Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10162092 | Journal of Pharmaceutical Sciences | 2015 | 10 Pages |
Abstract
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 32 factorial design was used, having as independent variables the ratio 3â²-azido-2â²3â²- 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 (~Â 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.
Keywords
Related Topics
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
ValquÃria M.H. Yoshida, Victor M. Balcão, Marta M.D.C. Vila, José M. Oliveira Júnior, Norberto Aranha, Marco V. Chaud, Maria P.D. Gremião,