RAPID COMMUNICATION Dissolution Profile of Novel Composite Pellet Cores Based on Different Ratios of Microcrystalline Cellulose and Isomalt OLIVER LUHN, 1 NIKOLETT K ´ ALLAI, 2 ZSOMBOR KRIST ´ OF NAGY, 3 KRIST ´ OF KOV ´ ACS, 2 BODO FRITZSCHING, 4 IMRE KLEBOVICH, 2 ISTV ´ AN ANTAL 2 1 S¨ udzucker AG, Central Department Research, Development and Technological Services, Department of Product Technology, Pharmaceutical Technology, Obrigheim 67283, Germany 2 Department of Pharmaceutics, Semmelweis University, Budapest 1092, Hungary 3 Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Budapest 1111, Hungary 4 Department of Sales and Application Technology Pharma, Beneo-Palatinit GmbH, Mannheim 68165, Germany Received 10 January 2012; revised 31 March 2012; accepted 19 April 2012 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jps.23186 ABSTRACT: There is a growing interest towards the application of inert cores as starting materials for pharmaceutical pellet manufacturing. They serve as alternatives to develop and adapt a relatively simple manufacturing technology compared with an extrusion/spheronisation process. The major objective of this study was to investigate the effect of the compositions of core materials on the drug release profile. Pure microcrystalline cellulose (MCC), isomalt and different types of novel composite MCC–isomalt cores were layered with model drug (sodium diclofenac) and were coated with acrylic polymer. The effect of the osmolality in the gastroin- testinal tract was simulated using glucose as osmotically active agent during in vitro dissolution tests. The results demonstrated the dependence of drug dissolution profile on the ratio of MCC and isomalt in the core and the influence of osmotic properties of the dissolution medium. Iso- malt used in the composite core was able to decrease the vulnerability of the dissolution kinetics to the changes in the osmotic environment. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci Keywords: inert pellet core; isomalt; microcrystalline cellulose; osmolality; dissolution; excipients; factorial design; solid dosage form; drug delivery systems INTRODUCTION There is a growing interest towards the application of multiparticulate systems, for example, pellets as multi-unit dosage forms. 1 Although different materi- als are often combined in matrix pellets to optimise quality, layered pelletizing allows a simple manufac- turing technology wherein a drug is loaded onto in- ert starting cores. Starter inert cores have several technological benefits such as they serve as nuclei with standardised shape. Up to the present, basically pure types of inert cores have been commercially ap- plied such as water-soluble carbohydrates (e.g., sugar, isomalt) and water-insoluble microcrystalline cellu- Correspondence to: Istv´ an Antal (Telephone: +36-1-2170914; Fax: +36-1-2170914; E-mail: antist@gyok.sote.hu) Journal of Pharmaceutical Sciences © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association lose (MCC), which offer different characteristics and processability. 2 Higher yield without the formation of undesirable agglomerates was observed for cores composed of MCC because of their insolubility in wa- ter during drug layering. 3 Consequently, MCC serves as a commonly used ex- cipient for both inert cores or filler and spheronisa- tion enhancer for matrix pellets, despite the disad- vantages including drug adsorption to the surface, chemical incompatibility with a number of drugs and lack of disintegration. 4–6 Isomalt is a water-soluble polyol, which is promising for pharmaceutical pur- poses (suitable for diabetics and non-cariogenic). 7,8 Literature data prove that the drug release from matrix pellets is also a function of the composition of the materials building up the pellets. 9,10 Our pre- vious study demonstrated that the inert core mate- rial plays a significant role in the drug release as the JOURNAL OF PHARMACEUTICAL SCIENCES 1