New immediate release formulation for deterring abuse of methadone.

CONTEXT: Drug abusers are known to take a dosage form containing an opioid analgesic and crush, shear, grind, chew, or dissolve it in water or in alcohol, in order to extract the opioid component. OBJECTIVE: Develop an anti abuse immediate release formulation using methadone as model drug. MATERIALS AND METHODS: Tablets combining methadone and alkalizing agents were manufactured. A methadone assay was used to determine extraction efficiency from tablets in aqueous and alcohol solvents. In vitro dissolution testing was used to determine drug release in different media. RESULTS AND DISCUSSIONS: Meglumine-based formulations prevented extraction of 70 to 100% of methadone from tablets. Addition of this alkalizing agent caused methadone to precipitate out of a solution along with other ingredients and be retained on standard filters. Meglumine-containing and control tablets showed similar dissolution profiles in acidic media, suggesting adequate solubilisation of the drug early in the gastrointestinal tract. Finally, stability upon storage of the formulations for 6 months at 25°C/60%RH and 40°C/75%RH was confirmed. CONCLUSION: Incorporation of an alkalizing agent into methadone tablets significantly reduced the preparation of a methadone solution for intravenous administration and abuse, while allowing the formulation to release methadone in gastric media and provide desired pharmacological effect.

Polymorphic properties of micronized carbamazepine produced by RESS.

Carbamazepine microparticles were produced by the rapid expansion of supercritical carbon dioxide solutions (RESS) method. The characteristics of the resulting particles were studied by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and image analysis. X-ray diffractograms and SEM photomicrographs revealed that the crystalline nature of the produced carbamazepine microparticles depended on operating pressure and temperature conditions. Different polymorphs were obtained under various operating conditions. Under certain temperature (below 40 degrees C) and pressure (below 240 bar) conditions, it was possible to form primarily the carbamazepine polymorph stipulated by US Pharmacopeia. A significant reduction was observed in the particle size and size distribution range of carbamazepine produced by RESS. The processed particles had a mean diameter smaller than 3 microm and a size distribution range between 0.5 and 2.5 microm compared to unprocessed starting material with a mean diameter of approximately 85 microm and a size distribution range between 15 and 336 microm. Thus, this study demonstrates that the polymorphic characteristics of carbamazepine microparticles produced by the RESS method can be controlled by varying operating pressure and temperature parameters.