A Promising Ternary Solid Dispersion of Aceclofenac Containing Tablet with Enhanced Dissolution, and Potentiated Anti-inflammatory Efficacy

Abstract

The major objective of the current study is to implement a plan to enhance the dissolution rate and oral bioavailability of a poorly water-soluble aceclofenac. The drug is classified according to the biopharmaceutical classification system as class II drug. Amorphous alkalinized aceclofenac solid dispersion was formulated as a ternary mixture. This mixture was prepared by introducing polymeric carriers [polyvinylpyrrolidone, Hydroxy propyl beta cyclodextrin or Polyethylene glycol] and an alkalizer (Na2CO3) by applying the solvent evaporation method. Optimum formulations were compressed into tablets that were subjected to in-vitro studies compared to the market product Bristaflam and free drug containing one. Finally, tablets were assessed for stability studies and carrageenan-induced rat paw edema treatment to evaluate potentiated anti-inflammatory efficacy.
 Results showed that optimum amorphous alkalinized aceclofenac solid dispersion formulations containing polyvinylpyrrolidone K30 or Hydroxy propyl beta cyclodextrin in 1:5 ratio have significant in-vitro dissolution improvement (>90% in 10 min) compared to untreated aceclofenac. Solid-state characterization emphasized the conversion of the crystalline drug into the amorphous form with no drug−polymers interactions. Stability and dissolution studies ensured that tablets containing amorphous alkalinized solid dispersions were stable with strikingly improving dissolution behavior compared to Bristaflam or free drug containing tablets. Moreover, regarding anti-inflammatory activity against carrageenan induced paw edema, and histopathological examination, we concluded that amorphous alkalinized solid dispersions containing tablets are a promising approach to enhance the dissolution rate and oral bioavailability and hence anti-inflammatory efficacy of aceclofenac.