Zidovudine-Poly(L-Lactic Acid) Solid Dispersions with Improved Intestinal Permeability Prepared by Supercritical Antisolvent Process

Author(s)

Yoshida, Valquiria M. H. ^{[1, 2]} ; Balcao, Victor M. ^{[2, 3]} ; Vila, Marta M. D. C. ^[2] ; Oliveira Junior, Jose M. ^[4] ; Aranha, Norberto ^[4] ; Chaud, Marco V. ^[2] ; Gremiao, Maria P. D. ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Sao Paulo - Brazil

^[2] Univ Sorocaba, Lab Biomat & Nanotechnol, Sao Paulo - Brazil

^[3] Univ Minho, Ctr Biol Engn, Braga - Portugal

^[4] Univ Sorocaba, Lab Appl Nucl Phys, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Pharmaceutical Sciences; v. 104, n. 5, p. 1691-1700, MAY 2015.
• Web of Science Citations: 6

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 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 (AU)

• FAPESP's process: 11/21219-5 - Preparation, in vitro characterization and in vivo evaluation of mucoadhesive polymer films in the prevention and treatment of acute oral mucositis induced by chemotherapy and radiotherapy
• Grantee: Marco Vinícius Chaud
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/01333-0 - Development and evaluation of controlled release systems obtained by supercritical fluid technology
• Grantee: Marco Vinícius Chaud
• Support Opportunities: Regular Research Grants