5. Ideal properties of sterile dosage forms
Sterile preparations should be free from all types of microorganisms.
Ophthalmic formulations must be especially free from Pseudomonas aeruginosa, gram negative
bacteria which is commonly found in ophthalmic formulations and can cause serious infections
Parenteral preparations should be isotonic with blood plasma and body fluids.
Ophthalmic formulations must be isotonic with lachrymal secretions.
Free from pyrogens:
Sterile formulations must be free from pyrogens and toxins.
These products must pass pyrogen test as pyrogens are responsible for rise in body
6. Ideal properties of sterile dosage forms
Free from foreign particles:
These products must be free from foreign particles, dust, fibres and must pass clarity
pH of ophthalmic formulations:
pH of tears is about 7.4. pH plays crucial role in therapeutic activity, solubility, stability
and comfort to the patient.
Physical and chemical stability of sterile formulations should be maintained during
9. Categories of parenteral preparations
The different categories of parenteral preparations include:
Powders for injections or intravenous infusions;
Concentrates for injections or intravenous infusions;
10. Vehicles for Injection
Frequently, isotonic (to blood) to which drug may be added at time of use.
Portion of the vehicle in the formulation,
used primarily to effect solubility of drugs and/or reduce hydrolysis
ethyl alcohol; polyethylene glycol (liquid) and propylene glycol
Fixed oils (vegetable origin, and rancid resistance) used in hormone preparations
11. Aqueous vehicles
Water for Injection (WFI) USP
Sterile Water for Injection (SWFI)
Bacteriostatic Water for Injection USP
Sterile Water for Irrigation USP
Sterile Water for Inhalation USP
12. Water for Injection (WFI) USP
Highly purified water used as a vehicle for injectable
preparations which will be subsequently sterilized.
USP requirement: NMT 10 ppm (1 mg/100 ml) of total
pH of 5.0 – 7.0 .
WFI may be prepared by either distillation or reverse
Stored in chemically resistant tank.
Used as solvent for preparation of parenteral solutions.
It is not required to be sterilized and pyrogen free.
It is intended to be used within 24 hours after collection.
The water should be collected in sterile and pyrogen free
Specifications for WFI as per USP
13. Sterile Water for Injection (SWFI)
Sterile Water for Injection is Water for Injection packaged and rendered sterile.
Is water for injection that is sterilized and packaged in single dose container of type1 and 2 glass.
It is used for extemporaneous prescription compounding and as a sterile diluent for parenteral
It may also be used for other applications when
Access to a validated water system is not practical, or
Where only a relatively small quantity is needed.
Sterile Water for Injection is packaged in single-dose containers not larger than 1 L.
Multiple- dose containers not exceeding 30 ml.
They are permitted to contain higher levels of solid than WFI because of possible leaching.
Used for washing wounds, surgical incisions or body tissues.
Why TDS in SWFI
is more than
14. Bacteriostatic Water for Injection USP
Water for Injection, packaged and rendered sterile, to which one or more suitable
antimicrobial preservatives are added or Is sterile water for injection that contains one
or more suitable antimicrobial agents.
Sterile water containing 0.9% benzyl alcohol that is used to dilute or dissolve
It is intended to be used as a diluent in the preparation of parenteral products.
These are typically for multi-dose products that require repeated content withdrawals.
It also packaged in single or multiple dose container of type 1 and 2 glass.
It may be packaged in single-dose or multiple-dose containers not larger than 30 mL.
15. Sterile Water for Irrigation USP
Water for Injection packaged and sterilized in single-dose containers which may be
larger than 1 L.
Is water for injection that is sterilized and suitably packaged.
They allow rapid delivery of their contents.
Due to its usage, Sterile Water for Irrigation is not required to meet Particulate Matter
It contains no antimicrobial agents or other added substances.
16. Sterile Water for Inhalation USP
Is Water for Injection that is packaged and rendered sterile.
It is intended for use in inhalators and in the preparation of inhalation solutions.
This monograph has no requirement to meet.
It carries a less stringent specification for bacterial endotoxins than Sterile Water for
Therefore is not suitable for parenteral applications.
17. Water-miscible vehicles
A number of solvents that are miscible with water have been used as a portion of the
vehicle in the formulation of parenterals.
These solvents are used to solubilize certain drugs in an aqueous vehicle and to
The most important solvents in this group are ethyl alcohol, liquid polyethylene glycol
and propylene glycol.
Ethyl alcohol is used in the preparation of solutions of cardiac glycosides and the
glycols in solutions of barbiturates, certain alkaloids, and certain antibiotics.
Such preparations are given intramuscularly.
There are limitations with the amount of these co-solvents that can be administered,
due to toxicity concerns, greater potential for hemolysis, and potential for drug
precipitation at the site of injection.
Formulation scientists needing to use one or more of these solvents must consult the
literature and toxicologists to ascertain the maximum amount of co-solvents allowed
for their particular product.
18. Non-Aqueous Vehicles
The most important group of non-aqueous vehicles is the fixed oils.
The USP provides specifications for such vehicles, indicating that the fixed oils must
be of vegetable origin so they will metabolize, will be liquid at room temperature,
and will not become rancid readily.
The USP also specifies limits for the free fatty acid content, iodine value, and
saponification value (oil heated with alkali to produce soap, i.e., alcohol plus acid
The oils most commonly used are corn oil, cottonseed oil, peanut oil, and sesame oil.
Fixed oils are used as vehicles for certain hormone (e.g., progesterone, testosterone,
deoxycorticosterone) and vitamin (e.g., Vitamin K, Vitamin E) preparations.
The label must state the name of the vehicle, so the user may beware in case of
known sensitivity or other reactions to it.
Added for fungistatic or bacteriostat action or concentration.
Used to prevent the multiplication of micro-organisms.
Benzyl alcohol -- 0.5 – 10 %
Benzethonium chloride -- 0.01 %
Methyl paraben -- 0.01 – 0.18 %
Propyl paraben -- 0.005 – 0.035 %
Phenol -- 0.065 – 0.5 %
Multidose containers must have preservatives unless prohibited by monograph.
Large volume parenteral must not contain preservative b’coz it may be dangerous
to human body if it contain in high doses.
Added to maintain pH,
Change in pH may causes degradation of the products
Acetates, citrates, phosphates are generally used.
Factors affecting selection of buffers:
Chemical effect on the total product
Acetic acid, adipic acid, benzoic acid, citric acid, lactic acid
Used in the conc. of 0.1 to 5.0 %
As parenterals are available in solution form they are most prone to unstabilize.
Used to stabilize the formulation
Creatinine – 0.5- 0.8 %
Glycerin – 1.5 – 2.25 %
Niacinamide – 1.25 -2.5 %
Sodium saccharin – 0.03 %
Sodium caprylate – 0.4 %
23. Chelating agents
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.
Disodium edetate – 0.00368 - 0.05 %
Disodium calcium edetate - 0.04 %
24. Solubilizing agents
Used to increase solubility of slightly soluble drugs
They acts by any one of the following:
Dimethylacetamide, Ethyl alcohol, Glycerine, Lecithin, PEG – 40 + Castor oil, PEG – 300,
Polysorbate 20, 40, 80
25. 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.
26. 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)
Glycerin, Lactose, Mannitol, Dextrose, Sodium chloride, Sorbitol
to dispose a water-insoluble drug 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.
Polyethylene 0.1 to 0.5%
Sorbitan monooleate 0.05 to 0.25%
Used to protect against loss of activity caused by some stress
Used to prevent loss of active ingredients by adsorption to process equipment
or to primary packaging materials
Protectants primarily used in protein formulations.
Sucrose, glucose, lactose, maltose, trehalose (2 to 5%)
Human serum albumin (0.1 to 1%)