Zidovudine-poly(l-lactic acid) solid dispersions with improved intestinal permeability prepared by supercritical antisolvent process

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 3-azido-23-dideoxythymidine (AZT)PLLA and temperature/pressure conditions, as dependent variables the process yield and particle macroscopic morphology. AZTPLLA 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 (AZTPLLA) ratio, resulted in a 91.54% yield, with 40% AZT content. Intestinal permeability studies using the AZTPLLA 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.