STERILE DOSAGE FORMS
Sterile dosage forms are those which are free from any microorganisms, dust, fibres, and foreign particles, and should be isotonic. Parenteral preparations as name suggests (par+enteral) are those which are administered other than enteral routes. Enteral route involves esophagus, stomach, intestines but parenteral route bypasses all these. Sterile dosage forms include parenteral preparations and ophthalmic preparations. Parenteral preparations include Injections, transfusions fluids, sterile suspensions, sterile solids, sterile solutions or emulsions. Ophthalmic preparations include eye drops, eye lotions, eye ointments, eye gels, eye suspensions, contact lens solutions.
Parenteral preparations can be divided into small volume parenterals and large volume parenterals.
Small volume (SVPs) according to U.S.P “an injection that is packaged in containers labelled as containing 100ml or less”.
Large volume parenterals (LVPs) according to FDA are aqueous solutions which are supplied in volumes of at least 100ml with sizes of 250ml, 500ml, 1000ml and more. Examples are sodium chloride infusion, ringers, dextrose, plasma expanders etc.
IDEAL PROPERTIES OF STERILE DOSAGE FORMS
Preparations of parenteral products and ophthalmic products involve various considerations:
- STERILITY: 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 to cornea.
- ISOTONICITY: 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 temperature.
- FREE FROM FOREIGN PARTICLES: These products must be free from foreign particles, dust, fibres and must pass clarity test.
- pH OF OPHTALMIC FORMULATIONS: pH of tears is about 7.4. pH plays crucial role in therapeutic activity, solubility, stability and comfort to the patient.
- STABILITY: Physical and chemical stability of sterile formulations should be maintained during storage.
TYPES OF PARENTERAL PREPARATIONS
- TRANSFUSION FLUIDS: Parenteral solutions which are administered by intravenous route for example. Sodium chloride, ringers, dextrose.
- SOLUTIONS/EMULSIONS OF MEDICAMENTS FOR INJECTIONS: commonly used as injections and available in single dose containers or multiple dose containers. For example, diclofenac sodium, dexamethasone.
- STERILE SOLIDS: These drugs are supplied as dry sterile solids which are dissolved in a suitable solvent for administration into the body. These are available in dry solids because drugs are not stable in solution form. For example benzyl penicillin G sodium injection.
- STERILE SUSPENSIONS: sterile suspension of drugs in a suitable solvent and are administered by intramuscular route for example hydrocortisone suspension, methylprednisolone.
FORMULATION OF PARENTERAL PREPARATIONS
Following substances are added in the formulation of stable product.
- Solubilising agents
- Antibacterial agents
- Buffering agents
- Chelating agents
- Emulsifying, suspending and wetting agents
- Tonicity factors
In aqueous vehicle water is used which is well tolerated by body. It is used as
- Water for injection
- Water for injection free from carbon dioxide
- Water for injection free from dissolved air.
Water for injection should be free from pyrogens, volatile and non-volatile impurities.
Commonly used non-aqueous vehicles are alcohols and oils. In oils fixed oils such as almond oil, arachis oil, sesame oil are use as vehicle. These are used when depot effect of drug is needed or when drug is insoluble in water.
Adjuvants are used to maintain stability or increase the quality of formulation. These should be used when necessary.