ABSTRACT
The aim of the present study was to develop a single unit, site-specific matrix tablets of aceclofenac allowing targeted drug release in the colon with a microbially degradable polymeric carrier, chondroitin suphate [CS] and to coat the optimized batches with a pH dependent polymeric. The tablets were prepared by wet granulation method using starch mucilage as a binding agent and HPMC K-100 as a swellable polymer. Chondroitin Sulphate and drug and physical mixture were characterized by Fourier transform infrared spectroscopy [FTIR] and differential scanning calorimetry [DSC]. The tablets were tested for their in-vitro dissolution characteristics in various simulated gastric fluids for their suitability as a colon-specific drug delivery system and also the tablets were evaluated for physicochemical properties, drug content, water percentage swelling and erosion characteristics. The dissolution data demonstrates that the 10% w/w increase in coating level of the pH dependent polymer [Eudragit L-100 and Eudragit S-100 in a ratio of 1: 4 prevented the drug release in the simulated gastric fluid [pH 1.2-SGF] and the simulated intestinal fluid [pH 7.4-SIF]. The dissolution rate of the tablet is dependent upon the concentration of Chondroitin sulphate in the simulated colonic fluid [SCF]. The rapid increase in release of aceclofenac in SCF was revealed as due to the degradation of the Chondroitin sulphate membrane by bacterial enzymes. The studies confirmed that, the designed system could be used potentially as a carrier for colon delivery of aceclofenac by regulating drug release in stomach and the small intestine
ABSTRACT
The objective of the present study is to develop a colon targeted drug delivery systems for Aceclofenac using xanthan gum as a carrier. In this study, multilayer coated system that is resistant to gastric and small intestinal conditions but can be easily degraded by colonic bacterial enzymes was designed to achieve effective colon delivery of Aceclofenac. The xanthan gum, the drug and the physical mixture were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). All the formulations were evaluated for hardness, drug content uniformity and other physical properties. Release aspects of Aceclofenac in simulated gastrointestinal fluid and colonic fluid with enzymes were investigated. From these results, Eudragit coated system exhibited gastric and small intestinal resistance to the release of Aceclofenac. The rapid increase in release of Aceclofenac in SCF was revealed as due to the degradation of the xanthan gum membrane by bacterial enzymes. The designed system could be used potentially as a carrier for colon delivery of Aceclofenac by regulating drug release in stomach and the small intestine.
O presente estudo teve como objetivo o desenvolvimento de sistema de liberação cólon-alvo de aceclofenaco empregando goma xantana. Nesse trabalho, o revestimento de múltiplas camadas com característica de resistência às condições do intestino delgado além de gastrorresistência oferece como vantagem a rápida degradação desse sistema por enzimas bacterianas colônicas. Dessa forma, o planejamento de tal sistema possibilitou a liberação específica do aceclofenaco no cólon. A goma xantana e o fármaco, além da mistura física desses dois componentes, foram caracterizados por espectroscopia no infravermelho com transformada de Fourier (FTIR) e calorimetria diferencial exploratória (DSC). Todas as formulações foram avaliadas no que se refere à dureza, à uniformidade de conteúdo do fármaco além de outras propriedades físicas. Os perfis de liberação do aceclofenaco no fluido gástrico simulado e fluido colônico simulado contendo enzimas foram investigados. Os resultados revelaram que o sistema revestido com Eudragit® exibiu resistência gástrica e intestinal à liberação de aceclofenaco. O rápido aumento na liberação de aceclofenaco no fluido colônico simulado foi atribuido à degradação da goma xantana por enzimas bacterianas. O sistema apresenta aplicação potencial no desenvolvimento de produtos para a liberação cólon-alvo de aceclofenaco.