Lecture PK-1: Formulation & Requirements of Parenteral Medicines 1 Flashcards
alimentary canal
a continuous passage starting from the mouth and ending at the anus, which carries food through different parts of the digestive system and allows waste to exit the body
parenteral
Located outside the alimentary canal.
Taken into the body or administered in a manner other than through the digestive tract, as by intravenous or intramuscular injection
intravenous ( IV)
rapid/predictable response
can be large or small volumes
solutions or emulsions
Intramuscular (IM or i.m.)
into a muscle; small volume of injection; relatively rapid absorption; can be used for controlled release formulations
Intradermal (ID or i.d.)
between the epidermis and dermis; up to 200 µL; allergy tests, some vaccines
Subcutaneous (SC or s.c.)
slower onset of action and sometimes <absorption of drugs; injection around 1 mL; route of choice for administration of insulin; can be used for implants
Intrathecal (IT or i.t.)
into the cerebrospinal fluid
Epidural
outside the dura
Intra-articular (IA or i.a.)
into the synovial fluid of a joint cavity
Intracardiac (IC or i.c.)
into the muscles of the heart;
only performed in emergencies
Intra-arterial
similar to IV, but riskier so seldom used
Intraocular
into the eye
Advantages of Parenteral Formulations
Immediate physiological response (IV route) for acute medical situations, e.g., cardiac arrest, anaphylactic shock, asthma
Unconscious/uncooperative patients, patients with nausea/vomiting
Control of dosage and frequency of administration by trained medical staff (an exception being self-administration of insulin)
Requirement for localized effect
Correction of electrolytes (using infusion solutions)
Range of drug release profiles
Total parenteral nutrition (TPN)
Disadvantages of Parenteral Formulations
More complicated manufacturing process (aseptic technique); cost
Skill of administration: dosage form administered by correct route
Pain on administration, possible side-effects from rapid Cp elevation
Allergy to the formulation (rapid, intense reaction)
Difficult to reverse the effects of drugs that have been administered parenterally
Formulation Considerations- Physicochemical properties of drug
Good solubility = solution
Moderate solubility = solution (with co-solvents), or suspension - caution: potential recrystallization
Low solubility = suspension
Formulation Considerations - Excipients
Co-solvents
Similar as for pharmaceutical solutions
Potentially greater toxicity when administered parenterally (toxicity IV> IM = SC)
Glycerol, ethanol, propylene glycol
Surfactants
As in solutions, suspensions
Non-ionic surface-active agents - e.g., Tween series (esp. for biologicals), poloxamers
Buffers
Acetate, citrate or phosphate salts to maintain correct pH
Preservatives
Must be included in multiple dose parenterals - e.g., benzalkonium chloride, benzoic acid, benzyl alcohol, cresol
Anti-oxidants
E.g., ascorbic acid and α-tocopherol (vitamins C and E; aqueous and oil-based preparations, respectively); sodium metabisulphite, sodium bisulphite; citric acid, EDTA (chelators)
Tonicity agents
Sodium chloride or dextrose
Colligative Properties
Properties of solutions that are dependent on the ratio of solute particles to solvent particles in the solution, not the identity of the solute:
Vapour pressure depression
Boiling point elevation
Freezing point depression
Osmotic pressure
Extensive Properties
Depend on the size of the sample e.g. volume, mass.
Intensive Properties
Characteristic of the substance, independent of sample size e.g. density and concentration.
Addition of a non-volatile solute to a solvent (water)
reduces the vapour pressure above the liquid
