SOLID DISPERSION AS AN APPROACH FOR SOLUBILITY AND DISSOLUTION ENHANCEMENT OF IBUPROFEN AND PIROXICAM
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- NGN 3000
ABSTRACT
The aim of this study was to enhance the solubility and hence dissolution rate of two poorly soluble drugs: ibuprofen and piroxicam using Eudragit RS 100 and hydroxymethylpropylcellulose (HPMC) as carriers, by solid dispersion technique and to evaluate the effect of trona (sodium sesquicarbonate) on the dispersions . Solid dispersions of ibuprofen and piroxicam were prepared using HPMC or Eudragit RS 100 and their combinations by the solvent evaporation method. The prepared dispersions were characterized with respect to drug content, production yield, moisture sorption and desorption, Fourier Transform Infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC). The solubilities of the pure drug, solid dispersions and their physical mixtures were studied using standard method. In vitro drug release of ibuprofen and piroxicam from the solid dispersions was evaluated in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) without enzymes in a sequential fashion. Antiinflammatory effects of the solid dispersions were investigated in comparison to the pure drug using the egg albumin induced paw odema in rats. Stability studies at 75% relative humidity and room temperature (28oC) was carried out on the prepared solid dispersions. Results indicate that the solid dispersions with HPMC entrapped greater amount of drug in comparison to those with Eudragit RS 100. Moisture sorption studies indicate the amorphous state of drugs in the solid dispersions. Solubility studies revealed marked increase in solubility of drugs from solid dispersions when compared to pure drugs and physical mixtures. Solid dispersions of ibuprofen with HPMC containing 1:2 drug : polymer ratio had 8 fold increase in solubility when compared to pure drug . Solid dispersions of piroxicam with Eudragit and HPMC (ratio 0.1:1:1) gave a 3 fold increase in solubility when compared to the pure drug. Solid dispersion of the drugs with HPMC gave a faster drug release in simulated gastric fluid while Eudragit RS 100 based solid vii dispersions exhibited a delayed release of ibuprofen in the fluid. Solid dispersions of piroxicam incorporating trona showed enhanced solubility and dissolution when compared to dispersions without it, but trona was seen to decrease solubility and dissolution of ibuprofen. The FT-IR spectroscopic studies revealed that there was no chemical interaction between the drug and the polymers, while the DSC scans showed changes from crystalline to amorphous form of the drug. Solid dispersions were seen to have enhanced anti-inflammatory effect relative to the pure drug. Stability studies of these solid dispersions revealed that the formulations were stable.
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