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

被引：64
作者：
Brough, Chris [1 ,2 ]
Miller, Dave A. [2 ]
Keen, Justin M. [2 ]
Kucera, Shawn A. [3 ]
Lubda, Dieter [3 ]
Williams, Robert O., III [1 ]
机构：
[1] Univ Texas Austin, Coll Pharm, Div Pharmaceut, 1 Univ Stn,Campus Mail Code A1902, Austin, TX 78712 USA
[2] DisperSol Technol LLC, 111 W Cooperat Way,Bldg 3, Georgetown, TX 78626 USA
[3] Merck KGaA, Frankfurter Str 250, D-64293 Darmstadt, Germany
来源：
AAPS PHARMSCITECH | 2016年 / 17卷 / 01期
关键词：
itraconazole; KinetiSol (R) dispersing; polyvinyl alcohol; PVAL; 4-88; solid amorphous dispersions; HOT-MELT EXTRUSION; AMORPHOUS SOLID DISPERSIONS; CONTROLLED-RELEASE; ITRACONAZOLE; DISSOLUTION; FORMULATION; BIOAVAILABILITY; PERFORMANCE; ACETATE; SUPERSATURATION;
D O I：
10.1208/s12249-015-0458-y
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Polyvinyl alcohol (PVAL) has not been investigated in a binary formulation as a concentration-enhancing polymer owing to its high melting point/high viscosity and poor organic solubility. Due to the unique attributes of the KinetiSol (R) 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.
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收藏
页码：167 / 179
页数：13
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