title: Quality by Design Empowered Development and Optimisation of Time-Controlled Pulsatile Release Platform Formulation Employing Compression Coating Technology.
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.
authors.affiliation: Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, Gujarat, India.
authors.forename: Riddhish
authors.initials: R
authors.lastname: Patadia
authors.affiliation: Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, Gujarat, India.
authors.forename: Chintan
authors.initials: C
authors.lastname: Vora
authors.affiliation: Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, Gujarat, India.
authors.forename: Karan
authors.initials: K
authors.lastname: Mittal
authors.affiliation: Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, 390001, Gujarat, India. rajshreemashru@yahoo.com.
authors.forename: Rajashree C
authors.initials: RC
authors.lastname: Mashru
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D005079:Excipients; D065347:Hypromellose Derivatives; D011241:Prednisone / Q000008:administration & dosage / Q000737:chemistry; D011312:Pressure; D018570:Risk Assessment; D012995:Solubility; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; D065347:Hypromellose Derivatives; C013517:ethyl cellulose; D002482:Cellulose; D011241:Prednisone
keywords: burst release; chronotherapeutics; failure mode and effect analysis; lag time; risk assessment