Ease of Manipulating Dosage Forms for Nasal Insufflation

Objective. The main objective of this study was to evaluate the degree to which different manipulation methods can reduce the size of a standard tablet to particles suitable for nasal insufflation. Background. Prescription pain medications are among the most commonly-abused drugs and frequently manipulated for abuse via the nasal route. Manipulating the dosage forms involve chewing, crushing, breaking, milling, or grinding to accelerate drug release via snorting, oral ingestion, injection, or smoking. Using common methods employed by abusers to reduce particle size, the ability of each methods to produce small particles suitable for aerosolization (~ 250 microns) was determined. Methods. Tablets consisting of 80 mg acetaminophen and 320 mg high molecular weight polyethylene oxide (Polyox® WSR coagulant) were prepared on a single station Carver press at 2000 pounds of force. Tablets were then manipulated by various methods including two manual and four mechanical methods for one minute (n=3). The resultant product was then separated by particle size above and below 250 microns using sieve analysis. Results. Each method was highly capable of producing light particles from tablets with a measured breaking force of 124.2 N. The percentage of particles ~ 250 microns generated by each method was 20.3 ± 0.7, 45.5 ± 3.2, 43.5 ± 1.6, 20.0 ± 0.7 and 33.3 ± 0.4 for pill crusher, mortar-pestle, ball mill, high shear grinder and domestic blender, respectively. Conclusion. Standard tablets offer minimal resistance to particle size reduction. Tablets formulated with abusable medications should have enhanced mechanical properties to deter abuse. Grants. NSU grants # 335357 and 335829