期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 104, 期 5, 页码 1691-1700出版社
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.24377
关键词
supercritical antisolvent process; supercritical fluids; zidovudine; poly(l-lactic acid); solid dispersion; oral absorption; gastrointestinal transit; everted rat intestinal sacs; permeability
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2013-19300-4, 2012/01333-0, 2011/21219-5]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (PROSUP/CAPES)
- Finep Inovacao e Pesquisa (Finep, Brazil) [01.13.0286.00]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [12/01333-0] Funding Source: FAPESP
A supercritical antisolvent (SAS) process for obtaining zidovudine-poly(l-lactic acid) (PLLA) solid dispersions (SDs) was used to attain a better intestinal permeation of this drug. A 3(2) factorial design was used, having as independent variables the ratio 3-azido-23-dideoxythymidine (AZT)-PLLA and temperature/pressure conditions, as dependent variables the process yield and particle macroscopic morphology. AZT-PLLA production batches were carried out by the SAS process, and the resulting products evaluated via scanning electron microscope, X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared analyses. From the nine possible combinations of tests performed experimentally, only one combination did not produced a solid. The L3 batch of SD, produced with 1:2 (AZT-PLLA) ratio, resulted in a 91.54% yield, with 40% AZT content. Intestinal permeability studies using the AZT-PLLA from L3 batch led to an AZT permeability of approximately 9.87%, which was higher than that of pure AZT (approximate to 3.84%). AZT remained in crystalline form, whereas PLLA remained in semicrystalline form. AZT release is controlled by a diffusion mechanism. It has been demonstrated that it is possible to use PLLA carrier and SAS process to obtain SD, in a single step. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1691-1700, 2015
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