Multi-kinetics and site-specific release of gabapentin and flurbiprofen from oral fixed-dose combination: in vitro release and in vivo food effect

Sonvico, F; Conti, C; Colombo, G; Buttini, F; Colombo, P; Bettini, R; Barchielli, M; Leoni, B; Loprete, L; Rossi, A

Multi-kinetics and site-specific release of gabapentin and flurbiprofen from oral fixed-dose combination: in vitro release and in vivo food effect

Sonvico, F

Conti, C Colombo, G Buttini, F Colombo, P Bettini, R Barchielli, M Leoni, B Loprete, L Rossi, A

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Publication Type:: Journal Article
Citation:: Journal of Controlled Release, 2017, 262 pp. 296 - 304
Issue Date:: 2017-09-28

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Field	Value	Language
dc.contributor.author	Sonvico, F https://orcid.org/0000-0001-7372-1456	en_US
dc.contributor.author	Conti, C	en_US
dc.contributor.author	Colombo, G	en_US
dc.contributor.author	Buttini, F	en_US
dc.contributor.author	Colombo, P	en_US
dc.contributor.author	Bettini, R	en_US
dc.contributor.author	Barchielli, M	en_US
dc.contributor.author	Leoni, B	en_US
dc.contributor.author	Loprete, L	en_US
dc.contributor.author	Rossi, A	en_US
dc.date.available	2017-07-29	en_US
dc.date.issued	2017-09-28	en_US
dc.identifier.citation	Journal of Controlled Release, 2017, 262 pp. 296 - 304	en_US
dc.identifier.issn	0168-3659	en_US
dc.identifier.uri	http://hdl.handle.net/10453/125135
dc.description.abstract	© 2017 Elsevier B.V. In this work, a fixed-dose combination of gabapentin and flurbiprofen formulated as multilayer tablets has been designed, developed and studied in vitro and in vivo. The aim was to construct a single dosage form of the two drugs, able to perform a therapeutic program involving three release kinetics and two delivery sites, i.e., immediate release of gabapentin, intra-gastric prolonged release of gabapentin and intestinal (delayed) release of flurbiprofen. An oblong three-layer tablet was manufactured having as top layer a floating hydrophilic polymeric matrix for gastric release of gabapentin, as middle layer a disintegrating formulation for immediate release of a gabapentin loading dose and as bottom layer, an uncoated hydrophilic polymeric matrix, swellable but insoluble in gastric fluids, for delayed and prolonged release of flurbiprofen in intestinal environment. The formulations were studied in vitro and in vivo in healthy volunteers. The in vitro release rate assessment confirmed the programmed delivery design. A significant higher bioavailability of gabapentin administered 30 min after meal, compared to fasting conditions or to dose administration 10 min before meal, argued in favor of the gastro-retention of gabapentin prolonged release layer. The two drugs were delivered at different anatomical sites, since the food presence prolonged the gastric absorption of gabapentin from the floating layer and delayed the flurbiprofen absorption. The attainment of a successful delayed release of flurbiprofen was realized by a matrix based on a polymers' combination. The combined use of three hydrophilic polymers with different pH sensitivity provided the dosage form layer containing flurbiprofen with gastro-resistant characteristics without the use of film coating.	en_US
dc.relation.ispartof	Journal of Controlled Release	en_US
dc.relation.isbasedon	10.1016/j.jconrel.2017.07.042	en_US
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.subject.mesh	Intestines	en_US
dc.subject.mesh	Stomach	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Amines	en_US
dc.subject.mesh	gamma-Aminobutyric Acid	en_US
dc.subject.mesh	Flurbiprofen	en_US
dc.subject.mesh	Cyclohexanecarboxylic Acids	en_US
dc.subject.mesh	Polymers	en_US
dc.subject.mesh	GABA Agonists	en_US
dc.subject.mesh	Analgesics	en_US
dc.subject.mesh	Anti-Inflammatory Agents, Non-Steroidal	en_US
dc.subject.mesh	Delayed-Action Preparations	en_US
dc.subject.mesh	Tablets	en_US
dc.subject.mesh	Drug Combinations	en_US
dc.subject.mesh	Administration, Oral	en_US
dc.subject.mesh	Cross-Over Studies	en_US
dc.subject.mesh	Food-Drug Interactions	en_US
dc.subject.mesh	Adolescent	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Young Adult	en_US
dc.subject.mesh	Drug Liberation	en_US
dc.subject.mesh	Gabapentin	en_US
dc.subject.mesh	Gastric Mucosa	en_US
dc.subject.mesh	Intestinal Mucosa	en_US
dc.title	Multi-kinetics and site-specific release of gabapentin and flurbiprofen from oral fixed-dose combination: in vitro release and in vivo food effect	en_US
dc.type	Journal Article
utslib.citation.volume	262	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	0903 Biomedical Engineering	en_US
utslib.for	0904 Chemical Engineering	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
utslib.copyright.status	closed_access
pubs.publication-status	Published	en_US
pubs.volume	262	en_US

Abstract:

© 2017 Elsevier B.V. In this work, a fixed-dose combination of gabapentin and flurbiprofen formulated as multilayer tablets has been designed, developed and studied in vitro and in vivo. The aim was to construct a single dosage form of the two drugs, able to perform a therapeutic program involving three release kinetics and two delivery sites, i.e., immediate release of gabapentin, intra-gastric prolonged release of gabapentin and intestinal (delayed) release of flurbiprofen. An oblong three-layer tablet was manufactured having as top layer a floating hydrophilic polymeric matrix for gastric release of gabapentin, as middle layer a disintegrating formulation for immediate release of a gabapentin loading dose and as bottom layer, an uncoated hydrophilic polymeric matrix, swellable but insoluble in gastric fluids, for delayed and prolonged release of flurbiprofen in intestinal environment. The formulations were studied in vitro and in vivo in healthy volunteers. The in vitro release rate assessment confirmed the programmed delivery design. A significant higher bioavailability of gabapentin administered 30 min after meal, compared to fasting conditions or to dose administration 10 min before meal, argued in favor of the gastro-retention of gabapentin prolonged release layer. The two drugs were delivered at different anatomical sites, since the food presence prolonged the gastric absorption of gabapentin from the floating layer and delayed the flurbiprofen absorption. The attainment of a successful delayed release of flurbiprofen was realized by a matrix based on a polymers' combination. The combined use of three hydrophilic polymers with different pH sensitivity provided the dosage form layer containing flurbiprofen with gastro-resistant characteristics without the use of film coating.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/125135