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Quality by Design Empowered Development and Optimisation of Time-Controlled Pulsatile Release Platform Formulation Employing Compression Coating Technology

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ABSTRACT

The research was envisaged for development of time-controlled pulsatile release (PR) platform formulation to facilitate management of early morning chronological attacks. The development was started using prednisone as a model drug wherein core tablets were prepared using direct compression method and subsequently compression-coated with ethylcellulose (EC)-hydroxypropyl methylcellulose (HPMC) excipient blend. Initially, quality target product profile was established and risk assessment was performed using failure mode and effect analysis. In an endeavour to accomplish the objective, central composite design was employed as a design of experiment (DoE) tool. Optimised compression-coated tablet (CCT) exhibited 4–6 h lag time followed by burst release profile under variegated dissolution conditions viz. multi-media, change in apparatus/agitation and biorelevant media. Afterwards, five different drugs, i.e. methylprednisolone, diclofenac sodium, diltiazem hydrochloride, nifedipine and lornoxicam, were one-by-one incorporated into the optimised prednisone formula with replacement of former drug. Change in drug precipitated the issues like poor solubility and flow property which were respectively resolved through formulation of solid dispersion and preparation of active pharmaceutical ingredient (API) granules. Albeit, all drug CCTs exhibited desired release profile similar to prednisone CCTs. In nutshell, tour de force of research epitomised the objective of incorporating diverse drug molecules and penultimately obtaining robust release profile at varying dissolution conditions.

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ACKNOWLEDGEMENTS

Mr. Riddhish Patadia is highly grateful to the University Grants Commission, Government of India, New Delhi for availing senior research fellowship. The authors are thankful to the industries that provided gift samples. We appreciate Metallurgical and Materials Engineering Department, Faculty of Technology and Engineering, The M.S. University of Baroda, Vadodara 390001, India for insightful assistance in PXRD study. We are also thankful to the Electrical Research and Development Association, Vadodara 390010, India for extending support for SEM analysis.

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  1. Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, Gujarat, India

    Riddhish Patadia, Chintan Vora, Karan Mittal & Rajashree C. Mashru

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  1. Riddhish Patadia
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Patadia, R., Vora, C., Mittal, K. et al. Quality by Design Empowered Development and Optimisation of Time-Controlled Pulsatile Release Platform Formulation Employing Compression Coating Technology. AAPS PharmSciTech 18, 1213–1227 (2017). https://doi.org/10.1208/s12249-016-0590-3

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