Category: Formulation and Quality
Purpose: This study was conducted to develop and optimize a poly(acrylic acid)-based formulation that resists opioid drug extraction for intravenous abuse by forming hydrogels in aqueous solutions. The gel strength, representing the deterrence capacity, of different poly(acrylic acid)-based compositions was evaluated, and the deterrence stability of the optimized composition was further investigated after 3 months at ambient storage conditions.
Methods: Poly(acrylic acid)-based formulations containing 50, 100, 125, 150, and 200 mg of the polymer, 25 mg dextromethorphan HBr, and an alkalizing agent were vortex mixed with 10 mL of different extracting solvents including water, pH3 solution, 40% ethanol, normal saline, and 0.1N HCl. A quantitative method was developed to measure the gel strength of the samples using a texture analyzer (Brookfield, CT3 - 4500). A resistance sensitive probe allowed to travel into the gels up to 10 mm at a rate of 1 mm/sec. The gel resistance (mN) to the probe penetration was measured using a TexturePro software, indicating the extraction resistance capacity. Based on the gel strength studies, the optimized formulation was established and further investigated for the kinetics of the gel formation after 1, 5, 10, and 20 min. in normal saline, where the gel formation was delayed. The rate at which the probe was travelling to the gel was set at 0.5 mm/sec. and the resistance exerted by the gel was plotted against the distance travelled by the probe to find out the equilibrium gelation. Furthermore, the gel strength of the optimized formulation was determined over a 3-month storage in a high-density polyethylene (HDPE) container at 25 ± 2ºC and 60 ± 5% RH.
Results: A tablet formulation (500 mg) with a minimum 150 mg of poly(acrylic acid) formed an effective gel ( >200 mN) in all extraction media, while maintaining its liquid state in 0.1N HCl. Formulations containing 150-200 mg of the deterring polymer formed a noticeable gel in saline following a lag period of about 5 minutes. The gel strength data after 10 and 20 minutes were statistically similar. The gel strength values of the optimized formulation showed a maximum of 14.5 mN difference over the 3 months storage period, and the stability data were not statistically different from that of the control.
Conclusion: Poly (acrylic acid)-based formulations can prevent drug extraction in different solvents by forming strong gels at reasonable time. Moreover, the formulation remains stable and retains its gel formation ability upon storage at ambient temperature and humidity conditions.