PHARMACEUTICAL INGREDIENTS

Murat Kizaibek

• Acidifying agent

• Definition:Used in liquid preparations to provide acidic m

edium for product stability

• Examples:

Citric acid

Acetic acid

Fumaric acid

Hydrochloric acid

Nitric acid

• Alkalinizing agent

• Definition:Used in liquid preparations to pr

ovide alkaline medium for product stability

• Examples:

Ammonia solution

Ammonium carbonate

Diethanol amine

Monoethanol amine

Potassium hydroxide

Sodium bicarbonate

Sodium borate

Sodium carbonate

Sodium hydroxide

Trolamine

• Adsorbent

• Definition:An agent capable of holding other molecules onto its surface by physical or chemical (chemisorption) means

• Examples:

Powdered cellulose

Activated charcoal

• Aerosol propellant• Definition:Agent responsible for developing

the pressure within an aerosol container and expelling the product when the valve is opened

• Examples:

Carbon dioxide;

Dichlorodifluoromethane;

Dichlorotetrafluoroethane;

Trichloromonofluoromethane.

• Air displacement

• Definition:Agent employed to displace air in a hermetically sealed container to enhance product stability.

• Examples:

Nitrogen

Carbon dioxide

• Antifungal preservative

• Definition:Used in liquid and semisolid preparations to pr

event growth of fungi. Effectiveness of parabens is usuall

y enhanced by use in combination.

Example:

Butylparaben

Ethylparaben

Methylparaben

Benzoic acid

Propylparaben

Sodium benzoate; Sodium propionate

• Antimicrobial preservative

• Definition:Used in liquid and semisolid preparations to prevent growth of microorganisms

• Examples:

Benzalkonium chloride

• Antioxidant

• Definition:Used to prevent deterioration of prepar

ations by oxidation

• Examples:Ascorbic acid; Ascorbyl palmitate; But

ylated hydroxyanisole; Butylated hydroxytoluene;

Hypophosphorous acid; Monothioglycerol; Prop

yl gallate; Sodium ascorbate; Sodium bisulfite; S

odium formaldehyde;Sulfoxylate;Sodium metabi

sulfite

• Buffering agent

• Definition:Used to resist change in pH upon dilution or addition of acid or alkali

• Examples:Potassium metaphosphate;

Potassium phosphate;monobasic;Sodium acetate;Sodium citrate, anhydrous and dihydrate

• Chelating agent

• Definition:Substance that forms stable water-soluble complexes (chelates) with metals; used in some liquid pharmaceuticals as stabilizers to complex heavy metals that might promote instability. In such use, they are also called sequestering agents

• Examples:

EDTA

• Clarifying agent

• Definition:Used as a filtering aid for its adsorbent qualities

• Examples:Bentonite

• Colorant• Definition:Used to impart color to liquid and solid (e.g., ta

blets and capsules) preparations• Examples:• FD&C Red No. 3

FD&C Red No. 20

FD&C Yellow No. 6

FD&C Blue No. 2

D&C Green No. 5

D&C Orange No. 5

D&C Red No. 8

Caramel

Ferric oxide, red

• Emulsifying agent

• Definition:Used to promote and maintain dispersion of fin

ely subdivided particles of liquid in a vehicle in which it is

immiscible. End product may be a liquid emulsion or sem

isolid emulsion(e.g., a cream)

• Examples:

Acacia

Cetomacrogol

Cetyl alcohol

Glyceryl monostearate

Span 80

Polyoxyethylene 50 stearate

• Encapsulating agent

• Definition:Used to form thin shells to enclose a drug for ease of administration

• Examples:Gelatin

• Flavorant

• Definition:Used to impart a pleasant flavor and often odor to a preparation. In addition to the natural flavorants listed, many synthetic ones are used.

• Examples: Anise oil Cinnamon oil Cocoa Menthol Orange oil Peppermint oil Vanillin

• Humectant

• Definition:Used to prevent drying of preparations, particularly ointments and creams

• Examples:

Glycerin

Propylene glycol

Sorbitol

• Levigating agent

• Definition:Liquid used as an intervening agent to reduce the particle size of a powder by grinding, usually in a mortar

• Examples:

Mineral oil

Glycerin

Propylene glycol

• Ointment base

• Definition:Semi solid vehicle for medicated ointments

• Examples:

Lanolin

Hydrophilic ointment

Polyethylene glycol ointment

Petrolatum

Hydrophilic petrolatum

• Plasticizer

• Definition:Component of film coating solutions t

o make film more pliable,enhance spread of co

at over tablets, beads, and granules

• Examples:

Diethyl phthalate

Glycerin

• Solvent

• Definition:Used to dissolve another substance in prepara

tion of a solution;may be aqueous or not (e.g., oleaginou

s). Cosolvents, such as water and alcohol (hydroalcoholi

c) and water and glycerin, may be used when needed. St

erile solvents are used in certain preparations (e.g., injec

tions)

• Examples:Alcohol; Corn oil; Cotton seed oil; Glycerin; Iso

propyl alcohol; Mineral oil; Oleic acid; Peanut oil; Purified

water; Water for injection; Sterile water for injection; Steri

le water for irrigation

• Stiffening agent

• Definition:Used to increase thickness or hardness of a preparation, usually an ointment

• Examples:

Cetyl alcohol

Cetyl esters wax

Microcrystalline wax

Paraffin

Stearyl alcohol

White wax

Yellow wax

• Suppository base

• Definition:Vehicle for suppositories• Examples:

Cocoa butter

Polyethylene glycols (mixtures)

PEG 3350

• Surfactant (surface active agent)

• Definition:Substances that absorb to surfaces or interfac

es to reduce surface or interfacial tension. May be used

as wetting agents, detergents, or emulsifying agents

• Examples:

Spans

Tweens

• Suspending agent

• Definition:Viscosity-increasing agent used to reduce sedimentation rate of particles in a vehicle in which they are not soluble; suspension may be formulated for oral, parenteral, ophthalmic, topical, or other route

• Examples: Agar Bentonite Carbomer (e.g., Carbopol) Carboxymethylcellulose sodium Hydroxyethyl cellulose Hydroxypropyl cellulose Hydroxypropyl methylcellulose Kaolin Methylcellulose Tragacanth

• Sweetening agent• Definition:Used to impart sweetness to a prepara

tion• Examples:

Aspartame

Dextrose

Glycerin

Mannitol

Saccharin sodium

Sorbitol

Sucrose

• Tablet antiadherents

• Definition:Prevent tablet ingredients from sticking to punches and dies during production

• Examples:

Magnesium stearate

• Tablet binders• Definition:Substances used to cause adhesion

of powder particles in tablet granulations• Examples: Acacia Alginic acid Carboxymethyl cellulose sodium Compressible sugar (e.g.,Nu-Tab) Ethylcellulose Gelatin Liquid glucose Methylcellulose Povidone Pregelatinized starch

• Tablet and capsule diluent• Definition:Inert filler to create desired bulk, flow propertie

s, and compression characteristics of tablets and capsules

• Examples:

Dibasic calcium phosphate

Kaolin

Lactose

Mannitol

Microcrystalline cellulose

Powdered cellulose

Precipitated calcium carbonate

Sorbitol

Starch

• Tablet coating agent

• Definition:Used to coat a tablet to protect against decomp

osition by atmospheric oxygen or humidity, to provide a d

esired release pattern, to mask taste or odor, or for aesth

etic purposes. Coating may be sugar, film, or thick coveri

ng around a tablet. Sugar-coated tablets generally start t

o break up in the stomach. Film forms a thin cover aroun

d a formed tablet or bead. Unless it is enteric, film dissolv

es in the stomach. Enteric coating passes through the sto

mach to break up in the intestines. Some water-insoluble

coatings (e.g., ethylcellulose) are used to slow the releas

e of drug in the gastrointestinal tract.

• Sugar coating • Example: Liquid glucose, Sucrose• Film coating • Example

Hydroxyethyl cellulose

Hydroxypropyl cellulose

Hydroxypropyl methylcellulose

Methylcellulose (e.g., Methocel)

Ethylcellulose (e.g., Ethocel)• Enteric coating• Example

Cellulose acetate phthalate

Shellac (35% in alcohol, pharmaceutical glaze)

• Tablet direct compression excipient

• Definition:Used in direct compression tablet formulations

• Examples:

Dibasic calcium phosphate (e.g., Ditab)

• Tablet disintegrant

• Definition:Used in solid forms to promote disruption of the mass into smaller particles more readily dispersed or dissolved

• Examples:

Alginic acid

Polacrilin potassium (e.g., Amberlite)

Sodium alginate

Sodium starch glycolate

Starch

• Tablet glidant

• Definition:Used in tablet and capsule formulations to improve flow properties of the powder mixture.

• Examples:

Colloidal silica

Corn starch

Talc

• Tablet lubricant

• Definition:Used in tablet formulations to reduce friction during tablet compression

• Examples:

Calcium stearate

Magnesium stearate

Mineral oil

Stearic acid

Zinc stearate

• Tablet or capsule opaquant

• Definition:Used to render a coating opaque. May be used alone or with a colorant

• Examples:Titanium dioxide

• Tablet polishing agent

• Definition:Used to impart an attractive sheen to coated tablets

• Examples:

Carnauba wax

White wax

• Tonicity agent

• Definition:Used to render solution similar in os

motic-dextrose characteristics to physiologic fl

uids, e.g., in ophthalmic,parenteral, and irrigati

on fluids

• Examples:Sodium chloride

• Vehicle

• Definition:Carrying agent used in formulating a v

ariety of liquids for oral and parenteral administr

ation .Generally, oral liquids are aqueous (e.g., s

yrups) or hydroalcoholic (e.g., elixirs). Solutions

for intravenous use are aqueous, whereas intra

muscular injections may be aqueous or oleagino

us.

• Flavored, sweetened

• Examples:

Acacia syrup

Aromatic syrup

Aromatic elixir

Cherry syrup

Cocoa syrup

Orange syrup

Syrup

• Oleaginous

• Examples:

Corn oil

Mineral oil

Peanut oil

Sesame oil

• Sterile

• Examples:

Bacteriostatic sodium chloride injection

• Viscosity-increasing agent• Definition:Used to render preparations more resistant t

o flow. Used in suspensions to deter sedimentation,in ophthalmic solutions to enhance contact time (e.g., methylcellulose), to thicken topical creams, etc.

• Examples: Alginic acid Bentonite Carbomer Carboxymethylcellulose Sodium Methylcellulose Povidone Sodium alginate Tragacanth

Optimization of ingredients and process

• Simplex method• Lagrangian• Response surface methodology• Factorial design• Central composite design• Orthogonal design• Uniform design

powder of sophora AIopecuroides L ． Seed mix 制软材

prilling 、processing

granulemix

press

excipient

1 ％ Magnesium stearate

table 1 the influence of different adhesives on tablet hardness

formula 1 2 3 4

adhesive 10%

Starch

10%PVP（ water ）

10%CMC-Na 10%PVP (Ethanol)

Hardness

（ Kg ）0.68 0.83 0.75 particles de

formed

table 2 the influence of different fillers on tablet hardness

formula 5 6 7 8

fillers starch Pregelatinized starch

lactose 10%PVP ( Ethanol)

Hardness（ Kg ）

0.68 0.77 3.14 3.55

table 3 factor level

Factor level

A [The amount of Microcrstalline cellulose(g)]

80 120 160

A [Concentration of PVP solution （ % ， g/ml)]

10 15 20

table 4 Result of Orthogonal test

Test NO. 　　 A 　　 B

A×B Result

1 2

Ⅰ ⅡTotal

1 2 3 4 5 6 7 8 9 K1

K2

K3

1 1 1 2 2 2 3 3 317.824.224.4

1 2 3 1 2 3 1 2 323.021.821.6

1 2 3 2 3 1 3 1 2 21.422.522.5

1 2 3 3 1 2 2 3 1 22.222.022.2

3.1 2.9 6.02.8 3.1 5.93.2 2.7 5.94.1 4.4 8.54.0 4.1 8.14.2 3.4 8.54.0 3.8 7.83.9 4.2 8.1

R×6 6.6 1.4

1.1 0.2 0.6

table5 Analysis of variance table

variance source SS V MS F P

total variance 5.658

A 4.698 2 2.349 33.562 0.0001

B 0.191 2 0.096 1.366 0.3034

A×B 0.139 4 0.035 0.993 0.4077

error 0.630 9 0.070

table ６　微晶纤维素用量影响苦豆子片硬度的ｑ检验（ｎ＝６）Comparison group

两均数之差 standard

value of q error

Number of group α =0.05 α= 0.01

P

A1andA3 -1.1 0.1074 -10.241 3 4.34 6.33 <0.01

A1andA2 -1.0 0.1074 -9.310 2 3.46 5.24 <0.01

A2andA3 -0.1 0.1074 -9.310 2 3.46 5.24 >0.05

ｑ界值