RESUMEN
Long-acting injectable (LAI) formulations provide sustained drug release over an extended period ranging from weeks to several months to improve efficacy, safety, and compliance. Nevertheless, many challenges arise in the development and regulatory assessment of LAI drug products due to a limited understanding of the tissue response to injected particles (e.g., inflammation) impacting in vivo performance. Mechanism-based in silico methods may support the understanding of LAI-physiology interactions. The objectives of this study were as follows: (1) to use a mechanistic modeling approach to delineate the in vivo performance of DepoSubQ Provera® and formulation variants in preclinical species; (2) to predict human exposure based on the knowledge gained from the animal model. The PBPK model evaluated different elements involved in LAI administration and showed that (1) the effective in vivo particle size is potentially larger than the measured in vitro particle size, which could be due to particle aggregation at the injection site, and (2) local inflammation is a key process at the injection site that results in a transient increase in depot volume. This work highlights how a mechanistic modeling approach can identify critical physiological events and product attributes that may affect the in vivo performance of LAIs.
RESUMEN
The purpose of the present study was to investigate the analgesic activity of ethanol extract of leaf, stem, and their different fractions i.e. pet-ether, dichloromethane, and methanol fraction of Swertia chirata (Family-Gentianaceae) on Swiss albino mice. Acetic acid induced writhing in mice was used as the process to evaluate the analgesic activity. The ethanol extract of leaf and stem of Swertia chirata showed moderate inhibition (p<0.001) of writhing. Among different fractions pet-ether fraction showed significant inhibition (p<0.0001) of writhing where as methanol fraction showed moderate inhibition (p<0.003) of writhing as well. The inhibition of writhing was calculated in respective to control (vehicle). The test samples were administered at a dose of 200 mg/kg body weight of experimental animals where diclofenac sodium at a dose of 25 mg/kg body weight was used as standard drug in this study.