Effect of alkalizing agent on abuse deterrent potential of multiple-unit ingestion of bilayer abuse-deterrent extended-release tablets using propranolol as model drug for opioids overdose crisis.

The objective of present study is to develop bilayer abuse-deterrent extended-release tablets (ADERTs) using propranolol HCl as model drug for opioids overdose crisis. Bilayer ADERTs were fabricated by direct compression and formulated with polymer matrix in extended-release drug layer coupled with alkalizing and aversive agents in fast-disintegrating pH modifying layer. Various alkalizing agents, like magnesium hydroxide, aluminum hydroxide, calcium carbonate, and calcium hydroxide, were evaluated for their abuse-deterrent potential via in-vitro drug release and extraction studies. Based on the outcomes, magnesium hydroxide was selected as an alkalizing agent, since it raised the pH of dissolving media near to pKa of the drug studied in this investigation. The formulated bilayer ADERTs with magnesium hydroxide provided similar drug release profiles as compared to conventional extended-release tablets for single-unit ingestion. However, upon ingestion of multiple-unit bilayer ADERTs, the fast-disintegrating pH modifying layer increases pH of dissolving media, while extended-release layer increases micro-environmental pH within tablets. Retarding drug release owing to low solubility of basic drug at higher pH was observed. Therefore, the 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.