EVALUATION OF KOLLIDON® SR FOR pH-INDEPENDENT EXTENDED RELEASE MATRIX SYSTEMS
The characteristics of a new Polyvinylacetate/Povidone based excipient, Kollidon® SR were evaluated for application in extended release matrix tablets. The effects of the following formulation and process variables on tablet properties and drug release were tested: Kollidon® SR concentration in the tablet, addition of external binder for wet granulation, presence of an enteric polymer in the matrix, method of manufacturing and compression force. The similarities in release profiles were evaluated by applying the model independent f2 similarity factor. A pilot bioequivalence study was performed in human volunteers to confirm in vivo the extended release characteristics of the propranolol tablets manufactured with Kollidon® SR.It was found that Kollidon® SR is suitable for pH-independent extended release matrix tablets. A minimum concentration of 30% polymer was necessary to achieve a coherent matrix, able to extend the release of the incorporated drugs. Increasing the Kollidon® SR concentration in the tablet led to a slower drug release. Drug release followed square root of time dependent kinetics, thus indicating a diffusion-controlled release mechanism. The drug release was influenced by the aqueous solubility of the drug. The drug release rate was faster for wet granulation than direct compression, thus making direct compression the method of choice for manufacturing Kollidon® SR extended release systems. It was found that Kollidon® SR was the main release controlling agent in the presence of an external binder or enteric polymer in the matrix. A significant reduction in the dissolution rates associated with an increase in tablet hardness was observed during the stability test under accelerated conditions.The developed propranolol matrix tablets formulation was compared in a pilot bioequivalence study to the reference listed product (Inderal® LA capsules). It was found that the two products were not bioequivalent according to the FDA bioequivalence criteria. The tablets had higher bioavailability than the capsules as shown by higher Cmax and AUC 0-24h. For the developed tablet formulation the higher initial plasma concentrations correlated with the faster initial release observed in vitro. It was concluded that Kollidon® SR is a potentially useful excipient for the production of pH-independent extended release matrix tablets.
School:University of Cincinnati
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:extended release matrix tablet kollidon® sr
Date of Publication:01/01/2003