Use of Polyvinyl Alcohol as a Solubility Enhancing Polymer for Poorly Water-Soluble Drug Delivery (Part 2)

Abstract

Abstract. The KinetiSol® Dispersing (KSD) technology has enabled the investigation into the use of polyvinyl alcohol (PVAL) as a concentration enhancing polymer for amorphous solid dispersions. Our previous study revealed that the 88% hydrolyzed grade of PVAL was optimal for itraconazole (ITZ) amorphous compositions with regard to solid-state properties, non-sink dissolution performance, and bioavailability enhancement. The current study investigates the influence of molecular weight for the 88% hydrolyzed grades of PVAL on the properties of KSD processed ITZ:PVAL amorphous dispersions. Specifically, molecular weights in the processable range of 4 to 18 mPa · s were evaluated and the 4-88 grade provided the highest AUC dissolution profile. Amorphous dispersions at 10, 20, 30, 40, and 50% ITZ drug loads in PVAL 4-88 were also compared by dissolution performance. Analytical tools of diffusion-ordered spectroscopy and Fourier transform infrared spectroscopy were employed to understand the interaction between drug and polymer. Finally, results from a 30-month stability test of a 30% drug loaded ITZ:PVAL 4-88 composition shows that stable amorphous dispersions can be achieved. Thus, this newly enabled polymer carrier can be considered a viable option for pharmaceutical formulation development for solubility enhancement.

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

“…Recently, reports on a novel processing technology based on temperature and high shear force mixing have shown potential in overcoming the limitations associated with conventional hot-melt extrusion and spray-drying techniques ( 143 , 147 , 151 ). More uncommon preparation methods which are not widely used and established industrially for the preparation of amorphous formulations such as supercritical fluid impregnation /solvent-antisolvent ( 84 , 92 , 102 , 149 ), electrospinning /electrospraying ( 72 , 91 , 141 , 153 , 174 ), confined impinging jet ( 107 ) and pressurized gyration ( 161 ) have also been explored even though the applicability in large scale is still a question.…”

“…The temperatures ranged from 2°C to 60°C and the relative humidity varied between 0% and 100%. The duration also varied significantly, with stability studies lasting from 24 h to two years ( 73 , 74 , 81 , 82 , 84 , 86 , 88 , 92 , 93 , 104 , 105 , 109 , 110 , 113 , 115 , 116 , 118 , 120 , 123 , 124 , 126 , 127 , 129 , 130 , 132 , 134 , 135 , 139 , 143 , 146 , 149 , 153 , 158 , 166 , 169 , 172 , 175 , 176 ). While most of the studies did not mention the container used for the physical stability test, a few specified, for example, whether a closed or open container was used ( 88 , 92 , 113 , 123 , 132 , 146 ).…”

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.…”

Expanding the Application and Formulation Space of Amorphous Solid Dispersions with KinetiSol®: a Review

“…Specifically, grades 4-88, 5-88, 8-88, and 18-88 were evaluated by dissolution testing with PVA 4-88 having the best supersaturation properties of the 4 grades analyzed. Drug load dissolution studies showed that drug supersaturation was decreased with increasing drug load (61). These studies demonstrated both the feasibility of processing amorphous solid dispersions containing PVA and the positive benefit for drug supersaturation with PVA 4-88.…”