*Corresponding Author: Dr. Amul Mishra, Associate Professor & Head of Pharmaceutics, Bhupal Nobles' Institute of Pharmaceutical Sciences, Bhupal Nobles' University, Udaipur, Rajasthan, INDIA. Email: amulnmishra@gmail.com | Phone: +91-9414738107
Objective: To characterize the in vitro abuse-deterrent performance of a QbD-optimized extended-release (ER) matrix tablet containing metformin HCl as a non-opioid model drug, focusing on crushing behaviour, particle size distribution, extraction, syringeability/injectability and alcohol-induced dose dumping.
Methods: The abuse-deterrent formulation (ADF) of Metformin HCl was optimized using mixture design by using hydrophilic polymer Kollidon SR, HPMC K4M, Carbopol 971P and Polyplasdone XL screened in previous study based on drug release in alcoholic media. The optimized ADF (F1) was assessed under category-1 in vitro tampering tests consistent with regulatory recommendations. The ADF tablets were crushed using a pestle–mortar and a domestic coffee grinder; particle size distribution was determined by sieve analysis (500, 250 and 180 µm). Extraction studies employed small volumes (5 mL) of common household solvents (water and ethanol) to quantify drug recovery and potential for solution abuse. Syringeability and injectability were evaluated by attempting to aspirate and expel manipulated samples through standard hypodermic needles. In vitro dissolution in 0.1 N HCl and 0.1 N HCl + 40% v/v ethanol was performed to assess alcohol-induced dose dumping and to compare initial and 3-month stability samples.
Results: The drug release from optimized formulation (F1) in alcoholic media (40% ethanol) is <10% more than drug release in non-alcoholic media (0.1N HCl). Particle size of crushed tablets of F1 is more than 500 µm for more than 30-50% of the mass, even the high content of hydrophilic polymers promoted gelation upon contact with moisture which makes F1 formulation not attractive to abusers. Extraction studies in 5 mL of water or ethanol showed restricted drug recovery (4–6% at 5 minutes, 10–14% at 30 minutes), consistent with high viscosity and gel formation in small volumes, suggesting a low risk of rapid dose extraction for injection. Syringeability and injectability tests demonstrated poor ability to draw and eject manipulated formulations through standard needles due to gel formation and particle obstruction. Stability samples showed comparable release and tamper-resistance behaviours after three months at 40°C/75% RH.
Conclusion: The optimized ADF (F1) exhibits multiple complementary in vitro abuse-deterrent properties, including resistance to size reduction, limited extractability in small solvent volumes, poor syringeability/injectability and minimal alcohol-induced dose dumping. These results support the suitability of the QbD-engineered polymeric matrix as a candidate platform for abuse-deterrent ER formulations of high-risk opiates.
Keywords: Abuse-Deterrent Formulation, Crushing Resistance, Extraction, Syringeability, Injectability, Alcohol-Induced Dose Dumping, In Vitro Testing, Metformin, QbD.
How to cite this article: Mishra A, Kumar V. In vitro abuse-deterrent performance of a QbD-optimized metformin HCl extended-release matrix tablet: resistance to crushing, extraction, syringeability and alcohol-induced dose dumping. Int J Drug Deliv Technol. 2026;16(3s): 734-755; DOI: 10.25258/ijddt.16.3s.91
Source of support: Nil.
Conflict of interest: None