Added substances used in parenterals.

2. Presented To
MA’AM MISBAH SULTANA

3. Presented By
H.Noman Ahmad ( D14E117) H.Sohail Fayyaz (D14E107)
Umair Akbar (D14E127) Munib Ahmed ( D14E114)
Hanzla Arshad ( D14E126) Talha Raza (D14E108)

4. ADDED SUBSTANCES

5. INJECTIONS
Sterile microorganisms and pyrogen free
preparation intended to be administered
parentally.

6. ADDED SUBSTANCES
 Suitable substances added to official preparations intended for injection for
the purpose of increasing their stability or usefulness.
 Provided substances are not in interdicted in the individual monograph, and
are harmless in the amounts administered and do not interfere with the
therapeutic efficacy of the preparation or with the specified assays and tests.

7. Antimicrobial Antioxidant
Buffers Bulking Agents
Chelating Agents Protectants
Solubilizing Agents Surfactants
Tonicity Adjusting Agents Antifungal Agents
Hydrolysis Inhibitor Antifoaming Agents

8. BUFFERS
Some substances like proteins degrade with the change in pH. So these are
used for chemical stability of product. Capacity of buffer should be low.
E.g
Citric acid ( 0.5%)
Lactic Acid ( 0.1%)

9. TONICITY ADJUSTERS
These are used to make solutions isotonic with the body fluids. small volume
parenteral intended for the IV preparations need not be maintained but parenteral
that deliver into spinal fluid and ophthalmic must be isotonic.
For sub cutaneous preparations,isotonicity maintaince reduce irritation.
Ex:electrolytes and mono/di saccharides.

10. ANTI-OXIDANTS
Many drugs are prone to oxidation and to protect them, antioxidants
are used.
E.g: sodium bisulfide
EDTA sodium salt increases the activity of antioxidants.
Methods to prevent oxidation:
Removing the oxygen present in the soil by passing the inert gas.
The containers in which the products will transform should be
deaerated.

11. ANTI MICROBIAL AGENTS
USP suggests the addition of bacteriostatic and fungiststic antimicrobials to
parenteral formulations.
And the concentration of parenteral should be enough that they should not
allow micro organisms development when the product is drawed and
during the usage.
E.g.
Phenyl mercuric acetate-0.01%
Thiomeral-0.01%
Benzothenium chloride-0.01%
Phenol and cresol-0.5%

12. Agents with antimicrobial activity must be added to preparation packaged
in multiple dose containers unless prohibited by compendial mono-graph
or unless the drug itself is bacteriostatic.
E.g
Methohexital Sodium for injection and most of the cytotoxic anticancer
products.

13. SOLUBLIZERS
Aids in increasing the solubility of the drug in the solvent
system.

14. They enhance the solubility of the drugs.
Ex: Cyclo dextrins, Tween twenty and Tween eighty are complexing
agents and Surfactants respectively.
Tonicity adjusters make the preparation isotonic to body fluids to
prevent irritation.
Ex: Sodium Chloride, Dextrose.
COMPLEXING AGENTS AND SURFACTANTS

15. Added to complex and thereby, inactive materials copper, iron etc.
These generally catalyze oxidative degradation of drug molecule.
CHELATING AGENTS
Additive Concentration Range (%)
Edetate disodium 0.00368-0.05

16. COMPETITIVE BINDERS
They are used to prevent the interaction between proteins and
glassware.
Preservatives prevent the growth of micro organisms.
Care must be taken while selecting the added substance as they can
induce reaction that may inactivate API

17. Protectants are used
to protect against loss of activity
to prevent loss of active ingredients by absorption
process equipment .
Usually primarily in protein formulation.
Sucrose , Glucose
PROTECTANTS

18. Another means of enhancing the product integrity of oxygen
medicaments is by displacing air with solution with nitrogen or
argon.
INERT GASES

19. Used
to dispose water insoluble drug
for wetting powder
to prevent crystal growth
E.g Polyethylene (0.1-0.5%)
SURFACTANTS

20. OTHER ADDED SUBSTANCES
SUSPENDING AGENTS
Gelatin (2%)
Pectin (0.2%)
STABILIZERS
Glycine ( 1.5-2.25)
Creatinine ( 0.5-0.8)
Niacinamide ( 1.25-2.25)