title: 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 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.
authors: 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.
authors: Valquíria M H
authors: VM
authors: Yoshida
authors: Victor M
authors: VM
authors: Balcão
authors: Marta M D C
authors: MM
authors: Vila
authors: José M
authors: JM
authors: Oliveira Júnior
authors: Norberto
authors: N
authors: Aranha
authors: Marco V
authors: MV
authors: Chaud
authors: Maria P D
authors: MP
authors: Gremião
mesh_terms: D000818:Animals; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D019344:Lactic Acid / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000737:chemistry*; D015215:Zidovudine / Q000138:chemical synthesis* / Q000493:pharmacokinetics
chemical_list: D012997:Solvents; D019344:Lactic Acid; D015215:Zidovudine
keywords: everted rat intestinal sacs; gastrointestinal transit; oral absorption; permeability; poly(l-lactic acid); solid dispersion; supercritical antisolvent process; supercritical fluids; zidovudine