TY - JOUR
T1 - Micronized powders of a poorly water soluble drug produced by a spray-freezing into liquid-emulsion process
AU - Rogers, True L.
AU - Overhoff, Kirk A.
AU - Shah, Parag
AU - Santiago, Patricia
AU - Yacaman, Miguel J.
AU - Johnston, Keith P.
AU - Williams, Robert O.
N1 - Funding Information:
The authors kindly acknowledge the financial support from The Dow Chemical Company. This material is based upon work supported by the STC Program of the National Science Foundation under Agreement No. CHE-9876674. Dr Raouf Ghaderi and Mr Jason M. Vaughn are appreciated for lending their expertise when the emulsion formulations were being designed. True L. Rogers is a continuing American Fellowship for Pharmaceutical Education (AFPE) Fellow from 2000–2002 and a 2001–2002 University Continuing Fellowship recipient.
PY - 2003/3
Y1 - 2003/3
N2 - 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 m2/g (SFL powder from solution) to 83.1 m2/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.
AB - 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 m2/g (SFL powder from solution) to 83.1 m2/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.
KW - Danazol
KW - Dissolution enhancement
KW - Emulsion
KW - Micronization
KW - Particle engineering
KW - Spray-freezing into liquid
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U2 - 10.1016/S0939-6411(02)00193-5
DO - 10.1016/S0939-6411(02)00193-5
M3 - Article
C2 - 12637092
AN - SCOPUS:0037333996
SN - 0939-6411
VL - 55
SP - 161
EP - 172
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
IS - 2
ER -