Micronized powders of a poorly water soluble drug produced by a spray-freezing into liquid-emulsion process

被引:56
作者
Rogers, TL
Overhoff, KA
Shah, P
Santiago, P
Yacaman, MJ
Johnston, KP
Williams, RO
机构
[1] Univ Texas, Coll Pharm, Austin, TX 78712 USA
[2] Univ Texas, Dept Chem Engn, Austin, TX 78712 USA
基金
美国国家科学基金会;
关键词
spray-freezing into liquid; dissolution enhancement; danazol; emulsion; micronization; particle engineering;
D O I
10.1016/S0939-6411(02)00193-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The purpose of this paper is to investigate the influence of the emulsion composition of the feed liquid on physicochemical characteristics of drug-loaded powders produced by spray-freezing into liquid (SFL) micronization, and to compare the SFL emulsion process to the SFL solution process. Danazol was formulated with polyvinyl alcohol (MW 22,000), poloxamer 407, and polyvinylpyrrolidone K-15 in a 2:1: 1:1 weight ratio (40% active pharmaceutical ingredient (API) potency based on dry weight). Emulsions were formulated in ratios up to 20: 1: 1:1 (87% API potency based on dry weight). Ethyl acetate/water or dichloromethane/water mixtures Were used to produce o/w emulsions for SFL micronization, and a tetrahydrofuran/water mixture was used to formulate the feed solutions. Micronized SFL powders were characterized by X-ray diffraction, surface area, scanning and transmission electron microscopy, contact angle and dissolution. Emulsions containing danazol in the internal oil phase and processed by SFL produced micronized powders containing amorphous drug. The surface area increased as drug and excipient concentrations were increased. Surface areas ranged from 8.9 m(2)/g (SFL powder from solution) to 83.1 m(2)/g (SFL powder from emulsion). Danazol contained in micronized SFL powders from emulsion and solution was 100% dissolved in the dissolution media within 2 min, which was significantly faster than the dissolution of non-SFL processed controls investigated (<50% in 2 min). Micronized SFL powders produced from emulsion had similar dissolution enhancement compared to those produced from solution, but higher quantities could be SFL processed from emulsions. Potencies of up to 87% yielded powders with rapid wetting and dissolution when utilizing feed emulsions instead of solutions. Large-scale SFL product batches were manufactured using lower solvent quantities and higher drug concentrations via emulsion formulations, thus demonstrating the usefulness of the SFL micronization technology in pharmaceutical development. (C) 2003 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:161 / 172
页数:12
相关论文
共 32 条
[11]   Oral bioavailability of a poorly water soluble HIV-1 protease inhibitor incorporated into pH-sensitive particles:: effect of the particle size and nutritional state [J].
De Jaeghere, F ;
Allémann, E ;
Kubel, F ;
Galli, B ;
Cozens, R ;
Doelker, E ;
Gurny, R .
JOURNAL OF CONTROLLED RELEASE, 2000, 68 (02) :291-298
[12]   THE CHARACTERIZATION OF STRUCTURE IN SUSPENSIONS [J].
DONALDSON, CC ;
MCMAHON, J ;
STEWART, RF ;
SUTTON, D .
COLLOIDS AND SURFACES, 1986, 18 (2-4) :373-393
[13]   Physical properties and stability of two emulsion formulations of propofol [J].
Han, JH ;
Davis, SS ;
Washington, C .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2001, 215 (1-2) :207-220
[14]   Using freezing and drying techniques of emulsions for the microencapsulation of fish oil to improve oxidation stability [J].
Heinzelmann, K ;
Franke, K .
COLLOIDS AND SURFACES B-BIOINTERFACES, 1999, 12 (3-6) :223-229
[15]   Improvement of dissolution rates of poorly water soluble APIs using novel spray freezing into liquid technology [J].
Hu, JH ;
Rogers, TL ;
Brown, J ;
Young, T ;
Johnston, KP ;
Williams, RO .
PHARMACEUTICAL RESEARCH, 2002, 19 (09) :1278-1284
[16]  
LEFEBVRE AH, 1989, ATOMIZATION SPRAY, P79
[17]   Structure control of anisotropic and asymmetric polypropylene membrane prepared by thermally induced phase separation [J].
Matsuyama, H ;
Yuasa, M ;
Kitamura, Y ;
Teramoto, M ;
Lloyd, DR .
JOURNAL OF MEMBRANE SCIENCE, 2000, 179 (1-2) :91-100
[18]   Formation of hydrophilic microporous membranes via thermally induced phase separation [J].
Matsuyama, H ;
Berghmans, S ;
Lloyd, DR .
JOURNAL OF MEMBRANE SCIENCE, 1998, 142 (02) :213-224
[19]   Formation of anisotropic membranes via thermally induced phase separation [J].
Matsuyama, H ;
Berghmans, S ;
Lloyd, DR .
POLYMER, 1999, 40 (09) :2289-2301
[20]   Synergy between silica and polyoxyethylene surfactants in the formation of O/W emulsions [J].
Midmore, BR .
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, 1998, 145 (1-3) :133-143