ADDED SUBSTANCES

Submitted By : Muhammad Basit Mujahid

Submitted To: Dr Ramla Kashif
Sap Id :70101263
Semester : 8th
 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."
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
TYPES OF PARENTERAL ADDITIVES:-
• Antimicrobials
• Antioxidants
• Buffers
• Bulking agent
• Chelating agent
• Protectants
• Solubilizing agent
• Surfactants
• Tonicity adjusting agents
• Antifungal agents
• Hydrolysis inhibitors
• Antifoaming agents
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
EXAMPLE:-
• Benzalkonium chloride
• Benzethonium chloride
• Benzyl alcohol
• Phenol
• Metacresol
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.
EXAMPLES:-
• Salts of sulfur dioxide, including bisulfite, metabisulfite and sulfite are
the most common antioxidant used in aqueous parenterals.
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 vapors 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
EXAMPLES:-
• Acetic acid
• Adipic acid
• Citric acid
• Sodium bicarbonate
• Sodium carbonate
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.
EXAMPLES:-
• Edetate disodium
• Edetate tetrasodium
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.
SOLUBILIZING, WETTING AGENTS:-
• Solubilizing agents are used to increased drug solubility by using non
aqueous solvents
Examples:-
• Polyethylene glycol (PEG)
• Ethyl alcohol (C2H5OH)
• Glycerin
• Lecithin
• povidone
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
EXAMPLE:-
• Polyethylene
• Sorbitan monooleate
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.
EXAMPLE:-
• Sucrose
• Glucose
• Maltose
• Lactose
Thanks for
Your
Attention