Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets

Novel calcium phosphate-based starter pellets were used to develop a biphasic-release multiple-unit pellet system (MUPS) with diclofenac sodium as a model drug in the form of hard gelatin capsules. For comparative purposes, corresponding formulations based on the inert cores made of microcrystalline cellulose, sucrose and isomalt were prepared. The developed system consisted of two types of drug-layered pellets attaining different release patterns: delayed-release (enteric-coated) and extended-release. Dissolution characteristics were examined using both compendial and biorelevant methods, which reflected fed and fasting conditions. The results were collated with an equivalent commercial product but prepared with the direct pelletization technique.

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or continue reading here: Zakowiecki, D.; Frankiewicz, M.; Hess, T.; Cal, K.; Gajda, M.; Dabrowska, J.; Kubiak, B.; Paszkowska, J.; Wiater, M.; Hoc, D.; Garbacz, G.; Haznar-Garbacz, D. Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets. Pharmaceutics 2021, 13, 805. https://doi.org/10.3390/pharmaceutics13060805

Materials and Methods
Diclofenac sodium (Amoli Organics, Mumbai, India). Inert cores: calcium phosphate-based (DCPA) pellets—PharSQ® Spheres CM M (Chemische Fabrik Budenheim, Budenheim, Germany), microcrystalline cellulose pellets—VIVAPUR® MCC Spheres 500 (JRS Pharma, Rosenberg, Germany), sugar spheres—pharm-a-spheresTM MESH 35-25 (Hanns G. Werner GmbH, Tornesch, Germany), isomalt starter pellets—galenIQTM 960 (BENEO-Palatinit GmbH, Mannheim, Germany). Film coating systems: Vivacoat® FM-1M 000 (JRS Pharma, Rosenberg, Germany), Aquarius® Control ENA (Ashland, Covington, KY, USA), Eudragit® RL30D and Eudragit® RS30D (Evonik, Darmstadt, Germany). Transparent hard gelatin capsule shells, size “00” (Pharmapol Arzneimittelvertrieb GmbH, Dägeling, Germany). DicloDuo® 75 mg, modified-release capsules (Pharmaswiss Česká republika s.r.o., Praha, Czech Republic).

Conclusions
The aim of this study was to develop multi-unit biphasic release systems (BPR MUPS) for diclofenac sodium using different types of neutral starter pellets. A series of performance tests demonstrated that control of the dissolution of the drug substance from the developed formulations was clearly related to the water solubility of their inert cores. It was observed that the water-insoluble starter pellets (MCC spheres and DCPA-based pellets) were able to control the rate of release much better than soluble sugar spheres or isomalt pellets. In the case of the latter, it can be assumed that the use of more efficient polymers or a greater amount of them would result in a decrease in the dissolution rate. In this respect, MCC and DCPA starter pellets offer a very attractive opportunity of improving productivity and controlling the dissolution rate of drugs with a smaller quantity of polymers. Calcium phosphate-based pellets appear to be a particularly promising prospect.