Rey T. Chern

A Novel Method of Preparing PLGA Microcapsules Utilizing Methylethyl Ketone

AbstractPurpose. To substitute dichloromethane with a safer solvent, a solvent extraction process using methylethyl ketone (MEK) was developed to prepare poly(d,l-lactide-co-glycolide) microcapsules. Methods. The MEK dispersed phase containing PLGA and progesterone was emulsified in the MEK-saturated aqueous phase (W1) to make a transient oil-in-water (O/W1) emulsion. It was then transferred to a sufficient amount of water (W2) so that MEK residing in polymeric droplets could be extracted effectively into the continuous phase. Results. This solvent extraction process provided the encapsulation efficiency for progesterone ranging from 77 to 60%. The amount of MEK predissolved in W1 as well as the degree of progesterone payload, influenced the encapsulation efficiency. The leaching profile of MEK analyzed by GC substantiated that, upon dispersion of O/W1 to W2, MEK quickly diffused into the continuous phase. Such a rapid diffusion of MEK from and the ingression of water into polymeric droplets produced hollow microcapsules, as evidenced by their SEM micrographs. Conclusions. When solvent extraction/evaporation techniques are employed for preparing PLGA microcapsules, water-immiscibility of a dispersed phase is not an absolute prerequisite to the successful microencapsulation. Adjustment of an initial extraction rate of MEK and formation of a primary transient O/W1 emulsion are found to be very crucial not only for the success of microencapsulation but also for the determination of microcapsule morphology.

The effect of inert atmospheric packaging on oxidative degradation in formulated granules

No HeadingPurpose.Oxidative degradation of drug substances in pharmaceutical products is well documented and is thought to occur in many cases via autoxidative processes involving headspace molecular oxygen in the primary package. Reducing the headspace oxygen concentration inside a package could thus be an option for reducing oxidative degradation in pharmaceutical products. The purpose of this study is to examine the effect of headspace oxygen concentration and relative humidity (RH) on the oxidative degradation of a model pharmaceutical formulation.Methods.Model formulations, including a drug substance known to exhibit oxidative degradation, at two different drug/excipient ratios were packaged in stoppered glass vials maintained at different oxygen concentrations, (from 0% to 20.9%) and headspace relative humidities and were stored at 40°C. The oxidative degradation was quantified as a function of time.Results.The results clearly show dependence of oxidative degradation on headspace oxygen concen-tration, relative humidity, drug loading and time.Conclusions.The results provided insight into the effectiveness of inert atmospheric packaging (IAP) for protecting oxidation-labile products. In light of these observations, a few strategies for practically implementing inert atmosphere packaging are also presented.