Development of colon-specific mucoadhesive meloxicam microspheres for the treatment of CFA-induced arthritis in rats

Abstract

To fulfill the multi-task functions like enhanced solubility and bioavailability of poorly soluble drug, reduce dosing frequency, avoid acidic degradation, etc., hence uncoated meloxicam (MLX)-loaded colon-specific mucoadhesive microspheres (MLX-Na-AGP) were prepared by ionotropic gelation method (crosslinking technique) using sodium alginate and aloe vera gel powder as a drug release modifiers to achieve controlled and prolonged release pattern with maximum bioavailability and Calcium chloride(CaCl2) as crosslinking agent. A fixed drug concentration and various ratios blend of polymeric matrix were used in the preparation of microspheres. The combinative therapeutic effect of MLX with well-known anti-inflammatory medicinal value of AGP, while AGP is used as a carrier to the colon-specific microspheres for the treatment of “complete Freund’s adjuvant” (CFA) induced rheumatoid arthritis (RA) in Wistar rats. Various parameters and drug release potential were evaluated for developed microspheres, which showed satisfactory results. In FTIR studies, no substantial drug–polymer interactions were found. In vitro drug release of MLX-Na-AGP microspheres of all batches was carried out at progressive pH using different buffer solutions (0.1 N HCl pH 1.2 and pH 4.5, pH 6.8, pH 7.4 PBS buffers) at different time intervals for 24 h, and it was found that drug release followed zero-order kinetics with super case II transport drug release mechanism. All microspheres exhibited much slow drug release at acidic pH and that was increased progressively with increased pH and maximum drug release was found for all batches at pH 7.4 PBS at the end of 24 h. The prepared microspheres exhibited satisfactory micromeritic flow attributes which evaluated in terms of angle of repose (24.87 ± 0.45–32.05 ± 0.19°), bulk density (0.528 ± 0.007–0.731 ± 0.032 g/cc) and tapped density (0.684 ± 0.009–0.949 ± 0.037 g/cc), Compressibility index (10.62 ± 0.42%–23.03 ± 0.423%) and Hausner’s ratio (1.118 ± 0.005–1.299 ± 0.007). Mean particle size of different batch of formulations (F1–F14) was found in a range of 109.16 ± 0.96–1,025.12 ± 0.29 µm, respectively. Drug entrapment efficiency of the formulations was found in the range of 51.02 ± 0.19%–91.44 ± 0.1%. In pharmacokinetic study optimized formulation (F12) showed 2.29 times higher bioavailability over the free drug, and also showed significant results in pharmacodynamic studies and AGP in CFA-induced RA in animal model of male albino Wistar rats.