Comparison of HPMC based polymers performance as carriers for manufacture of solid dispersions using the melt extruder.

Preparation of amorphous solid dispersions using hot-melt extrusion process for poorly water soluble compounds which degrade on melting remains a challenge due to exposure to high temperatures. The aim of this study was to develop a physically and chemically stable amorphous solid dispersion of a poorly water-soluble compound, NVS981, which is highly thermal sensitive and degrades upon melting at 165 °C. Hydroxypropyl Methyl Cellulose (HPMC) based polymers; HPMC 3cps, HPMC phthalate (HPMCP) and HPMC acetyl succinate (HPMCAS) were selected as carriers to prepare solid dispersions using hot melt extrusion because of their relatively low glass transition temperatures.

Application of surface area measurement for identifying the source of batch-to-batch variation in processability.

The primary goal of this study was to evaluate the use of specific surface area as a measurable physical property of materials for understanding the batch-to-batch variation in the flow behavior. The specific surface area measurements provide information about the nature of the surface making up the solid, which may include defects or void space on the surface. These void spaces are often present in the crystalline material due to varying degrees of disorderness and can be considered as amorphous regions.

Combination antifungal therapy involving amphotericin B, rapamycin and 5-fluorocytosine using PEG-phospholipid micelles.

Purpose: Rapamycin and 5-fluorocytosine (5-FC) are antifungal agents with unique mechanisms of activity, with potential for cooperative interaction with AmB. Combination antifungal therapy involving conventional AmB has been restricted by poor physical stability and compatibility with antifungal drugs and vehicles.

Methods: AmB and rapamycin were encapsulated in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy poly(ethylene glycol) (PEG-DSPE) micelles using a solvent evaporation method.

Effect of cholesterol on the release of amphotericin B from PEG-phospholipid micelles.

Micelles formed from PEG-DSPE solubilize high levels of the poorly water-soluble antifungal amphotericin B (AmB). AmB release from PEG-DSPE micelles is slow in buffer but remarkably rapid in the presence of bovine serum albumin (BSA). Sequential changes in the absorbance spectrum of AmB in PEG-DSPE micelles point to a rapid dissociation of incorporated drug in the presence of BSA.

Poly(ethylene glycol)-b-poly(epsilon-caprolactone) and PEG-phospholipid form stable mixed micelles in aqueous media.

Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG(5000)-b-PCL(x)) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy poly(ethylene glycol) (PEG-DSPE), possess small size and high thermodynamic stability, raising their potential as long circulating carriers in the context of delivery of antineoplastic and antibiotic drugs. Formation of mixed polymeric micelles was confirmed using size exclusion chromatography and 1H NMR NOESY. Steady-state fluorescence measurements revealed depressed critical micellar concentrations indicative of a cooperative interaction between component hydrophobic blocks, which was quantified using the pseudophase model for micellization.