1. Evaluation of polycarbophil coated liposomes and membrane permeation of free and liposomal drugs, 2. In vitro-in vivo evaluation of nicardipine HCl sustained-release formulations

摘要

An evaluation of polycarbophil coated liposomes and nicardipine HCl oral sustained-release formulations are detailed and explained. Polycarbophil coated liposomes were characterized for their drug release, loss of entrapped drug, and membrane permeation. Weights of liposomes during incubation with polycarbophil increased as a function of time. The three model drugs entrapped in liposomes were insulin, dyphylline, and hydrocortisone. Rates of drug release from liposomes were not significantly controlled by the polycarbophil coating. Loss of the entrapped insulin (high MW) was reduced when 1-1.5% polycarbophil solution was applied as coating over the liposomes. In contrast, loss of the entrapped dyphylline and hydrocortisone (low MW) was not affected by polycarbophil coating. Low amounts of insulin, dyphylline, or hydrocortisone were transported across an ethylenevinylacetate membrane in membrane permeation studies. The amounts of drug, entrapped in liposomes, penetrated through the membrane were too low to detect. Polycarbophil coated liposomes may be a promising drug carrier for topical application.;Nicardipine HCl sustained-release products were formulated and evaluated in vitro and in vivo. Appropriate methods and dissolution media for in vitro dissolution testing were investigated and selected. Both enzyme-free simulated gastric and intestinal fluids were required for dissolution testing of sustained-release drug products. Release rates of nicardipine HCl using USP basket or paddle at 50 RPM were comparable to Bio-Dis$spcircler$ at 5 or 10 DPM. Bio-Dis$spcircler$ was the most convenient method, and was therefore selected for product evaluation.;Nicardipine HCl sustained-release products consisted of 75% sustained-release beads and 25% immediate-release powder. Rates of drug release from the beads were controlled by percentages of ethylcellulose used in a spray layering process, but not significantly affected by incorporation of PVP at 10-15%. Rates of drug release were retarded by overcoating with ethylcellulose. Diluent incorporated in immediate-release powder had an influence on flow properties of powder.;A newly developed nicardipine HCl product was tested for bioequivalence with Cardene$spcircler$ SR. Statistical two one-sided t-test indicated that the two products could not be concluded as being bioequivalent. In vitro/in vivo correlation of percentages of drug release was found after the in vitro time scale was corrected.