ETHANOL DOSE DUMPING AND RHEOLOGY OF ABUSE-DETERRENT EXTRACTS

Objective. The goal of this research was to determine the ability of three pharmaceutical polymers (hydroxypropylcellulose, polyethylene oxide, Carbopol 940) to maintain a high viscosity in hydroalcoholic solutions under different rates of mixing. Background. Abuse-deterrent formulations often contain materials which form a gel or highly viscous liquid when in contact with water or hydroalcoholic solutions. Increase in viscosity and gelling is done to prevent the drug from rapidly being released (dose dumping) and also prevent the product from being dissolved and drawn-up into a syringe. Evaluation of polymers for this purpose have not been extensively tested over a range of alcoholic concentrations and mixing (shear rates). Methods. Continuous shear rheometry was performed using a Wells-Brookfield cone-and-plate rheometer. Measurements were taken with an attached cone of radius 2.4 cm, and cone angle of 0.8 at a constant temperature. Polymer solutions (2% w/v) were subjected to increasing shear rates ranging from 37.5 to 1425 sec-1 to generate individual rheograms. Results. Carbopol 940 and polyethylene oxide displayed higher viscosities at shear rates close to that of slow mixing and stirring (10-100 sec-1) but displayed significant loss of viscosity at higher shear rates. Comparatively, hydroxypropylcellulose displayed extremely low viscosities over all shear rates. However, all solutions showed higher viscosities in hydroalcoholic solutions (5-20% v/v) than water. Conclusion. The effectiveness of pharmaceutical polymers for abuse deterrence in hydroalcoholic solutions appears to be dependent on the ethanol concentration and shear rate. Grants. Funding for this project was provided by NSU's grants # 335867 and 335489