Hydro- -hydroxypoly-(oxy-1,2-
ethanediyl),polyethylene glycol.
Empirical formula : HOCH2 (CH2OCH2) n CH2OH
Description : Odour is slight but characteristic, clear, viscous
liquids colourless or slightly yellowish.
Molecular weight : 380 - 420
Structural formula:
H
O
OH
n
Density : 1.11-1.14 g / cm3
Refractive index : 1.465
Solubility/miscibility : Soluble in water, alcohols, glycols, acetone, glycerol,
and benzene. Miscible in all proportions with other
polyethylene glycols (PEGs).
37
Surface tension : 44 mN / m
Stability : Chemically stable in air and in solution. Oxidation
may occur if PEGs are exposed for long periods to
temperatures exceeding 500 oC. PEGs do not support
microbial growth or become rancid.
Applications : Used as a gelling agent, suppository base, suspending
agent, solvent, binder, solubilizer, plasticizer for film
coating, lubricant etc.
Incompatibilities : Incompatible with carbonic acid, aspirin, mercury,
silver salts, bismuth, iodine, potassium iodide and
theophylline derivatives.
Safety : Toxicity and skin irritation is low. It is permitted as
an additive to feeds and drinking water. The
maximum recommended concentration of PEG-300
in parenteral solution is 30% (Rowe et al 2006).
2.10 PROPYLENE GLYCOL
Chemical name : 1, 2-Propanediol -1, 2- Propanediol -1, 2-Propanediol
Empirical Formula : C3H8O2
Molecular Weight : 76.09
Description : It is a clear, colourless, viscous, practically odourless
liquid with a sweet and slightly acrid taste resembling
that of glycerine.
38
Structural Formula :
C
H
H
C
H
OH
CH
H
H
OH
Boiling point : 188 °C
Density : 1.038 g / cm3 at 20 °C
Melting point : -59 °C
Solubility : Miscible with acetone, chloroform, ethanol (95%),
glycerine and water, soluble at 1 in 6 parts of ether,
not miscible with light mineral oil or fixed oils, but
will dissolve in some essential oils.
Stability : Stable in a well-closed container at cool temperature.
It is chemically stable when mixed with ethanol
(95%), glycerine, or aqueous solutions.
Applications : In parenteral and nonparenteral pharmaceutical
formulations, widely used as a solvent, extractant and
preservative. Commonly used as a plasticizer and as a
carrier for emulsifiers.
Incompatibilities : Incompatible with potassium permanganate.
Safety : Regarded as a relatively nontoxic material and
minimally irritant in topical preparations. It is also
used in foods and cosmetics. Pain or irritation may
cause due to parenteral administration when it is used
in high concentration (Rowe et al 2006).
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2.11 MENTHOL
Chemical name : 5-Methyl-2-(1-methylethyl)cyclohexanol.
Empirical formula : C10H20O
Description : It is colourless, prismatic or acicular shiny crystals or
hexagonal or fused masses with a strong
characteristic odour and taste.
Molecular weight : 156.27
Structural formula : CH
3
OH
CHCH
3 CH3
Applications : Used as a flavouring agent or odours enhancer in
pharmaceuticals and toiletry products. Also
investigated as a skin permeation enhancer.
Boiling point : 212 °C
Melting point : 34 °C
Solubility : Very soluble in ethanol (95%), chloroform, ether,
fatty oils and liquid paraffin, soluble in acetone and
benzene, very slightly soluble in glycerine, practically
insoluble in water.
Stability : It should be stored in a well-closed container at a
temperature not exceeding 25 °C.
Incompatibilities : Incompatible with butylchloral hydrate, camphor,
chloral hydrate, chromium trioxide, -naphthol,
phenol, potassium permanganate, pyrogallol,
resorcinol and thymol.
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Safety : Essentially non-irritant and following topical
application may produce hypersensitivity. Inhalation
of large quantities can result in serious adverse
reactions (Rowe et al 2006).
2.12 SACCHARIN SODIUM
Chemical name : 1, 2-Benzisothiazol-3(2H)-1,1-dioxidesodium salt.
Empirical formula : C7H4NNaO3S
Description : White, odourless or faintly aromatic, efflorescent,
crystalline powder and has an intensely sweet taste.
Molecular weight : 205.16
Structural formula :
S
N
O
O O
Na+
Applications : It is an intense sweetening agent used in beverages,
food products, table-top sweeteners, tablets, powders,
medicated confectionery, gels, suspensions, liquids,
mouthwashes and in vitamin preparations also.
Injection of saccharin sodium has been used to
measure the arm to tongue circulation time.
Density (bulk) : 0.8 - 1.1 g/cm3 (76% saccharin sodium), 0.86 g/cm
3
(84% saccharin sodium).
Melting point : Decomposes upon heating.
Solubility : In buffer solutions, pH 2.2 (phthalate), pH 4.0
(citrate-phosphate), pH 7.0 (citrate-phosphate), pH
41
9.0 (borate), ethanol (95%), propylene glycol, and
water.
Stability : Significant decomposition occurs only when it is
exposed to a high temperature (125 °C) at a low pH 2
for over 1 h. The 84% grade is the most stable form
of saccharin sodium since the 76% form will dry
further under ambient conditions.
Safety : Concerned as a safe and intense sweetener (Rowe et
al 2006).
2.13 DIMETHYL SULFOXIDE
Chemical name : Sulfinylbismethane
Empirical formula : C2H6OS
Description : Colourless, hygroscopic, bitter taste, odourless, or has
a slight odour characteristic.
Structural formula :
S CH3
CH3
O
Molecular weight : 78.13
Applications : Used as permeation enhancer to improve transdermal
delivery. It has also been used in the parenteral
preparations and in paint formulations.
Boiling point : 189 °C
Dissociation constant: pKa = 31.3
Flash point (open cup): 95 °C
Specific heat : 0.7cal / g (liquid)
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Solubility : Insoluble in acetone, chloroform, ethanol (95%) and
ether. Miscible with water, ethanol (95%), ether and
most all organic solvents, immiscible with paraffins
and hydrocarbons.
Stability : Stable to heat, but temperatures between 40-60 °C a
partial breakdown may occur.
Incompatibilities : It can react with oxidizing materials.
Safety : Low systemic toxicity but causes local toxic effects.
Acts as irritant on skin, cause increases in intraocular
pressure and enhances the skin permeation.
Administration by any route is followed by a garlic-
like odour on the breath (Rowe et al 2006).
2.14 LINOLEIC ACID
Chemical name : (Z, Z)-9, 12-Octadecadienoic acid.
Empirical formula : C18H32O2
Description : Colourless to light yellow coloured oil.
Structural formula :
CH3
OH
O
Molecular weight : 280.45
Applications : As an absorption enhancer it is used in oral
formulations and in topical transdermal formulations.
But act as emulsifying agent in topical cosmetic
formulations and also as a dietary supplement in
parenteral emulsions.
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Boiling point : 230 °C at 16 mmHg
Density : 0.9007 g / cm3
Melting point : -5 °C
Refractive index : n20
D = 1.4699
Iodine value : 181.1
Solubility : Soluble in ethanol (95%), freely soluble in ether,
miscible with dimethyl formamide, fat solvents, and
oils.
Stability : It is sensitive to light, air, moisture, and heat. It
should be stored in a tightly sealed container under an
inert atmosphere and refrigerated.
Incompatibilities : Incompatible with strong oxidizing agents, reducing
agents and bases.
Safety : Generally regarded as a nontoxic material and widely
used in cosmetics and topical pharmaceutical
formulations. It can cause mild irritation on exposure
to the eyes, skin and mucous membranes (Rowe et al
2006).
2.15 ISOPROPYL MYRISTATE
Chemical name : 1-Methylethyl tetradecanoate
Empirical formula : C17H34O2
Description : Clear, colourless, practically odourless liquid.
44
Structural formula :
CH3
O
CH3
OCH3
Molecular weight : 270.5
Applications : Uses in topical pharmaceutical, cosmetic and as a
permeation enhancer for transdermal formulations.
This also been used in microspheres, component of
semisolid bases and as a solvent and as emollient.
Boiling point : 140.2 °C at 266 Pa (2 mmHg)
Flash point : 153.5 °C (closed cup)
Freezing point : 5 °C
Solubility : Soluble in acetone, chloroform, ethanol (95%), ethyl
acetate, fats, fatty alcohols, fixed oils, liquid
hydrocarbons, toluene and waxes. Practically
insoluble in glycerine, glycols and water.
Viscosity (dynamic): 5 - 7 mPas (5 - 7cP) at 25 °C
Stability : Resistant to oxidation and hydrolysis and does not
become rancid.
Incompatibilities : Incompatible with hard paraffin and also with strong
oxidizing agents.
Safety : Widely used in cosmetics and topical pharmaceutical
formulations and is generally regarded as a non-toxic
and non-irritant material (Rowe et al 2006).
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2.16 OLEIC ACID
Chemical name : (Z)-9-Octadecenoic acid
Empirical formula : C18H34O2
Description : A yellowish to pale brown, oily liquid with a
characteristic lard-like odour and taste.
Structural formula :
H3C(CH
2)6
(CH2)6COOH
Molecular weight : 282.47
Applications : Used as an emulsifying agent in foods and topical
pharmaceutical formulations and as a permeation
enhancer in transdermal formulations to improve the
bioavailability of poorly water-soluble drugs.
Density : 0.895 g / cm3
Melting point : 4 °C
Refractive index : n26
D = 1.4585
Solubility : Miscible with benzene, chloroform, ethanol (95%),
ether, hexane and fixed volatile oils and practically
insoluble in water.
Viscosity (dynamic): 26 mPas (26cP) at 25 °C
46
Stability : On exposure to air, gradually absorbs oxygen,
darkens in colour and develops a more pronounced
odour. It decomposes when heated at 80 - 100 °C.
Incompatibilities : Incompatible with aluminum, calcium, heavy metals,
iodine solutions, perchloric acid and oxidizing agents.
Safety : Ingestion of a large quantity of oleic acid can cause
rupture of red blood cells (hemolysis) and it is a
moderate skin irritant and should not be used in eye
preparations (Rowe et al 2006).