In vitro and in vivo evaluation of multilayered pastilles for chronotherapeutic management of nocturnal asthma

Abstract

Objective: The present work was undertaken with an objective to design a multilayered dosage form of doxofylline, using pastillation technology, for the chronotherapeutic management of nocturnal asthma.

Research design & methods: Pastilles consisting of the drug, polyethylene glycol and colloidal silicon dioxide, were generated using an in-house laboratory-scale pastillation device. The pastilles were further coated with enteric polymers and a floating layer, using conventional coater. The pastilles were subjected to physicochemical analysis, morphological characterization, in vitro drug release studies and in vivo pharmacokinetic studies in rats.

Results: It was observed that colloidal silicon dioxide was instrumental in improving the contact angle of the pastilles. The uncoated pastilles released the drug immediately, while the enteric-coated (10% w/w) pastilles were found to have sufficient acid resistance when the coat is applied with 5% (v/v) triethyl citrate as plasticizer. The in vivo blood serum profile indicated that the pastilles coated with the enteric coat and the additional floating coat were effective in significantly delaying the in vivo drug release required for the chronotherapeutic treatment of nocturnal asthma.

Conclusion: The present work opens a new alternative to the conventional tablet or capsule dosage form for the development of both immediate-release and modified-release drug delivery systems.

Keywords:

• chronotherapeutic management
• doxofylline
• enteric coating
• nocturnal asthma
• pastillation

Notes