RESUMO
The purpose of the current investigation was to formulate, assess, and optimize oral in situ gels of buspirone hydrochloride (BH) with the specific end goal of expanding the time the medication spends in the stomach, thereby ensuring an extended medication discharge. This would allow the use of a once-a-day dose of liquid BH formulations, which is ideal for the treatment of pediatric anxiety. In situ gels loaded with BH were prepared using various concentrations of sodium alginate (Na alg.), calcium chloride (CaCl2), and hydroxypropyl methylcellulose (HPMC K15M). The in situ gels exhibited the desired consistency, drug distribution, pH, ability to form gel, and prolonged drug release in vitro. The (33) full factorial design was utilized for the revealing of the ideal figures for the selected independent variables, Na alg. (X1), HPMC (X2), and CaCl2 (X3) based on measurements of the viscosity (Y1) and percentage drug release after 6 h (Y2). A pharmacokinetic study of the optimum formulation on rabbits was also performed. The formulation containing 2% of Na alg., 0.9% of HPMC-K15M, and 0.1125% of CaCl2 was selected as the ideal formulation, which gave the theoretical values of 269.2 cP and 44.9% for viscosity and percentage of drug released after 6 h, respectively. The pharmacokinetic study showed that the selected oral Na alg. in situ gel formulation displayed a prolonged release effect compared to BH solution and the marketed tablet (Buspar®), which was confirmed by the low Cmax and high Tmax values. The optimum oral Na alg. in situ gel showed a 1.5-fold increment in bioavailability compared with the drug solution.
RESUMO
Nasal nanovesicular gels of buspirone hydrochloride (BH) were prepared and characterized aiming for sustained delivery and enhancing bioavailability. Buspirone hydrochloride has low bioavailability of about 4% after oral administration due to first pass metabolism. Buspirone hydrochloride nanovesicles were formulated by thin film hydration method (TFH). The selected nanovesicular formulation was incorporated into two types of in situ gels (pH-induced and thermoreversible) using carbopol 974P and poloxamer 407 (P407), respectively, together with different mucoadhesive polymers. The in situ gels were examined for pH, gelling capability, viscosity, content uniformity, mucoadhesiveness, and in vitro drug release. The ex vivo permeation performance of the in situ gel formulations that showed the most sustained release was also assessed. The in vivo study was done by the determination of BH blood level in albino rabbits after nasal administration. Results revealed that nanovesicles prepared using Span 60 and cholesterol in a ratio of 80:20 showed the highest EE% (70.57 ± 1.00%). The ex vivo permeation data confirmed higher permeability figures for carbopol formulation in comparison to poloxamer formulations. The in vivo study data showed an increase of 3.26 times in BH bioavailability when formulated into the carbopol nanovesicular in situ gel relative to control (nasal drug solution).
