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