Evaluation of the impact of abuse deterring agents on the physicochemical factors of tramadol-loaded tablet and the definition of new abuse deterrent index

In the design of abuse-deterrent formulations (ADFs), pharmaceutical strategies that do not modify the physical and chemical properties of opioid dosage forms should be investigated. Among these, four major drug abusing factors, including particle size by physical modification, swellability, dissolution rate, and solvent extraction, were mainly characterized for evaluating abuse deterrence of narcotics. Tramadol hydrochloride (TMD) was chosen as a model drug. In this study, the frequently used eight generally recognized as safe (GRAS)-listed pharmaceutical excipients, including polyvinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC 4,000, HPMC 100,000), xanthan gum (XG), cellulose acetate (CA), polyethylene oxide (PEO), carbomer 940 NF, and Compritol (R) 888 ATO, were selected as abuse deterring agents and used to prepare TMD-loaded tablet. A new abuse-deterrent index (ADI) for compressed TMD-loaded tablets was originally defined and considered as an index of drug abuse deterrence, based on the assumption that it was proportional to particle size and swellability but inversely proportional to dissolution and solvent extraction rates after assigning the categorized five scale scores (one to five) to the four experimental data. The resulting ADI of the selected eight abuse deterring agents in deionized water was given in decreasing order: HPMC 4000 > carbomer 940 > Compritol (R) 888 ATO > XG > PVA > HPMC 100,000 > PEO, and CA while in 40% hydro-alcoholic solution in the decreasing order: carbomer 940 > HPMC 4,000 approximately equal to or the image of XG > PVA > HPMC 100,000 > PEO > Compritol (R) 888 ATO > CA. Interestingly, the HPMC 4,000 and carbomer 940 showed the highest ADI and gave drug abuse deterrent potential. This study could provide a pharmaceutical strategy that utilizes a variety of abuse-deterring agents and resist to extraction solvents in designing drug abuse-deterrent formulations and establishing their standard guidelines for regulatory authorities.

Automated summary

In the design of abuse-deterrent formulations, pharmaceutical strategies that do not alter the physical and chemical properties of opioid dosage forms should be explored. This study investigated the abuse deterrence of narcotics by analyzing factors such as particle size, swellability, dissolution rate, and solvent extraction, using tramadol hydrochloride as a model drug. Eight commonly used pharmaceutical excipients were selected as abuse deterring agents to prepare TMD-loaded tablets, and a new abuse-deterrent index (ADI) was established to assess their effectiveness. The study found that HPMC 4000 and carbomer 940 exhibited the highest ADI values, indicating significant abuse deterrent potential.