chapter 2 drug and excipients profile -...

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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.

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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.


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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.


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

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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).

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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.

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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.


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.


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.



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

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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.


S CH3

CH3

O


Applications : Used as permeation enhancer to improve transdermal

delivery. It has also been used in the parenteral

preparations and in paint formulations.


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.


CH3

OH

O


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


Description : Clear, colourless, practically odourless liquid.

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CH3

O

CH3

OCH3


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


Description : A yellowish to pale brown, oily liquid with a

characteristic lard-like odour and taste.


H3C(CH

2)6

(CH2)6COOH


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

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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).

chapter 2 drug and excipients profile -...

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