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

• Published in: European journal of pharmaceutics and biopharmaceutics 2003-03, Vol.55 (2), p.161-172
• Main Authors: Rogers, True L., Overhoff, Kirk A., Shah, Parag, Santiago, Patricia, Yacaman, Miguel J., Johnston, Keith P., Williams, Robert O.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Danazol; Danazol - chemistry; Dissolution enhancement; Emulsion; Emulsions - chemistry; Excipients - chemistry; Freezing; General pharmacology; Medical sciences; Micronization; Microscopy, Electron; Particle engineering; Particle Size; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poloxamer - chemistry; Polyvinyl Alcohol - chemistry; Povidone - chemistry; Powders - chemistry; Solubility; Solvents - chemistry; Spray-freezing into liquid; Technology, Pharmaceutical; Water - chemistry; X-Ray Diffraction
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/S0939-6411(02)00193-5

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 (