1. PARENTERAL DRUG FORMULATIONS
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2. PARENTERALS
para: outside
enteron: intestine (i.e. beside the intestine)
These are the preparations which are given other than oral routes.
Injections:
These are
Sterile,
Pyrogen free preparations intended to be administered parenterally (outside alimentary tract).

3. Necessities of Parenteral preparations:
Sterility (must)
Pyrogen (must)
Free from particulate matter (must)
Clarity (must)
Stability (must)
Isotonicity (should)
Solvents or vehicles used must meet special purity and other standards.
Restrictions on buffers, stabilizers, antimicrobial preservative. Do not use coloring agents.
Must be prepared under aseptic conditions.
Specific and high quality packaging.

4. General steps involved
1. Cleaning
2. Preparation of bulk products
3. Filtration
4. Filling of solution in or product in ampoule or vial
5. Sealing
6. Sterilization
7. Tests for Quality control

5. Parental Routes of Administration:
Most Common: 1. Subcutaneous (SC; SQ ;Sub Q)
2. Intramuscular (IM)
3. Intravenous (IV)
Others: Intra-arterial (IA)
5. Intrathecal
6. Intraarticular
7. Intrapleural
8. Intracardial
9. Intradermal (Diagnostic)

6. Routes of Parenteral Administration
Subcutaneous (21)
Intravenous (21)
Intramuscular (20)
Intradermal (23)
Intra arterial (20-22)
Epidermis
Dermis
Vein
Subcutaneous
tissue
Artery
Muscle

7. Formulation of Parenteral:
Therapeutic agents
Vehicles
Water
Water miscible vehicles
Non- aqueous vehicles
Added substances (Additives)
Antimicrobials
Antioxidants
Buffers
Bulking agents
Chelating agents
Protectants
Solubilizing agents
Surfactants
Tonicity- adjusting agents

8. Formulation of Parenteral
1. Active Pharmaceutical Ingredients (API):
Antibiotics
Anticancer
Steroids
Vaccines
Antipyretic
Analgesics
Anti- inflammatory
LVP’s like Dextrose, NaCl or combination etc

9. API Profile:
Solubility in different solvents (parentally acceptable solvents / co-solvents)
Partition Coefficient (octanol:water)
pH Solubility
Forced degradation Study

10. API Profile The stability of API (forced degradation study)
Thermal Stress: A 1 mg/mL sample in a 10:90 acetonitrile:water or any suitable solvent mixture and heated to 100°C for 30 minutes and then to be assayed.
Acidic Stress: mixing 0.1 mL of a 10 mg/mL of sample in acetonitrile solution or any suitable solvent with 0.1 mL of either 1 N or 12.1 N HCl and be allowed to react for 24 hours.
Basic Stress: Sample solution in acetonitrile or any suitable solvent be treated with buffered saline having pH of 8.
Oxidative Stress: mixing an equal volume of drug solution in acetonitrile or any suitable solvent with 30% hydrogen peroxide solution and allowed to react for 24 hours.

11. Formulation of Parenteral
2. Solvents:
Water
Should meet compendial requirements
Water miscible vehicles
Ethyl alcohol
PEG PG
Non aqueous vehicles
Fixed oils

12. Formulation of Parenteral
Solvents
Solvents used must be:
Non-irritating
Non-toxic
Non-sensitizing
No pharmacological activity of its own
Not affect activity of medicinal

13. Formulation of Parenteral
3. Added substances (Additives)
Antimicrobials:
Added for fungistatic or bacteriostatic action or
Used to prevent the multiplication of micro-organisms;
concentration
Benzyl alcohol – 10 %
Benzethonium chloride %
Methyl paraben – 0.18 %
Propyl paraben – %
Phenol – 0.5 %

14. Antioxidants: Used to protect product from oxidation
Acts as reducing agent or prevents oxidation
Ex:
A) Reducing agent:
Ascorbic acid – 0.1 %
Sodium bisulphite – 0.15 %
Sodium metabisulphite – 0.15 %
Thiourea %
B) Blocking agents:
Ascorbic acid esters – 0.015%
BHT – 0.02 %
C) Synergistic:
Ascorbic acid , Citric acid , Tartaric acid
D) Chelating agent:
EDTA %

15. Buffers: Factors affecting selection of buffers: EXAMPLES:
Added to maintain pH,
Change in pH may causes degradation of the products
Acetates, citrates, phosphates are generally used.
Factors affecting selection of buffers:
Effective range,
Concentration
Chemical effect on the total product
EXAMPLES:
Acetic acid ,adipic acid, benzoic acid, citric acid, lactic acid
Used in the conc. of 0.1 to 5.0 %

16. Chelating agents: Examples:
Used to form the complex with the metallic ions present in the formulation so that the ions will not interfere during mfg. of formulation.
They form a complex which gets dissolved in the solvents.
Examples:
Disodium edetate %
Disodium calcium edetate %
Tetrasodium edetate %

17. Stabilizers: Examples:
As parenterals are available in solution form they are most prone to unstabilize
Used to stabilize the formulation
Maintain stable
Examples:
Creatinine – %
Glycerin – 1.5 – 2.25 %
Niacinamide – %
Sodium saccharin – %
Sodium caprylate – 0.4 %

18. Solubilizing agents: Examples:
Used to increase solubility of slightly soluble drugs
they acts by any one of the following:
solubilizers,
emulsifiers or
wetting agents.
Examples:
Dimethylacetamide,
Ethyl alcohol
Glycerin
Lecithin
PEG – 40 castor oil
PEG – 300
Polysorbate 20, 40, 80

19. Tonicity- adjusting agents:
Used to reduce the pain of injection.
Buffers may acts as tonicity contributor as well as stabilizers for the pH.
Isotonicity depends on permeability of a living semipermeable membrane
Hypotonic : swelling of cells (enlargement)
Hypertonic: shrinking of cells (reduction)
Example:
Glycerin
Lactose
Mannitol
Dextrose
Sodium chloride
Sorbitol

20. Formulated Product Stability Studies
Finished product stability is tested according to International Conference on harmonization (ICH) guidelines.