PROCESS-INDUCED CRYSTALLINITY CHANGES IN ALBUTEROL SULFATE AND ITS EFFECT ON POWDER PHYSICAL STABILITY

被引:189
作者
WARD, GH
SCHULTZ, RK
机构
[1] 3M Pharmaceuticals, St. Paul, Minnesota, 55144-1000
[2] Dura Pharmaceuticals, San Diego, California, 92121-4204
关键词
ABSORPTION; ALBUTEROL SULFATE; AMORPHOUS; CRYSTALLINITY; GLASS TRANSITION TEMPERATURE; MOISTURE; PHYSICAL STABILITY; WATER VAPOR;
D O I
10.1023/A:1016232230638
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Pharmaceutical powders are often milled to achieve the optimum particle size. These size reduction processes can introduce dislocations and/or defects onto particle surfaces affecting the overall crystallinity of the powder. If enough energy is imparted, amorphous regions on the particle surfaces may be produced. These amorphous regions have the propensity to absorb significant quantities of water. In this study the effect of sorbed water on the physical characteristics of albuterol sulfate is investigated. Physical properties of this compound are studied in both micronized and unmicronized states using scanning electron microscopy, differential scanning calorimetry, powder x-ray diffraction, solution microcalorimetry, laser diffraction particle size analysis and water vapor sorption analysis. Subtle differences in crystallinity induced by air jet micronization are detected by several analytical methods. Amorphous to crystalline conversions are observed, the kinetics of which are found to be both temperature and relative humidity dependent. These experiments show the dynamic nature of micronized albuterol sulfate and aid in the determination of the actual physical state of this pharmaceutical powder.
引用
收藏
页码:773 / 779
页数:7
相关论文
共 12 条
[1]  
Florence A., Salole E., Changes in crystallinity and solubility on comminution of digoxin and observations on spironolactone and oestradiol, J. Pharm. Pharmac., 28, pp. 637-642, (1976)
[2]  
Sekiguchi K., Shirotani K., Yuasa H., Suzuki E., Nakagawa. F., Size reducibility of sulfathiazole by heat transition and subsequent ball milling, Chem. Pharm. Bull., 28, pp. 3203-3209, (1980)
[3]  
Buckton G., Choularton A., Beezer A., Chatham S., The effect of the comminution technique on the surface energy of a powder, Int. J. Pharm., 47, pp. 121-128, (1988)
[4]  
Otsuka M., Kaneniwa N., Effect of grinding on the crystallinity and chemical stability in the solid state of cephalothin sodium, Int. J. Pharm., 62, pp. 65-73, (1990)
[5]  
Saleki-Gerhardt A., Ahlneck C., Zografi G., Assessment of disorder in crystalline solids, Int. J. Pharm., 101, pp. 237-247, (1994)
[6]  
Briggner L., Buckton G., Bystrom K., Darcy P., The use of microcalorimetry in the study of changes in crystallinity induced during the processing of powders, Int. J. Pharm., 105, pp. 125-135, (1994)
[7]  
Zografi G., States of water associated with solids, Drug Dev. Indust. Pharm., 14, pp. 1905-1926, (1988)
[8]  
Ahlneck C., Zografi G., The molecular basis of moisture effects on the physical and chemical stability of drugs in the solid state, Int. J. Pharm., 62, pp. 87-95, (1990)
[9]  
Oksanen C., Zografi G., The relationship between the glass transition temperature and water vapor absorption by poly(vinylpyrrolidone), Pharm. Res., 7, (1990)
[10]  
Hancock B., Zografi G., The relationship between the glass transition temperature and the water content of amorphous pharmaceutical solids, Pharm. Res., 11, pp. 471-477, (1994)