Polymeric coating and pharmacokinetic of chitosan granules containing ddI incorporated in microparticles / Revestimento polimerico e farmacocinetica de granulos gastrorresistentes contendo didanosina incorporada em microparticulas de quitosana

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

This work studied the production and pharmacokinetic of a new pharmaceutical formulation of the didanosine (ddI) drug ,composed by chitosan granules containing ddI incorporated in microparticles, for oral administration in the AIDS therapy. The advantages of this new pharmaceutical formulation compared to the conventional one are: to assure ddI stability in gastrointestinal medium, to produce adhesion to intestinal membrane, enhancing absorption through the increasing of permeation and controlled release and to facilitate the handling and deglutition especially to elderly and children. The approach included the following aspects: optimization of the ddI amount in the chitosan microparticles previously developed by Silva, 2006; production of granules in fluidized bed and by extrusion/spheronization; polymeric gastroresistent coating in fluidized bed and acquiring of the plasmatic pharmacokinetic profiles in dogs through oral administration of the produced granules. The optimization of ddI amount in granules was carried out through modifications on the fluid-dynamic conditions of the process for production of the microparticles. The production and coating were carried out in fluidized bed, evaluating the variables of the process. A polymeric suspension of Kollicoat® MAE 100 P for coated enteric coating was used, because the ddI suffers desacetilation and losses its pharmacological efficacy when exposed to the gastric pH. The plasmatic pharmacokinetic profiles in dogs were analyzed by non-compartimental models. The experimental results shown that the encapsulation of ddI in microparticles was increased 13.3% compared to the previous formulation developed by Silva 2006, when modified fluid-dynamic conditions were introduced in the production process. The enteric coating of the granules was suitable as evaluated in vitro according to pharmacopeia. The analytical CLAE methodology associated to extraction in solid phase was adequated for the quantification of ddI. This methodology was validated to determine simultaneously ddI and ACL (internal standard) in samples of dog s plasma. The kinetic profiles shown that the new formulation is statistically different of the formulations distributed by SUS due to its controlled delivery along 36 hours. These results contribute for development new pharmaceutical form for oral administration. That possibility controlled liberation, requiring lower administration frequency, promoting treatment adhesion in a lot of diseases.

ASSUNTO(S)

granule agentes antivirais microparticle aids (disease) tecnologia de liberação controlada chitosan didanosine quitosana microencapsulação aids (doença)

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