Use of Polyvinyl Alcohol as a Solubility-Enhancing Polymer for Poorly Water Soluble Drug Delivery (Part 1)

Area of Science:

• Pharmaceutical Science
• Polymer Science

Background:

• Polyvinyl alcohol (PVAL) traditionally has limitations for use as a concentration-enhancing polymer due to high melting point, high viscosity, and poor organic solubility.
• KinetiSol® dispersing (KSD) technology enables PVAL for novel pharmaceutical applications.

Purpose of the Study:

• To investigate various grades of PVAL for improving the solubility and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs).
• To assess the impact of polymer molecular weight and degree of hydroxylation on the performance of amorphous dispersions.

Main Methods:

• Creation of solid amorphous dispersions using itraconazole (ITZ) as a model drug at 20% drug loading.
• Characterization of dispersions using differential scanning calorimetry, powder X-ray diffraction, polarized light microscopy, size exclusion chromatography, and dissolution testing.
• In vivo pharmacokinetic study in rats to compare formulation performance against current market itraconazole (ITZ) formulations.

Main Results:

• Different PVAL grades demonstrated varying effects on solubility and bioavailability enhancement.
• The 4-88 grade of PVAL was identified as effective in creating amorphous dispersions with ITZ.
• The PVAL-based amorphous dispersion showed enhanced solubility and bioavailability of itraconazole compared to controls.

Conclusions:

• PVAL, specifically the 4-88 grade, can be effectively utilized with KSD technology to create amorphous solid dispersions.
• This approach significantly enhances the solubility and oral bioavailability of poorly water-soluble drugs like itraconazole.
• The study validates PVAL as a viable polymer for developing advanced drug delivery systems for poorly soluble APIs.