Title: The effect of efflux bomb and the transmural potential difference in the permeation of azidothymidine across the small intestine of the rat
This study has been undertaken to investigate the influence of copolymers poly - L - co - D, L - lactic acid (PLDLA) 70:30 and Poly (ethylene glycol) - block - poly (propylene glycol) - block - poly (ethylene glycol) (P407) in the transmural transport of 3' - azido - 3' - deoxythymidine (azidothymidine (AZT), zidovudine). Based on anterior studies we use the proximal duodenum to evaluate, in vitro , the apparent intestinal permeability. The binary solid dispersion (SD) was prepared with, AZT, PLDLA, and P407. The supercritical antisolvent (SAS) technique was used to obtain the SD, whose was studied by scanning electron microscopy (SEM). The differential scanning calorimetry (DSC) showed that pure AZT had an endothermic peak corresponding to AZT melting point of 125,10 °C, which indicated its crystalline nature. In the SD the same melting point peak was observed. DSC thermogram indicated that thermal properties of P407 were altered in the SD, but the SD did not alter the thermal properties of AZT and PLDLA. Powder X - ray diffraction (X - RD) was used to detect, qualitatively, a material with long - range order. Sharper diffraction peaks indicate mor e crystalline AZT and P407. The diffraction spectrum of pure AZT and P407 confirmed their crystalline nature. Sharper diffraction peaks indicate more crystalline AZT and P407. The diffraction spectrum of pure AZT and P407 confirmed their crystalline nature . The X - RD spectrum of SD showed modifications in the crystalline lattice, the physical mixture (PM) X - RD spectrum showed the crystalline nature of AZT and P407. The Fourier Transform Infrared Spectroscopy (FTIR) analysis seems to indicate the absence of chemical interaction between copolymer and AZT, in binary solid dispersion and the presence of drug as a dispersion in the copolymer’s matrix. The SD modifies the crystalline state of AZT and P407 modify the morphology of PLDLA (30:70), and inhibit ed th e efflux pump. The transmural intestinal wall permeability can be evaluated, ex vivo, in a site - specific manner. Increase in intestinal permeability was observed in tan association of AZT with PLDL and P407 in a binary solid dispersion. SD can be used to altering abnormally the properties of drugs whose bioavailability is limited by the effect of the efflux pump. The supercritical fluid is an important technology to build particle design under strict quality assurance, environment - friendly, and scale - up w ith compliance to good manufacture products. Keywords: Binary Solid Dispersion, Supercritical Fluid Technology, Azidothymidine Bioavailability, HIV/AIDS, Transmural Permeability.