Hot tabletting of slow-release tramadol hydrochloride microcapsules with cores obtained via compaction.

BACKGROUND

Coating, as a processing technique, applied to active pharmaceutical ingredient (API) crystals or particles (carriers) with an appropriate polymer allows to obtain a modified-release pharmaceutical dosage form. Such carriers can be the basic ingredient of a multi-unit dosage form. Additionally, coated API crystals (microcapsules) can provide an alternative to spherical granulate (pellets) as the main and most commonly used component of multi-unit dosage forms. Coating individual API crystals is a complicated process because of the crystals having insufficient size (below 100 microm), irregular shape, low mechanical durability and the fact that API crystals dissolve upon contact with the coating mixture, and other factors.

METHOD

Compaction process was used to eliminate these inconveniences allowing us to obtain tramadol hydrochloride (TH) microcapsule cores in the size range of 212-500 microm. The coating of the cores was successfully conducted using a fluidized-bed coating technique with four different polymers that allowed us to attain slow release of TH. Then, the microcapsules were subjected to a hot tabletting process conducted by applying a low compression force of about 1 kN at 56 degrees C. Semi-liquid granules containing melted PEG 3000 combined with TH microcapsules were compressed. A tablet matrix of good physical parameters was created when its temperature decreased to room temperature. In the proposed hot tabletting method, PEG 3000 included in the granulate provided the tableted microcapsules sufficient protection against rupture.

RESULTS

The compaction process allowed us to eliminate unwanted physical API properties, which could otherwise have an adverse effect on the fluidized-bed coating process. The microcapsule cores after compaction and coating using a fluidized-bed coating technique showed a TH-release profile similar to that of the compressed microcapsules after applying hot tabletting process.

CONCLUSIONS

Multi-unit dosage forms can be obtained in a relatively simple way by combining three processes: (i) obtaining TH microcapsule cores by compaction, (ii) coating, and (iii) hot tabletting.