Carriers Profile AMLODIPINE - Copy

CARRIER PROFILE

66Carriers ProfileCarriers Profile

6.1 Lactose, Monohydrate

1. Nonproprietary Names

BP: Lactose

PhEur: Lactose Monohydrate

JP: Lactose Hydrate

USP-NF: Lactose Monohydrate

2. Synonyms

CapsuLac; GranuLac; Lactochem; lactosum monohydricum;

Monohydrate; Pharmatose; PrismaLac; SacheLac; SorboLac;

SpheroLac; SuperTab 30GR; Tablettose.

3. Chemical Name O-β -D-Galactopyranosyl-(1→4)-α-D-glucopyranose monohydrate.

4. Empirical Formula C12H22O11.H2O

Molecular Weight 360.31

5. Structural Formula

BBDNITM, LUCKNOW Page 28

CARRIER PROFILE

6. Functional Category

Dry powder inhaler carrier; lyophilization aid; tablet binder; tablet

and capsule diluent; tablet and capsule filler.

7. Applications in Pharmaceutical Formulation or Technology

Lactose is widely used as a filler and diluent in tablets and capsules, and to a more limited

extent in lyophilized products and infant formulas.(1–9) Lactose is also used as a diluent

in dry-powder inhalation; seeLactose, Inhalation. Various lactose grades are commercially

available that have different physical properties such as particle size distribution and flow

characteristics. This permits the selection of the most suitable material for a particular

application; for example, the particle size range selected for capsules is often dependent on

the type of encapsulating machine used.

L

Lactose, Monohydrate

Usually, fine grades of lactose are used in the preparation of tablets by the wet-granulation

method or when milling during processing is carried out, since the fine size allows better

mixing with other formulation ingredients and utilizes the binder more efficiently.

Other applications of lactose include use in lyophilized products, where lactose is added to

freeze-dried solutions to increase plug size and aid cohesion. Lactose is also used in

combination with sucrose (approximately 1 : 3) to prepare sugar-coating solutions. It may

also be used in intravenous injections.

Lactose is also used in the manufacture of dry powder formulations for use as aqueous

film-coating solutions or suspensions. Direct-compression grades of lactose monohydrate

are available as granulated/agglomerated a-lactose monohydrate, containing small

BBDNITM, LUCKNOW 9

CARRIER PROFILE

amounts of anhydrous lactose. Direct-compression grades are often used to carry lower

quantities of drug and this permits tablets to be made without granulation.

Other directly compressible lactose are spray-dried lactose and anhydrous lactose.

8. Description

In the solid state, lactose appears as various isomeric forms, depending on the

crystallization and drying conditions, i.e. α lactose monohydrate, β-lactose anhydrous, and

α-lactose anhydrous. The stable crystalline forms of lactose are α-lactose monohydrate, β-

lactose anhydrous, and stable α-lactose anhydrous. Lactose occurs as white to off-white

crystalline particles or powder. Lactose is odorless and slightly sweet-tasting; α-lactose is

approximately 20% as sweet as sucrose, while β-lactose is 40% as sweet.

9. Typical Properties

Table 6.2

Properties of Hypromellose

Properties Range

pH 5.5 -6.5

Ash 1.5 - 3.0 %

Bulk density 0.75 g/cm3

Tapped density 0.88 g/cm3

True density 1.545 g/cm3

Melting point 219 oC

Specific gravity 1.525

10. Solubility

Soluble in water and practically insoluble in chloroform, ether and ethanol.

6.2 Cellulose Microcrystalline43


BBDNITM, LUCKNOW 0

CARRIER PROFILE

BP: Microcrystalline cellulose

JP: Microcrystalline cellulose

PhEur: Cellulosum microcristallinum

USPNF: Microcrystalline cellulose

2. Synonyms

Avicel PH, Celex, cellulose gel, Celphere, Ceolus KG, crystalline cellulose, E460,

Emcocel, Ethispheres, Fibrocel, Pharmacel, Tabulose, Vivapur.

3. Chemical Name Cellulose

4. Empirical Formula (C6H10O5)n where n = 220 Molecular Weight 36000



Adsorbent, suspending agent, tablet and capsule diluent, tablet disintegrant.


Microcrystalline cellulose is widely used in pharmaceuticals, primarily as a binder/diluent

in oral tablet and capsule formulations where it is used in both wet-granulation and direct-

compression processes. In addition to its use as a binder/diluent, microcrystalline cellulose

also has some lubricant and disintegrant properties that make it useful in tableting.

Table 6.3Uses of Microcrystalline Cellulose


http://www.medicinescomplete.com/mc/excipients/current/1000296081.htm








CARRIER PROFILE

Use Concentration (% w/w)

Adsorbent 20-90

Antiadherent 5-20

Capsule binder/diluent 20-90

Tablet disintegrant 5-15

Tablet binder/diluent 20-90

8. Description

Microcrystalline cellulose is a purified, partially depolymerized cellulose that occurs as a

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

commercially available in different particle sizes and moisture grades that have different

properties and applications.

9. Solubility

Slightly soluble in 5 % w/v sodium hydroxide solution, practically insoluble in water,

dilute acids, and most organic solvents.


Table 6.4Grade Nominal mean

particle size (μm)Paricle size analysis Moisture

content (%)Mesh size Amount retained

(%)

Avicel PH -101 50 60≤ 1.0 ≤ 5.0

Properties of Microcrystalline Cellulose


CARRIER PROFILE

6.3 Povidone43


BP: Povidone

JP: Povidone

PhEur: Povidonum

USP: Povidone

2. Synonyms

E1201, Kollidon, Plasdone, poly[1-(2-oxo-1-pyrrolidinyl)ethylene], polyvidone,

polyvinylpyrrolidone, PVP, 1-vinyl-2-pyrrolidinone polymer.

3. Chemical Name 1-Ethenyl-2-pyrrolidinone homopolymer.

4. Empirical Formula (C6H9NO)n Molecular Weight 2500-3000000

PVP K-30 50000



Properties Range

pH 5.0 -7.5

Angle of repose 49 o

Bulk density 0.32 g/cm3


True density 1.512-1.668 g/cm3

Melting point 260 - 270 oc

Specific surface area 1.06-1.12 m2/g for Avicel PH-101

http://www.medicinescomplete.com/mc/excipients/current/d1e298961.htm

http://www.medicinescomplete.com/mc/excipients/current/d1e298951.htm

CARRIER PROFILE


Disintegrant, dissolution aid, suspending agent, tablet binder.


Although povidone is used in a variety of pharmaceutical formulations, it is primarily used

in solid-dosage forms. In tableting, povidone solutions are used as binders in wet-

granulation processes. Povidone is also added to powder blends in the dry form and

granulated in situ by the addition of water, alcohol, or hydroalcoholic solutions. Povidone

is used as a solubilizer in oral and parenteral formulations and has been shown to enhance

dissolution of poorly soluble drugs from solid-dosage forms. Povidone solutions may also

be used as coating agents.

Povidone is additionally used as a suspending, stabilizing, or viscosity-

increasing agent in a number of topical and oral suspensions and solutions. The solubility

of a number of poorly soluble active drugs may be increased by mixing with povidone.

Table 6.5Uses of Povidone

Use Concentration (%)

Carrier for drugs 10-25

Dispersing agent Up to 5

Eye drops 2-10


CARRIER PROFILE

Suspending agent Up to 5

Tablet binder, tablet diluent, or coating agent 0.5-5

8. Description

Povidone occurs as a fine, white to creamy-white colored, odorless or almost odorless,

hygroscopic powder.

9.Solubility

Freely soluble in acids, chloroform, ethanol , ketones, methanol, and water; practically

insoluble in ether, hydrocarbons, and mineral oil.


Table 6.6Properties of Povidone

6.4 Colloidal Silicon Dioxide43


BP: Colloidal anhydrous silica

PhEur: Silica colloidalis anhydrica

USPNF: Colloidal silicon dioxide

2. Synonyms


Properties Range

pH 3.0 - 7.0

Bulk density 0.29-0.39 g/cm3

Tapped density 0.39-0.54 g/cm3

True density 1.180 g/cm3

Melting point 150oC

CARRIER PROFILE

Aerosil, Cab-O-Sil, Cab-O-Sil M-5P, colloidal silica, fumed silica, light anhydrous silicic

acid, silicic anhydride, silicon dioxide fumed, Wacker HDK.

3. Chemical Name Silica

4. Empirical Formula SiO2 Molecular Weight 60.08

5. Structural Formula SiO2


Adsorbent, anticaking agent, emulsion stabilizer, glidant, suspending agent, tablet

disintegrant, thermal stabilizer, viscosity-increasing agent.


Colloidal silicon dioxide is widely used in pharmaceuticals, cosmetics, and food products.

Its small particle size and large specific surface area shows desirable flow characteristics

that are exploited to improve the flow properties of dry powders in a number of processes

such as tableting

Table 6.8Uses of Colloidal silicon dioxide

Use Concentration (%)

Aerosols 0.5-2.0

Emulsion stabilizer 1.0-5.0






CARRIER PROFILE

Glidant 0.1-0.5

Suspending and thickening agent2.0-10.0

8. Description

Colloidal silicon dioxide is a submicroscopic fumed silica with a particle size of about

15 nm. It is a light, loose, bluish-white-colored, odorless, tasteless, nongritty amorphous

powder.

9. Solubility

Practically insoluble in organic solvents, water, and acids, except hydrofluoric acid,

soluble in hot solutions of alkali hydroxide. Forms a colloidal dispersion with water.


Table 6.9

Properties of Colloidal silicon dioxide

Properties Range

pH 3.5-4.4

Bulk density 0.029-0.042 g/cm3


Specific surface area 200 ± 25 m2/g

6.5 Magnesium Stearate


CARRIER PROFILE


BP: Magnesium Stearate

JP: Magnesium Stearate

PhEur: Magnesium Stearate

USP-NF: Magnesium Stearate

2. Synonyms

Dibasic magnesium stearate; magnesium distearate; magnesia stearas; magnesium

octadecanoate; octadecanoic acid, magnesium salt; stearic acid, magnesium salt; Synpro

90.

3. Chemical Name Octadecanoic acid magnesium salt.

4. Empirical Formula C36H70MgO4


Tablet and capsule lubricant.


Magnesium stearate is widely used in cosmetics, foods, and pharmaceutical formulations.

It is primarily used as a lubricant in capsule and tablet manufacture at concentrations

between 0.25% and 5.0% w/w. It is also used in barrier creams.

7. Description

Magnesium stearate is a very fine, light white, precipitated or milled, impalpable powder

of low bulk density, having a faint odor of stearic acid and a characteristic taste. The

powder is greasy to the touch and readily adheres to the skin.

8.Solubility

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

benzene and warm ethanol (95%).



CARRIER PROFILE

Table 6.10

Properties of Talc

Properties Range

Bulk Density 0.159 g/cm3

Tapped Density 0.286 g/cm3

True Density 1.092 g/cm3

Melting Point 117–150°C

6.6 Sodium Starch Glycolate1.Nonproprietary Names

BP: Sodium Starch Glycolate

PhEur: Sodium Starch Glycolate

USP-NF: Sodium Starch Glycolate

2 Synonyms

Carboxymethyl starch, sodium salt; carboxymethylamylum natricum; Explosol;

Explotab; Glycolys; Primojel; starch carboxymethyl ether, sodium salt; Tablo; Vivastar P.

3 Chemical Name

Sodium carboxymethyl starch.

4. Empirical Formula

The USP32–NF27 describes two types of sodium starch glycolate, Type A and Type B,

and states that sodium starch glycolate is the sodium salt of a carboxymethyl ether of

starch or of a crosslinked carboxymethyl ether of starch.

The PhEur 6.0 describes three types of material: Type A and Type B are described as the

sodium salt of a crosslinked partly Ocarboxymethylated potato starch. Type C is described

as the sodium salt of a partly O-carboxymethylated starch, crosslinked by physical


CARRIER PROFILE

dehydration. Types A, B, and C are differentiated by their pH, sodium, and sodium

chloride content. The PhEur and USP–NF monographs have been harmonized for Type A

and Type B variants.

5. Molecular Weight

The molecular weight is typically 5 x105–1x106 .

6. Structural Formula :

7. Functional Category:

Tablet and capsule disintegrant.

8 Appilication in pharmaceutical Formulation or Technology

Sodium starch glycolate is widely used in oral pharmaceuticals as a disintegrant in

capsule and tablet formulations. It is commonly used in tablets prepared by either direct-

compression or wet-granulation processes. The usual concentration employed in a

formulation is between 2% and 8%, with the optimum concentration about 4%, although

in many cases 2% is sufficient. Disintegration occurs by rapid uptake of water followed by

rapid and enormous swelling. Although the effectiveness of many disintegrants is affected

by the presence of hydrophobic excipients such as lubricants, the disintegrant efficiency of

sodium starch glycolate is unimpaired. Increasing the tablet compression pressure also

appears to have no effect on disintegration time.

Sodium starch glycolate has also been investigated for use as a suspending vehicle.

9.Description

Sodium starch glycolate is a white or almost white free-flowing very hygroscopic powder.

The PhEur 6.0 states that when examined under a microscope it is seen to consist of:

granules, irregularly shaped, ovoid or pear-shaped, 30–100 mm in size, or rounded, 10–35

mm in size; compound granules consisting of 2–4 components occur occasionally; the


CARRIER PROFILE

granules have an eccentric hilum and clearly visible concentric striations. Between crossed

nicol prisms, the granules show a distinct black cross intersecting at the hilum; small

crystals are visible at the surface of the granules. The granules show considerable swelling

in contact with water.

10 Typical Properties

Table 6.10

Properties of Talc

Properties Range

Bulk Density 0.75 g/cm3

Tapped Density 0.90 g/cm3

True Density 1.90 g/cm3

Melting Point Chars at 200°C

Solubility

Practically insoluble in methylene chloride. It gives a translucent suspension in water.

6.6 Polyoxyethylene Sorbitan Fatty Acid Esters1.Nonproprietary Names

BP: Polysorbate 80

PhEur: Polysorbate 80

USP-NF: Polysorbate 80

2 Synonyms

Polysorbate 80 Atlas E; Armotan PMO 20; Capmul POE-O; Cremophor PS 80; Crillet 4;

Crillet 50; Drewmulse POE-SMO; Drewpone 80K; Durfax 80; Durfax 80K; E433; Emrite

6120; Eumulgin SMO; Glycosperse O-20; Hodag PSMO-20; Liposorb O-20; Liposorb O-

20K; Montanox 80; polyoxyethylene 20 oleate; polysorbatum 80; Protasorb O-20;


CARRIER PROFILE

Ritabate 80; (Z)-sorbitan mono-9-octadecenoate poly(oxy1,2- ethanediyl) derivatives;

Tego SMO 80; Tego SMO 80V; Tween 80.

3 Chemical Name

Polysorbate 80 Polyoxyethylene 20 sorbitan monooleate.

4. Empirical Formula

C64H124O26

5. Molecular Weight

1310

6. Structural Formula :

7. Functional Category:

Dispersing agent; emulsifying agent; nonionic surfactant; solubilizing agent; suspending

agent; wetting agent.

8 Appilication in pharmaceutical Formulation or Technology

Polyoxyethylene sorbitan fatty acid esters (polysorbates) are a series of partial fatty acid

esters of sorbitol and its anhydrides copolymerized with approximately 20, 5, or 4 moles

of ethylene oxide for each mole of sorbitol and its anhydrides. The resulting product is

therefore a mixture of molecules of varying sizes rather than a single uniform compound.

Polysorbates containing 20 units of oxyethylene are hydrophilic nonionic surfactants that

are used widely as emulsifying agents in the preparation of stable oil-in-water

pharmaceutical emulsions. They may also be used as solubilizing agents for a variety of

substances including essential oils and oil-soluble vitamins, and as wetting agents in the

formulation of oral and parenteral suspensions. They have been found to be useful in

improving the oral bioavailability of drug molecules that are substrates for P-glycoprotein.

Polysorbates are also widely used in cosmetics and food products.


CARRIER PROFILE

9.Description

Polysorbates have a characteristic odor and a warm, somewhat bitter taste. At 25°C it is

yellow oily liquid.

.

10 Typical Properties

Table 6.10

Properties of Talc

Properties Range

pH 6.0-8.0

HLB Value 15.0

Specific gravity 1.08

Viscosity 42.5 mPa s

Surface Tension 42.5 mN/m

Acid Value 2.0

Hydroxyl Value 65-80

Moisture Content 3.0

Saponification Value 45-55

Solubility

Soluble in water and ethanol . Insoluble in mineral oil and vegetable oil.


CARRIER PROFILE


Carriers Profile AMLODIPINE - Copy

Documents

Transcript of Carriers Profile AMLODIPINE - Copy