Yoshida Valquíria M H, Balcão Victor M, Vila Marta M D C, Oliveira Júnior José M, Aranha Norberto, Chaud Marco V, Gremião Maria P D
Laboratory of Biomaterials and Nanotechnology of the University of Sorocaba, University of Sorocaba, Sorocaba, São Paulo, Brazil; School of Pharmaceutical Sciences, São Paulo State University-UNESP, Araraquara, São Paulo, Brazil.
J Pharm Sci. 2015 May;104(5):1691-700. doi: 10.1002/jps.24377. Epub 2015 Feb 10.
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-2'3'-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 (∼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.
采用超临界抗溶剂（SAS）工艺制备齐多夫定-聚（L-乳酸）（PLLA）固体分散体（SDs），以提高该药物的肠道渗透性。采用3（2）析因设计，将3'-叠氮-2'，3'-二脱氧胸苷（AZT）与PLLA的比例以及温度/压力条件作为自变量，将工艺产率和颗粒宏观形态作为因变量。通过SAS工艺制备AZT-PLLA生产批次，并通过扫描电子显微镜、X射线衍射、差示扫描量热法和傅里叶变换红外分析对所得产品进行评估。在实验进行的九种可能的测试组合中，只有一种组合未产生固体。以1:2（AZT-PLLA）比例生产的L3批次SD的产率为91.54%，AZT含量为40%。使用L3批次的AZT-PLLA进行的肠道渗透性研究表明，AZT的渗透率约为9.87%，高于纯AZT（约3.84%）。AZT保持结晶形式，而PLLA保持半结晶形式。AZT的释放受扩散机制控制。已证明可以使用PLLA载体和SAS工艺一步获得SD。
