Abuse of opioid drug products is a national health crisis in the US. To deter abuse, a number of drug products with abuse-deterrent (AD) properties have been approved by the US Food and Drug Administration (FDA). For abuse deterrence, it is critical to maintain the AD properties during the product shelf life. However, no information on the stability of AD properties during product shelf life is publicly available. In this study, stability of AD properties of surrogate AD formulation (ADF) of opioid active pharmaceutical ingredients (APIs) were studied. Surrogate extended release (ER) AD tablets were prepared by direct compression using Diltiazem HCl (model drug), polyethylene oxide (PEO WSR 301) polymer and magnesium stearate followed by curing at 70 °C for 30 mins. The stability studies were conducted at 25 °C/60 % RH and 40 °C/75 % RH storage conditions for 12 months (M) and 6 months (M), respectively. In vitro characterization and evaluation of AD properties of tablets were performed. As anticipated, the curing process increased the crushing strength of the tablets. However, the tablets could still be manipulated and compromised leading to an enhancement in the amount of drug extracted in solvents (e.g., water, alcohol), regardless of extraction temperature as well as tablet storage condition and time. Furthermore, the granule particle size as well as viscosity in water of manipulated samples were found to be lower for tablets stored at 25 °C/60 % RH or 40 °C/75 % RH for 12 M or 3 M/6M, respectively. The changes in AD properties eased the syringeability of hydrated samples and ultimately led to the withdrawal of higher amounts of drug into the syringe, thereby, impacting the abuse deterrence potential of the formulation by an IV route. These data demonstrated that the stability of AD properties (i.e., granule particle size, viscosity and syringeability-injectability) of PEO-based tablets was dependent on the storage condition. In conclusion, the design of AD formulation and setting of product quality profile should take into consideration the stability of AD properties during the product shelf life.
Published by Elsevier B.V.