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

Abstract

Abstract. Polyvinyl alcohol (PVAL) has not been investigated in a binary formulation as a concentrationenhancing polymer owing to its high melting point/high viscosity and poor organic solubility. Due to the unique attributes of the KinetiSol® dispersing (KSD) technology, PVAL has been enabled for this application and it is the aim of this paper to investigate various grades for improvement of the solubility and bioavailability of poorly water soluble active pharmaceutical ingredients. Solid amorphous dispersions were created with the model drug, itraconazole (ITZ), at a selected drug loading of 20%. Polymer grades were chosen with variation in molecular weight and degree of hydroxylation to determine the effects on performance. Differential scanning calorimetry, powder X-ray diffraction, polarized light microscopy, size exclusion chromatography, and dissolution testing were used to characterize the amorphous dispersions. An in vivo pharmacokinetic study in rats was also conducted to compare the selected formulation to current market formulations of ITZ. The 4-88 grade of PVAL was determined to be effective at enhancing solubility and bioavailability of itraconazole.

Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index

“…Particularly, it was shown Przybyłek et al, 2017) that compounds containing polar OH and COOH groups are excellent methylxanthines solubility enhancers. Solubility increase in the presence of hydrophilic compounds is consistent with many experimental data (Brough et al, 2015;Savjani et al, 2012;Thiry et al, 2017b). It is understandable that hydrophilic excipients will also improve the dissolution profile.…”

“…This is in accord with chemical intuition and pharmaceutical drug delivery strategies (Brough et al, 2015;Ghanbarzadeh et al, 2016;Kalepu and Nekkanti, 2015;Maggi et al, 2013;Sareen et al, 2012;Savjani et al, 2012;Serajuddin, 1999;Sruti et al, 2013) that differences in polarities between drug and excipient is a main driving force toward dissolution. Many examples of such cases can be found in the literature, including cocrystals but also other types of solid mixtures such as inclusion complexes with cyclodextrins (Dua et al, 2011;M Badr-Eldin et al, 2013;Thiry et al, 2017aThiry et al, , 2017b and dispersions with soluble polymers (Brough et al, 2015;Choi and Park, 2017;Ibrahim et al, 2010;Maggi et al, 2013;Six et al, 2004;Thiry et al, 2017a). Noteworthy, Guha et al, (2011), found that APIs can be classified in terms of their kinetic solubility values using different hydrophilicity indices.…”

Development of 3D Printed Tablets by Fused Deposition Modeling Using Polyvinyl Alcohol as Polymeric Matrix for Rapid Drug Release

“…Although not specifically formulated for 3D printing, several other investigators used PVA as the matrix for the solid dispersion of drugs and observed variable miscibility between drugs and polymer by DSC and powder X-ray diffraction (PXRD) analyses. 28,[40][41][42] Thus, it is apparent that the method of preparation and the drug-polymer miscibility are important aspects of using PVA for 3D printing.…”

Investigation of the properties of Ni(OH)2 electrochrome films obtained in the presence of different types of polyvinyl alcohol

“…The paper [23] describes that different grades of PVA as a stabilizer for membrane-bound and membrane-encapsulated ferments can significantly affect the activity of the latter. At the same time, the paper [24] describes that molecular weight and hydrolysis degree of PVA affect bioavailability and solubility of some poorly-soluble drugs. Using model itraconazole as a model drug, it was determined that the use of some grades of PVA is preferable for aqueous media.…”