Graduation date: 2007
Hot-melt pan-coating, which is a novel coating method and takes 2-3 hours for 300 mg coating weight gain per capsule and tamper-resistant coating, which takes 30 minutes, is much faster than tedious sugar coating and allows greater coating weight gains in shorter times than spray-melt coating. Although hot-melt pan coating is promising, it needs modification for industrial scale-up and to provide more elegant formulations.
Hot-melt capsule filling is an especially appealing and simple way to make sustained release formulations.
A novel formulation of glipizide developed comprising compression of four-layer coated beads into tablets has advantages of keeping sustained-release characteristics following a lag time, providing approximately zero-order release, and releases drug nearly independent of paddle speeds 50 and 100 rpm. The amount of binding and disintegration ingredients can be adjusted to produce appropriate disintegration times for tablets and to release individually coated particulates. Formulation CH20 tablet, matched the dissolution pattern of Glucotrol-XL osmotic pump tablets in two pH media at 100 rpm paddle, and dissolution patterns of Glucotrol XL and CH20 tablet were close to each other at 50, 150 and 200 rpm paddle. This formulation is predicted by convolution simulation to be bioequivalent to Glucotrol-XL in-vivo.
A novel bead formulation of verapamil was developed comprising a combination of extrusion and spheronization to produce a relatively high drug load, followed by coating with an insoluble polymer (ethylcellulose) that contains a water soluble channeling agent (lactose), thus allowing a sufficiently thick coating to be uniform and robust without “shutting down” release of the relatively insoluble drug. Formulation OSU2, provided the unexpected benefit where by adjusting the coating thickness and ethylcellulose/lactose ratio, it is possible to obtain essentially non-agitation sensitive and zero-order drug release up to 14 hours in either KCl or two different pH media at stirring speeds of either 75 or 200 rpm with the USP basket or paddle stirring method. This formulation matched the dissolution pattern of Verelan-PM capsules with basket method and paddle method in KCl medium, and two pH medium methods at different speeds and is predicted by convolution simulation to be bioequivalent to Verelan-PM in-vivo.