title: In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.
abstract: The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.
authors.affiliation: University of Strathclyde, Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow, United Kingdom.
authors.forename: Manish
authors.initials: M
authors.lastname: Ghimire
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: McInnes
authors.forename: David G
authors.initials: DG
authors.lastname: Watson
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Mullen
authors.forename: Howard N E
authors.initials: HN
authors.lastname: Stevens
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations; D004285:Dogs; D016503:Drug Delivery Systems; D015195:Drug Design; D041981:Gastrointestinal Tract / Q000187:drug effects; D066298:In Vitro Techniques; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011877:Radionuclide Imaging / Q000379:methods; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D013806:Theophylline / Q000097:blood; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D013607:Tablets; D002482:Cellulose; C008079:hydroxypropylcellulose; D013806:Theophylline