Development and in-vitro in-vivo characterization of in-situ gelling sustained-release nevirapine suspension
Nevirapine is a BCS class-II drug used in the treatment and prevention of HIV/AIDS, specifically HIV-1. This study was aimed to develop and evaluate a novel pH-responsive in-situ gelling sustained-release nevirapine pediatric suspension (SRNPS) for treatment and prevention of mother-to-child transmission of HIV. SRNPS can reduce the number of doses administered with subsequent improvement of patient compliance. Nevirapine anhydrous (NA) is unstable in the suspension formulation which leads to the formation of clusters. So here, initially, nevirapine hemihydrate (NH) was synthesized using NA.
Both NA and NH forms were later evaluated for differential scanning calorimetry (DSC), Fourier transforms infrared spectroscopy (FTIR) and Powder X-Ray diffraction (pXRD). Furthermore, for the preparation of SRNPS NH form was selected. The developed novel SRNPS was compared with marketed immediate-release nevirapine suspension (Viramune®). Further, both suspensions were evaluated for in-vitro drug release studies and in-vivo pharmacokinetic studies using a rat model. SRNPS has shown good in-situ gelling behavior and results have shown sustained drug release for 8 h.
The pharmacokinetic studies in rats also demonstrate an increase in the Cmax, Tmax and AUC for SRNPS compared to Viramune®. The observed Cmax for Viramune® and SRNPS is 0.548 ± 0.16 ng/mL and 0.670 ± 0.22 ng/mL respectively, observed Tmax is 3 ± 0.2 h and 6 ± 0.5 h respectively, while, AUC0-∞ for Viramune® and SRNPS is 26.61 ± 4.26 μg/ml*h and 59.23 ± 5.87 μg/ml*h respectively. The study thus supports the claim that development of SRNPS would minimize the dosing frequency along with sustained action.
Article information: Atul Garkal, Amelia Avachat, Development and in-vitro in-vivo characterization of in-situ gelling sustained-release nevirapine suspension, Journal of Drug Delivery Science and Technology, 2021. https://doi.org/10.1016/j.jddst.2021.102938.