Stability considerations in liquid dosage forms extemporaneously prepared from commercially available products.
The pharmacist, both in community and hospital pharmacy practice, is often challenged with the preparation of a liquid dosage form not available commercially for paediatric patients, those adults unable to swallow tablets or capsules and patients who must receive medications via nasogastric or gastrostomy tubes. Recognising the lack of information available to healthcare professionals, a general discussion of the various parameters that may be modified in preparing these dosage forms and a tabulated summary of the dosage forms presented in the literature is described, which, although not exhaustive, will provide information on the formulation and stability of the most commonly prepared extemporaneous liquid dosage forms. An extensive survey of the literature and investigation of 83 liquid dosage forms revealed that stability considerations were of concern for only 7.2% of these liquid dosage forms, extemporaneously prepared from the following commercially available products: captopril, hydralazine hydrochloride, isoniazid, levothyroxine sodium, phenoxybenzamine hydrochloride and tetracycline hydrochloride. Inclusion of the antioxidant, sodium ascorbate in the liquid dosage form for captopril resulted in improved stability at 4 degrees C. Hydralazine hydrochloride, isoniazid and phenoxybenzamine hydrochloride were adversely affected due to interactions with excipients in the formulation, while the effect of the preservative in lowering the pH in a levothyroxine sodium mixture resulted in decreased stability. Interestingly, the instability in these formulations is primarily due to interactions between the drug substance and the excipients rather than degradation of the active pharmaceutical ingredient by standard routes such as oxidation, hydrolysis, photolysis or thermolysis. This low percentage however illustrates the low risk associated with these dosage forms investigated. It may be concluded that when considering the safety and efficacy of liquid dosage forms prepared extemporaneously, it is thus important to consider not only the stability of the drug substance but the entire formulation.
Glass
Beverley D
BD
School of Pharmacy and Molecular Sciences, James Cook University, Townsville, QLD, Australia. Beverley.Glass@jcu.edu.au
Haywood
Alison
A
D004304:Dosage Forms; D004339:Drug Compounding / Q000379:methods* / Q000592:standards; D004355:Drug Stability; D006801:Humans; D019999:Pharmaceutical Solutions / Q000008:administration & dosage* / Q000138:chemical synthesis*; D010595:Pharmacists / Q000592:standards
D004304:Dosage Forms; D019999:Pharmaceutical Solutions