Formulation and enhancement of dissolution rate of poorly aqueous soluble drug Aceclofenac by solid dispersion method: In vitro study

Abstract

Solid dispersion technique was successfully used to enhance the dissolution of poorly aqueous soluble drugs aceclofenac. Four carriers Hydroxyl propyl methylcellulose (HPMC), polyvinyl alcohol (PVA), Mannitol and Dextrose in two ratios (1:2, 1:3 w/w) were used to prepare solid dispersion. Eight different formulations were designed by the varying carrier and the drug: Carrier ratio and solvent wetting method was used for preparing solid dispersion. Acquired formulations were used for various micrometric and in vitro drug release studies. The solubility of aceclofenac in distilled water was 0.0753±0.021 mg/ml. The study shows that aceclofenac solubility is pH-dependent where the solubility observed was greater in phosphate buffer (pH 7.4) at 5.76±1.23 mg/ml compared to acid buffer (0.1 N HCl) at 0.0214±0.012 mg/ml. The percentage yield measured in F5 was higher at 85.18±6.02% and lower at 70.43±5.028% in F1. Micrometric study suggest that the Carr's index and Hausner's ratio value was smallest for F4 with 5.018±0.0025 and 1.06±0.0025 respectively, indicating an excellent flow property and greatest for F6 with 15.35±0.0022 and 1.18±0.0022, indicating relatively poor flow. The angle of repose value was lower for F5 with 20.77±2.9º and higher for F2 with 30.77±2.1º. Both acid buffer (pH 1.2) and phosphate buffer (pH 7.4) were undertaken for in vitro drug release study of pure drug aceclofenac and eight separate formulations. The in vitro drug release after 180 min for aceclofenac in acidic buffer (pH 1.2) was 3.89±0.41% and was highest in F8 with 54.73±4.60 % and lowest in F5 with 31.75±3.10 %. Drug release was significant compared to pure drug aceclofenac (p<0.05) in acidic buffer. Similarly, in vitro drug release after 180 min for aceclofenac in phosphate buffer (pH 7.4) was 23.79±2.20% and was highest in F8 with 76.65±6.50% and lowest in F5 with 64.09±5.70%. The data was analyzed by Dunnett's multiple comparison tests while statistical significance was predefined at p<0.05.

Sugars and Polyols of Natural Origin as Carriers for Solubility and Dissolution Enhancement

“…The characterization of SDs using techniques like DSC has revealed a decrease in the melting point [81] and a broadening or disappearance of the melting peak [82,83], which are indicative of the reduced particle size or amorphization of the drug. Along with the positive effect on solubility and the dissolution rate, mannitol-based SDs have been reported to enhance powder flow properties [84,85] and drug permeation efficacy [81]. It is worth noting that, while none of these studies have reported the formation of a completely amorphous system, they have often observed the drug becoming amorphous while mannitol remained in the crystalline state [44,81,86,87].…”

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

“…AFC has a pH dependent solubility which increased in an alkaline medium more than acidic pH [30,50,51]. The results indicated that AFC had the greatest solubility in 1% Na 2 Co 3 solution (60.515±2.12 mg/ml), so it was chosen as an alkalizing agent for AA-AFC-SD preparations.…”