Date of Award
The objective of present study is to develop bilayer abuse-deterrent extended-release tablets (ADERTs) using various model drugs for opioids overdose crisis. Bilayer ADERTs using various model drugs were fabricated by direct compression; consists of extended-release drug layer and pH modifying layer. To develop extended-release layer, various hydrophilic polymers evaluated for their abuse deterrent potential. Based on significantly higher viscosity at 100RPM and lower syringe-ability data, it was found that HPMC K100M could be used as abuse deterrent polymer. Along HPMC K100M, various diluents were evaluated for their abuse deterrent potential. Tablet formulations prepared with various type of diluents using metformin HCl as model drug. Based on outcomes, MCC KG-1000 was selected as diluent to provide tablets with physical and/or chemical barrier. Bilayer ADERTs were developed to minimize multiple-unit oral abuse using three model drugs based on similar pKa values to that of opioids, i.e., propranolol HCl (pKa 9.45), quinidine sulfate (pKa 8.5), dipyridamole (pKa 6.59). Various alkalizing agents evaluated for their abuse deterrent potential. Bilayer ADERTs using propranolol HCl as model drug were fabricated. Based on outcomes, magnesium hydroxide was selected as alkalizing agent, since it raised pH of dissolving media near to pKa of all model drugs. Additional amount of magnesium hydroxide was incorporated in extended-release layer to minimize drug release in both FaSSGF and FaSSIF upon multiple-unit ingestion evaluated by in-vitro drug release study. Formulated bilayer ADERTs provided similar drug release profiles as compared to conventional extended-release tablets for single-unit ingestion. However, upon ingestion of multiple-unit bilayer ADERTs, fast-dissolving pH modifying layer increases pH in dissolving media, while extended-release layer increases micro-environmental pH within tablets for all model drugs tested. Retarding drug release owing to low solubility of basic drug at higher pH was observed. To minimize intravenous abuse, drug extraction study in various solvents were evaluated. Drug extraction was found to less than 2% for all the model drugs tested due to effect of alkalizing agent. Therefore, application of alkalizing agent has impact on pH-dependent solubility of drug like opioids and demonstrate its useful potential to be incorporated in bilayer ADERTs for opioids overdose crisis.
Soni, Ankit, "DEVELOPMENT AND CHARACTERIZATION OF BILAYER ABUSE DETERRENT EXTENDED RELEASE TABLET USING VARIOUS MODEL DRUGS FOR OPIOIDS OVERDOSE CRISIS" (2021). Theses and Dissertations. 190.