SAIF ULLAH KHAN

2. PREPARED BY
MASH' HOOD MAHMOOD KHAN SHAHID
UZAIR
SAIF ULLAH KHAN
D14E121
D14E122
D14E12
3

3. ADDED SUBSTANCES:-
“Added substances or additives are generally
employed in parenteral preparation to enhance its
physical and chemical stability i.e shelf life or esthetic
appearance.”

4. CRITERIA OF ADDED SUBSTANCE:-
• It must be non toxic in quantity administered to the patient
• It should not interfere with therapeutic efficacy nor with the
assay of active therapeutic compound
• It must be prevented from adversely affecting the product

5. TYPES OF PARENTERAL ADDITIVES:-
Antimicrobials
Antioxidants
Buffers
Bulking agent
Chelating agent
Protectants
Solubilizing agent
Surfactants
Tonicity adjusting agents
Antifungal agents
Hydrolysis inhibitors
Antifoaming agents

6. ANTIMICROBIALS AGENTS:-
A suitable preservative system is required in all multiple dose
parenteral products to inhibit the growth of microorganism
accidentally introduced during withdraw of individual doses.
Preservatives may be to single dose parenteral products that are not
terminally sterilized as a sterility assurance measure i.e. to prevent
the growth of any microorganism that could be introduced of there
were any inadvertent breach of asepsis during filling operations

7. EXAMPLE:-
• Benzalkonium chloride
• Benzethonium chloride
• Benzyl alcohol
• Phenol
• Metacresol

8. ANTIOXIDANTS:-
Many drugs in solutions are subject to oxidative degradation. Such reaction
are mediated by free radicals or by molecular oxygen or removal of hydrogen
. Oxidative decomposition is catalyzed by metal, hydrogen and hydroxyl ions.
Drugs possessing a favorable oxidation potential will be especially vulnerable
to oxidation. For example, a great number of drugs are formulated in the
reduced form (e.g. epinephrine,morphine,ascorbic acid,e.t.c.) and are easily
oxidized. By increasing the oxidation potential of the drug oxidation can be
minimized.

9. EXAMPLES:-
. Salts of sulfur dioxide including bisulfite ,
metabisulfite and sulfite are the most common
antioxidant used in aqueous parenterals.

10. BUFFERS:-
Many drugs require a certain pH range to maintain product stability.
Drug stability strongly depend on the pH of the solution. Change in
pH may occur during storage by the following ways:-
• By dissolving gas constituent in the product
• By releasing of constituents from rubber closures or plastic
components in contact with the product
• By dissolving of gas and vapours from airspace in the container
• Reactions within the product
Buffer system for parenterals consist of either a weak base or a salt
of weak base or a weak acid or salt of weak acid

11. EXAMPLES:-
• Acetic acid
• Adipic acid
• Citric acid
• Sodium bicarbonate
• Sodium carbonate

12. CHELATING AGENT:-
Chelating metals are added to complex and thereby inactivate
metals such as copper, iron , zinc that generally catalyze
oxidative degradation of drug molecules. Sources of metal
combination include raw material impurities solvents such as
water, rubber stoppers, and containers and equipment
employed in the manufacturing process.

13. EXAMPLES:-
• Edetate disodium
• Edetate tetrasodium

14. INERT GASES:-
Another means of enhancing the product integrity of oxygen
sensitive medicaments is by displacing the air the solution with
nitrogen or argon. This technique may be made more effective by
first purging with nitrogen or boiling the water to reduce dissolved
oxygen. The container is also purged with nitrogen or argon before
filling and may also be topped off with gas before sealing.

15. SOLUBILIZING, WETTING AGENTS:-
Solubilizing agents are used to increased drug solubility by using non
aqueous solvents
Examples:-
• Polyethlene glycol (PEG)
• Ethyl alcohol(C2H5OH)
• Glycerin
• Lecithin
• povidone

16. SURFACTANTS:-
Surfactants are used :-
• To dispose a water insoluble drugs as a colloidal
dispersion
• For wetting powder
• To prevent crystal growth in a suspension
• To provide acceptable syringability
• For solubilizing steroids and fat soluble vitamins

17. EXAMPLE:-
• Polyethylene
• Sorbitan monooleate

18. TONICITY ADJUSTMENT AGENTS:-
Isotonicity is important for parenteral preparation because the possibility that
the product may penetrate red blood cell and cause hemolysis is greatly
reduced if the solution is isotonic with blood i.e. the cells maintain their tone.
Solution that less osmotic pressure than the blood plasma called hypotonic
and solution that more osmotic pressure than the blood plasma called
hypertonic. When introduce hypotonic solution cell may swell and offers brust
because of diffusion of water into the cell i.e. hemolysis, if introduce
hypertonic solution ,the cell may lose water and shrink. In isotonic solution
the cell maintain their tone and the solution is isotonic with human
erythrocytes.

19. EXAMPLES:-
• Sodium chloride
• Gelatin
• Lactose
• Dextrose
• Sorbitol

20. PROTECTANT:-
Protectants are used:-
• To protect against loss of activity caused by some stress
• To prevent the loss of active ingredients by adsorption to
process equipment or to primary packaging material
Protectants are used in the formulations of proteins.

21. EXAMPLE:-
• Sucrose
• Glucose
• Maltose
• Lactose