Chapter 4 Drug and Excipient Profile

4.0 DRUG AND EXCIPlENT PROFILE

4.1 DOMPERIDONE1-16

Category Peripheral dopamine receptor antagonist; antiemetic.

Molecular Weight 425.911 g/mol
Molecular Formula C22H24 ClN5O2
Melting Point 242.5 0C
pKa 7.9
5-chloro-1-(1-[3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-
IUPAC Name
yl)propyl] piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one
Structure O
NH
O N
HN
Cl
N N

Description Domperidone is a benzimidazole derivatives and a member of

dopamine receptor antagonist.
Dose Adult - 20 40 mg t.d.s ; Children - 0.3 mg / kg t.d.s.
Solubility Very slightly soluble in water and alcohol, slightly soluble in
methanol.

Pharmacology Domperidone acts as a gastrointestinal emptying adjunct and

peristaltic stimulant. The antiemetic properties are related to
dopamine receptor blocking activity at both chemoreceptor trigger
zone and gastric level. It shows affinity for the D2 and D3 dopamine
receptors.
Pharmacokinetics Absorbed from the GIT, undergoes first pass metabolism in liver.
Bioavailability is 5% following oral administration. Metabolites are
excreted in faeces and in the urine. Plasma half-life is 7 - 8 hours.
Onset of action is within 1 hour of administration.
Routes of Administration Oral, intravenous, rectal
Indications As an anti-emetic for relief on nausea and vomiting of any cause.
Radiation, uremia. Reflux oesophagitis.

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Drug Interactions This medication enhances movement in the digestive tract, it may
affect the absorption and action of other medications. Opioid
analgesics and antimuscarinics antagonize its effects.

4.2 GLICLAZIDE1,2,17-23

Category Hypoglycemic Agents, Sulfonylureas, Antidiabetic

Molecular Weight 323.412 g/mol
Molecular Formula C15H21N3O3S
Melting Range 180 0C 182 0C
pKa 14.13
N-(hexahydrocyclopenta[c]pyrrol-2(1H)-ylcarbamoyl)-4-
IUPAC Name
methylbenzene sulfonamide
Structure
O OO
S N
N N
H H
H3C

Description Gliclazide belongs to category of sulfonylurea compounds drugs.

Gliclazide is a type of second generation sulfonylurea.
Dose Adult - 20 40 mg t.d.s ; Children - 0.3 mg / kg t.d.s.
Solubility Very slightly soluble in water and alcohol, sparingly soluble in
dimethylformamide, slightly soluble in methanol.

Pharmacology Gliclazide is a second generation sulphonylurea which acts as a

hypoglycemic agent. It stimulates cells of the islet of Langerhans
in the pancreas to release insulin. It also enhances peripheral
insulin sensitivity. Overall, it potentiates insulin release and
improves insulin dynamics.
Pharmacokinetics Rapidly and well absorbed but may have wide inter- and intra-
individual variability. Peak plasma concentrations occur within 4-6
hours of oral administration. 94%, highly bound to plasma

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proteins. Extensively metabolized in the liver. Less than 1% of the

orally administered dose appears unchanged in the urine.
Routes of Administration Oral
Indications For the treatment of NIDDM in conjunction with diet and exercise
Drug Interactions Hyperglycemic action may be caused by chlorpromazine,
glucocorticoids, and progestogens. Its hypoglycemic action may be
potentiated by alcohol.

4.3 POLYETHYLENE GLYCOL24-28

Synonym Carbowax; Carbowax Sentry; Lipoxol; Lutrol E; PEG; Pluriol

E; polyoxyethylene glycol.
Chemical Name -Hydro--hydroxypoly(oxy-1,2-ethanediyl
Molecular Formula HOCH2(CH2OCH2)mCH2OH where m represents the average
number of oxyethylene groups.
Category Ointment base; plasticizer; solvent; suppository base; tablet and
capsule lubricant. Used to enhance the aqueous solubility or
dissolution characteristics of poorly soluble compounds by
making solid dispersions with an appropriate polyethylene
glycol.

Structural Formula

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Description Solid grades (PEG>1000) are white or off-white in color, and

range in consistency from pastes to waxy flakes. They have a
faint, sweet odor. Grades of PEG 6000 and above are available
as free-flowing milled powders. Liquid grades (PEG 200600)
occur as clear, colorless or slightly yellow-colored, viscous
liquids. They have a slight but characteristic odor and a bitter,
slightly burning taste. PEG 600 can occur as a solid at ambient
temperatures.

Properties PEG 4000 PEG 6000 PEG 8000

Appearance (25) White flakes White flakes White flakes
pH value(1 %water Solution 5.0~7.0 5.0~7.0 5.0~7.0
Moisture % 1.0 1.0 1.0
Viscosity (mm2/s) 6.0~9.0 11.0~16.0 16.0~20.0
Average molecular weight 3500~4500 5500~7500 750~8800
g/mol

4.4 POLYVINYL PYRROLIDONE24,29

Synonym Polyvinyl pyrrolidone; Povidone; PVP

Chemical Name 1-Ethenyl-2 pyrrolidone homopolymer
Molecular Formula (C6H9NO)n
Category Disintegrant, dissolution enhancer, suspending agent, tablet binder.
Structural Formula

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Description Povidone occurs as a fine, white to creamy white colored, odorless,

hygroscopic powder. Povidone with K-values equal to or lower than
30 are manufactured by spray drying and occur as spheres. Povidone
K 90 and higher K-values Povidone are manufactured by drum drying
and occur as plates.USP describes Povidone as a synthetic polymer
consisting of linear 1-vinyl-2-pyrrolidone groups, the differing degree
of polymerization of which results in polymers of a various molecular
weights. It is characterized by the viscosity.
Molecular Weight K- value Approximate Molecular Weight
12 2500
15 8000
17 10000
25 30000
30 50000
60 400000
90 1000000
120 3000000
Properties Povidone K 30 Povidone K 90
Clarity (10% in water) Clear Clear
Nitrogen content (%) 12.0-12.8 12.0-12.8
Water (Karl Fischer %) 5.0 5.0
pH value (5% in water) 3.0-5.0 4.0-7.0
Applications Povidone is used as solubilizer in oral and parenteral formulations,
and to enhance the dissolution of poorly soluble drugs from solid
dosage forms. The solubility of poorly soluble active drugs may be
increased by mixing with the Povidone.

4.5 SODIUM STARCH GLYCOLATE24,30,31

Synonym Carboxymethyl starch, sodium salt; caboxymethylamylum

natricum, Explosol, Explotab, Glycolys, Primojel
Chemical Name Sodium carboxymtehyl starch
Molecular Weight 500000-11000000

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Category Tablet and capsule disintegrant

Structural Formula

Description Sodium starch glycolate is a white or almost white free flowing

very hygroscopic powder. Under microscope it is seen to consist
of granules, irregularly shaped, ovoid or pear shaped, 30-100m
in size. Very fine, white or off white, free flowing powder;
odorless or almost odorless.
Properties IP USP 26-NF21
pH 5.5 - 7.5 5.5 - 7.5
Loss on Drying, NMT % 10 10
Iron, NMT % 0.002 0.002
Heavy Metals, NMT % 0.002 0.002
Sodium Chloride, NMT % 10 7
Applications Sodium starch glycolate is widely used in oral pharmaceuticals as
a disintegrant in capsule and tablet formulations. It is commonly
used in tablets.

4.6 KYRON28, 31,32

Kyron is derived from the polymer cross-linked polyacrylic used in the pharmaceutical
industry to mask the taste of bitter medicine to achieve stability and drugs. It is white to off white
fine powder, swellable in water. KYRON T 314 is derived from cross linked polymer
of polycarboxylic acid as per USP/NF and has a K+ ionic form. It is a very high purity
polymer used in pharmaceutical formulation as a super fast disintegrant as well as
dissolution improver in solid dosage form like tablet, capsule, pellets etc. It is suitable for the
both wet granulation as well as direct compression system for tablet formulations. Different
grades of Kyron with specifications showed in table 4.1.

Table 4.1: Different grades of Kyron with specifications.

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KYRON GRADES
Specification T-104 T-114 T-134 T-154 T-159 T-123
Pharmacopoeia In house In house Polacrilin Sodium In house In house
potassium polystyrene
USP Sulphonate
USP
Type Weak acid Weak acid Weak acid Strong acid Strong acid Weak base
Functionality -COO- -COO- -COO- -SO-3 -SO-3 Secondary
amine
Ionic Form Hydrogen Hydrogen Potassium Sodium Hydrogen Free base
Matrix Polyacrylic Polyacrylic Polyacrylic Polystyrene Polystyrene Polystyrene
copolymer copolymer copolymer copolymer copolymer copolymer
Moisture content <10 <5 <10 <10 <10 <10
(%)
Appearance White to off White to off White to off off White to off White to White to off
white free white free white free golden golden white free
flowing flowing flowing yellow free yellow free flowing
powder powder powder flowing flowing powder
powder powder

4.7 MANNITOL 1,24,27,28,33,34,35

Synonym Cordycepic acid, Emprove, manna sugar, D-mannite, peralitol.

Chemical Name D-mannitol
Molecular Formula C6H14O6
Molecular Weight 182.17
Category Diluent, plasticizer, sweetening agent, tablet and capsule diluent,
therapeutic agent, tonicity agent.
Structure

Description It is a hexahydric alcohol related to mannose and is isomeric with alcohol.

It occurs as a white, odorless, crystalline powder, or free flowing granules.
It has a sweet taste, approximately as sweet as glucose and half as sweet as
sucrose and imparts a cooling sensation in mouth.
Applications It is widely used as diluent in tablet formulations. It is not hygroscopic
hence can be used with moisture sensitive active ingredients. It may be

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used with direct compression with the wet granulation.

Solubility 1 in 5.5 in water,1 in 18 in glycerine and 1 in 83 in ethanol at 20C

4.8 ASPARTAME 1,24,27,28,36,37,38

Synonym Aspartamum, aspartyl phenylalanine methyl ester.

Chemical Name N-L--aspartyl-L-phenylalanine-1-methyl ester
Molecular Formula C14H18N2O5
Molecular Weight 294.30
Category Sweetening agent
Structure

Description It is an off white, almost odorless crystalline powder with an

intensely sweet taste.
Applications It enhances flavor systems and can be used to mask some unpleasant
taste characteristics. Approximate sweetening power is 180-200
times that of sucrose.
Solubility Slightly soluble in ethanol (95%), sparingly soluble in water. At 20C
the solubility is 1% w/v at the isoelectric point pH 5.2.Solubility
increases at higher temperature and in acidic pH.

4.9 TALC 1,24,27,28

Synonym Hydrous magnesium calcium silicate, , magnesium hydrogen metasilicate, ,

purified French chalk, soapstone, steatite, talcum.
Chemical Name Talc
Formula Mg6(Si2O5)4(OH)4
Category Anticaking agent, glidants, tablet and capsule diluent, tablet and capsule
lubricant.

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Description It is very fine, white, odorless, impalpable, unctuous, crystalline powder. It

adheres to skin and is soft to touch and free of grittiness.
Applications Used in oral solid dosage forms as lubricant and diluent. Talc is used as
lubricant in tablet formulations.
Solubility Practically insoluble in dilute acids and alkalis, organic solvents and water.

4.10 AVICEL 24,27,28

Synonym Avicel PH, cellulose gel, hellulosum microcrystallinum, crystalline

cellulose,E460,Emocel
Chemical Name Cellulose
Formula (C6H10O5)n~36000 where n~220
Category Adsorbent, suspending agent, tablet and capsule diluent, tablet
disintegrant.
Structural Formula

Description It is a purified, practically depolymerised cellulose that occurs as a

white, odorless, tasteless, crystalline powder composed of porous
particles.

Applications It is used as binder and diluent in tablet formulations. It can be used

with the wet granulation and direct compression. it also has
disintegrant properties that make it useful in tabletting
Solubility Slightly soluble in 5% sodium hydroxide solution, practically
insoluble in water, dilute acids and most organic solvents.

4.11 MAGNESIUM STEARATE 1,24,27,28,39,40

Synonym Dibasic magnesium stearate, magnesium distearate, magnesium

octadeconate, octadecanoic acid magnesium salt.
Chemical Name Ocatdecanoic acidmagnesium salt

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Molecular Formula C36H70MgO4

Molecular Weight 591.24
Category Tablet and capsule lubricant
Structure

Description It is a very fine, light white, precipitated or milled, low bulk density,
having a faint odor of stearic acid and a characteristic taste.
Applications It is used as lubricant in tablet and capsule manufacture in
concentration of 0.25% and 5.0%w/w.
Solubility Practically insoluble in ethanol, ether, slightly soluble in warm
benzene and warm ethanol (95%), sparingly soluble in water.

4.12 CROSSCARMELLOSE SODIUM 1,24,27

Synonym Ac-di-sol, carmellose natricum conexum, cfrosslinked

carboxymethylcellulose sodium, explocel, modified cellulose gum,
Nymcel, Primellose.
Chemical Name Cellulose, carboxymethyl ether, sodium salt, crosslinked.
Category Tablet and capsule disintegrant
Structural Formula

Description It occurs as white, odorless, tasteless, granular powder. It is

hygroscopic after drying.

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Applications It is used in oral formulations as disintegrant for capsules, tablets and

granules. It can be used with both direct compression and wet
granulation.
Solubility Insoluble in water, although crosscarmellose swells 4-8 times its
original volume on contact with water. Practically insoluble in
acetone, ethanol and toluene.

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