Novel formulation and processing aspects for compression coated tablets and for the compression of polymer-coated multiparticulates

To achieve compression of polymer-coated pellets into tablets, good flexibility of the polymeric coating is crucial in order not to rupture and to loose the modified release properties. Enteric polymers are quite brittle in the dry state and thus not suitable as pellet coatings for compression into tablets. The objective of this study was to investigate the role of humidity treatment prior to compression and thus the role of moisture as potent plasticizer for the successful compression of enterically coated pellets. Eudragit L30D-55 coated pellets were stored at different humidities for different time periods and then compressed and evaluated for changes in acetaminophen release. The damage to the Eudragit L-coated pellets decreased with increasing storage humidity and storage time, as indicated by a lower increase in release upon compression. A higher storage humidity resulted in an increased water content and plasticization effect of the films as indicated by a decrease in the glass transition temperature of films. Second, pH-erosion controlled compression-coated tablets for potential colonic drug delivery with improved gastric resistance and pulsatile release based on compression- coatings of powder blends of the enteric polymer Eudragit L 100-55 and ethylcellulose (EC) were studied. Tablet cores containing model drugs (acetaminophen, carbamazepine, propranolol HCl and chlorpheniramine maleate) were compression-coated with different ratios of Eudragit L100-55: EC at different compression forces and tablet core:coat ratios. Pulsatile drug release in higher pH-media after a lag time, which was controlled by the erosion of the Eudragit L: EC compression-coating. The addition of EC avoided premature drug release in lower pH-media and significantly increased the lag time in higher pH-media because of a reduction in wettability, media uptake and erosion of the compression-coatings. Third, flexible extended drug release profiles with hydroxypropyl methylcellulose (HPMC) compression-coated tablets could be obtained. The HPMC-compression-coating resulted in release profiles with a distinct lag time followed by different release phases primarily determined by the drug solubility. Carbamazepine, a water-insoluble drug, was released in a pulsatile fashion after erosion of the HPMC compression-coat, while the more soluble drugs were released in a sigmoidal fashion by diffusion through the gel prior to erosion. With carbamazepine, increasing the molecular weight of HPMC significantly increased the lag time because of the erosion- based release mechanism, while, in contrast, molecular weight did not affect the release of the more soluble drugs. The lag-time and the release rate could also be well controlled by varying the HPMC amount in and the thickness of the compression-coating. A pulsatile release could be achieved for water-soluble drugs by introducing an enteric polymer coating between the drug core and the HPMC compression-coating to eliminate drug diffusion through the gelled HPMC layer prior to its erosion. The lag time increased with increasing Eudragit L coating because of a slower dissolution of the thicker coating. Pulsatile release was obtained with the lower molecular weight HPMC E50 and 400, but extended release with longer lag time with from HPMC K4M. Incorporating drug in the compression-coating and tablet core in varying ratios resulted in release profiles with increasing, decreasing or constant release rates.