Facile Technology for Extemporaneous Preparation of Long-Acting Injectable Microparticulate Suspensions at the Patient Side.

In this study, we present an innovative and facile in situ approach for extemporaneous preparation of sterile microparticles. An amazingly simple approach, in situ technology circumvents the stability, and scale up challenges as well as sterilization issues associated with long-acting particulate systems. Monophasic preconcentrates of donepezil base (DPZ), a model drug with a biodegradable polymer poly (DL-lactide-co-glycolide) (PLGA), with stabilizer were prepared by simple solution and sterilized by filtration (0.22 micron). The sterile preconcentrates when added to aqueous dextrose solution (total volume < 3 mL) generated ready-to-inject DPZ PLGA microparticles (DPZ-PLGA-MP) with high reproducibility, entrapment efficiency (> 80%), and size ~ 80 micron. DPZ micro suspension (DPZ-MS) with high precipitation efficiency (> 90%) and size ~ 80 micron was obtained in a similar manner omitting PLGA. XRD and DSC study confirmed decreased crystallinity in the presence of PLGA. No interaction between PLGA and DPZ was evident in the FTIR study. The microparticulate dispersions exhibited good in vitro injectability when tested using the texture analyzer (force < 5 N). When evaluated using the dialysis bag method (Himedia 12-14 kDa molecular weight cutoff), both microparticulate formulations exhibited controlled release up to 1 week in vitro. Further, low burst release of ~ 10% at the end of 6 h in the ex vivo chicken muscle study proposes great promise. Our data propose the facile extemporaneous generation of microparticles as a practical and promising approach for development of long-acting injectables. This facile approach could serve as platform technology for other drug candidates.

Lipid Architectonics for Superior Oral Bioavailability of Nelfinavir Mesylate: Comparative in vitro and in vivo Assessment.

Nelfinavir mesylate (NFV), a human immunodeficiency virus (HIV) protease inhibitor, is an integral component of highly active anti retro viral therapy (HAART) for management of AIDS. NFV possesses pH-dependent solubility and has low and variable bioavailability hampering its use in therapeutics. Lipid-based particulates have shown to improve solubility of poorly water soluble drugs and oral absorption, thereby aiding in improved bioavailability. The current study compares potential of vesicular and solid lipid nanocarriers of NFV with drug nanocrystallites and microvesicular systems like cochleates in improving bioavailability of NFV. The paper outlines investigation of systems using in vitro models like in vitro lipolysis, in vitro release, and permeation through cell lines to predict the in vivo potential of nanocarriers. Finally, in vivo pharmacokinetic study is reported which provided proof of concept in sync with results from in vitro studies. Graphical Abstract ᅟ.