Abuse prevention by control release of opioids from micro to nano-structured silica xerogel delivery systems

摘要

Analgesics are a multi-billion dollar pharmaceutical industry in the developed world. Studies have proven OxyContin to be effective in treating pains associated with arthritis, lower back conditions, injuries, and cancer. Controlled-release Oxycodone became a significant source of drug abuse and death-related opioid abuse increased during the 21st century and opioid poisoning was a common cause of death compared to cocaine and heroin. Measures to curb its illicit use have been unsuccessful so far. Interest in developing abuse-proof alternative controlled-release methods was generated and remains a key issue in resolving the drug abuse problem. This study proposes that release concentrations, of opioid, not exceeding therapeutic target levels can be achieved in a nano-structurally optimized delivery material. Dextromethorphan (Dextro-inactive opioid, mol wt. similar to Oxycodone) was used. Micro-sized to nano-sized silica xerogels particles were synthesized using silica precursors (TMOS/ TEOS), via hydrolysis and condensation reactions coupled with varying drug loads and water-to-alkoxide ratios. Particles were immersed in PBS and concentration of released Dextro was measured spectrophotometrically. The effect of particle size on in vitro release of Dextro from xerogels demonstrated that mocro to nanoscale particles showed time-dependent release of Dextro. This demonstrates that a delivery material can be synthesized to achieve controlled release of therapeutically relevant doses. Data indicates that the principle of misuse resistance can be accomplished. Particle size reduction might not lead to any important increase in the release or a burst effect. It is highly probable, therefore to fabricate a nano-sized particle formulation of the drug to strengthen the misuse resistance.