In vitro and in vivo evaluation of an oral multi-layered multi-disk tablet for specialized chronotherapeutic drug delivery

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Authors

Khan, Zaheeda
Govender, Mershen
Indermun, Sunaina
Kumar, Pradeep
Choonara, Yahya E.
Du Toit, Lisa C.
Meyer, Leith Carl Rodney
Pillay, Viness

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Volume Title

Publisher

Elsevier

Abstract

Chronotherapeutic disorders such as hypertension, cardiovascular disease and asthma commonly involve the use of controlled zero-order release formulations. Ideally, the required drug should be released at predetermined rates with two or more pulses released from the dosage form. This ultimately exposes the patient to drug only when required, reducing the number of dosages, reducing side-effects and increasing patient compliance. The aim of this research was to evaluate two Multi-Layered Multi-Disk Tablet (MLMDT) systems incorporating drug-loaded disks enveloped by three polymeric layers. The model drugs used for each system were theophylline and diltiazem hydrochloride. The proposed chronotherapeutic system was designed to provide a lag phase and then two pulses of drug release separated by a ‘switch-off’ phase. In vitro drug release analysis revealed that the MLMDT generated a lag phase or a ‘switch-off’ phase followed by two pulses of drug release over the evaluated 24 h period. In vivo testing was undertaken using a Large White Pig Model, where concentration analysis from the evaluated conventional products revealed increasing plasma concentrations up to 2 h followed by a steady decline in concentration while the developed MLMDT displayed two pulse prolonged drug release profile separated by a switch-off phase.

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Keywords

Chronotherapeutics, Multi-layered multi-disk tablet (MLMDT), Drug delivery, Switch-off phase, Metabolism, Pigs

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Citation

Khan, Z., Govender, M., Indermun, S. et al. 2018, 'In vitro and in vivo evaluation of an oral multi-layered multi-disk tablet for specialized chronotherapeutic drug delivery', Journal of Drug Delivery Science and Technology, vol. 45, pp. 39-44.