Stability of nonaqueous suspension formulations of plasma derived factor IX and recombinant human alpha interferon at elevated temperatures.

Purpose: To identify a suitable nonaqueous, parenterally acceptable suspending vehicle whereby a therapeutic protein is delivered as a stable flowable powder, making it amenable to delivery from sustained delivery systems maintained at body temperature.

Methods: Formulations of plasma derived Factor IX (pdFIX) and recombinant human alpha interferon (rhalpha-IFN) were formulated as dry powders, suspended in various vehicles (perfluorodecalin, perfluorotributylamine, methoxyflurane, polyethylene glycol 400, soybean oil, tetradecane or octanol) and stored at 37 degrees C. Stability was assessed by size exclusion chromatography, reverse phase chromatography, ion exchange chromatography, and bioassay, and was compared to the stability of dry powder formulations stored at 37 degrees C and -80 degrees C.

Identification of antioxidants for prevention of peroxide-mediated oxidation of recombinant human ciliary neurotrophic factor and recombinant human nerve growth factor.

Peroxides present in non-ionic surfactants used to stabilize certain recombinant protein formulations (e.g. polysorbate 80) can result in the oxidative degradation of proteins.

Quantitative evaluation of the stability and delivery of interleukin-1B by infusion.

The stability and delivery of IL-1 beta has been characterized in a polypropylene based syringe pump infusion system and in polyvinyl chloride based infusion bags, at concentrations ranging from 100 ng/mL to 1 microgram/mL. At higher concentrations (1 microgram/mL), minimal drug loss was observed in both systems. At low doses (100 ng/mL) in the syringe-pump system, the addition of 1% human serum albumin was necessary to prevent significant drug absorption to the polypropylene drug reservoir.

Transdermal drug delivery: problems and possibilities.

Transdermal drug delivery has, in recent years, attracted considerable interest. However, despite the obvious advantages of this novel route of drug administration to achieve systemic therapeutic effect, there remain important, and sometimes severe, limitations on the physiochemical and pharmacological properties of the agent to be delivered. This article reviews the present status and accomplishments of transdermal drug delivery.