当前位置： SCI文献检索 > JOURNAL OF PHARMACEUTICAL SCIENCES期刊下所有文献 > Micronization of anti-inflammatory drugs for pulmonary delivery by a controlled crystallization process.

Micronization of anti-inflammatory drugs for pulmonary delivery by a controlled crystallization process.

Abstract：

:Jet-milling as the common way for micronization of drugs shows several disadvantages. Drug powder properties are decisive for pulmonary use because, besides a small particle size, a good deagglomeration behavior is required. In this study, several anti-inflammatory drugs [beclomethasone-17,21-dipropionate (BDP), betamethasone-17-valerate (BV), triamcinolone acetonide, ECU-R2, budesonide, and prednisolone] were micronized by controlled crystallization without any milling processes. First the drug is dissolved in an organic solvent (BDP/BV: 4%; ECU-R2: 1% in acetone) and precipitated by a solvent change method in the presence of a cellulose ether (hydroxypropylmethylcellulose) as stabilizing hydrocolloid. By rapid pouring the solution of hydroxypropylmethylcellulose in water (BDP/BV: 0.005%; ECU-R2: 0.025%) into the drug solution under stirring in a relationship (v/v) of 1:16 (BDP/BV), 1:4 (ECU-R2), the previously molecularly dispersed drug was associated to small particles and stabilized against crystal growth simultaneously. This dispersion was spray-dried, resulting in a drug powder with a uniform particle-size distribution and a drug load of up to 98% (BDP, BV). The mean particle size of the drug was lower than 5 microm in most cases and consequently in the respirable range. Whereas the fine particle fraction (<5 microm, measured without excipients and without an inhalation device) of jet-milled drugs is 9.5 (BDP) or 13.1 (ECU-R2), fine particle fractions of 25.6% (BDP) resp. 78.2% (ECU-R2) are obtained with the spray-dried powders. As the formation of the small crystals requires a rapid solvent change process, the affinity of the hydrocolloid, and a high difference between the solubility in the solvent and nonsolvent, the drug's partition coefficient limits the method as drugs which are more hydrophilic form larger particles.

journal_name

J Pharm Sci

journal_title

Journal of pharmaceutical sciences

authors

Rasenack N,Steckel H,Müller BW

doi

10.1002/jps.10274

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

35-44

issue

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)31156-X

journal_volume

pub_type

杂志文章

在线工具

Micronization of anti-inflammatory drugs for pulmonary delivery by a controlled crystallization process.