Development of QbD-based mupirocin-beta-cyclodextrin complex loaded thermosensitive in-situ gel for wound healing in mice

Mupirocin is a potent antibacterial drug used topically in different dosage forms. However, it has a limitation of low aqueous solubility. Therefore, the purpose of this study was to prepare a complex of mupirocin (MUP) with beta-cyclodextrin (beta-CD) to enhance the solubility and develop a thermosensitive in-situ gel for improved patient compliance. Mupirocin-beta-cyclodextrin (MUP-beta-CD) complex was prepared, and the formation of the inclusion complex was confirmed by nuclear magnetic resonance spectroscopy (NMR), fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), x-ray diffractometry (XRD) and scanning electron microscopy (SEM). The thermosensitive in-situ gel was optimized by response surface methodology (central composite design). The formulation was prepared by the cold method using pluronic F-127 and pluronic F-68, and 2% w/v mupirocin and characterized for gelation temperature (32 +/- 0.5 degrees C), pH (5.35 +/- 0.2), viscosity (9970 +/- 31.75 cps at 50 rpm), in-vitro drug release (94.81 +/- 1.38%), drug content (96.05 +/- 1.24%) and texture parameters. It showed a broader zone of inhibition against Staphylococcus aureus (26 +/- 0.8 mm) and Staphylococcus epidermidis (6 +/- 1.36 mm). The excisional-wound model in mice showed a remarkable wound contraction (99.9 +/- 0.22%), epithelialization period (13.5 +/- 0.5 days), and hydroxyproline content (36.10 +/- 4.05 mg/gm skin tissue). In conclusion, a thermosensitive mupirocin-beta-cyclodextrin complex in-situ gel was prepared successfully, which exhibited improved antibacterial and wound-healing properties.