Zidovudine-poly (L-lactic acid) solid dispersions with improved intestinal permeability prepared by supercritical antisolvent process
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Data
2015-05-01
Autores
Yoshida, Valquiria M. H. [UNESP]
Balcao, Victor M.
Vila, Marta M. D. C.
Oliveira Junior, Jose M.
Aranha, Norberto
Chaud, Marco V.
Gremiao, Maria P. D. [UNESP]
Título da Revista
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Título de Volume
Editor
Wiley-Blackwell
Resumo
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
Descrição
Palavras-chave
Supercritical antisolvent process, Supercritical fluids, Zidovudine, Poly (l-lactic acid), Solid dispersion, Oral absorption, Gastrointestinal transit, Everted rat intestinal sacs, Permeability
Como citar
Journal Of Pharmaceutical Sciences. Hoboken: Wiley-blackwell, v. 104, n. 5, p. 1691-1700, 2015.