Felodipine β-cyclodextrin complex as an active core for time delayed chronotherapeutic treatment of hypertension

Abstract

The key to the success of any drug delivery system depends upon the development of formulations that accomplish the therapeutic needs associated with a particular pathological condition or disease state (1). Many physiological body functions (e.g., blood The present research work deals with the development of a time delayed chronotherapeutic formulation of felodipine (FD) aimed at rapid drug release after a desired lag time in the management of hypertension. The developed system comprises a drug core embedded within a swellable layer and coated with an insoluble, water permeable polymeric system. FD cyclodextrin complex was used as an active core while ethyl cellulose was used as an effective coating layer. Dissolution studies of the complex revealed that there was a 3-fold increase in dissolution of the complex compared to plain FD. This dissolution enhancement and rapid drug release resulted from FD amorphisation, as confirmed by XRD, DSC and SEM studies. FTIR and 1 H NMR studies confirmed the complex formation between FD and cyclodextrin based on the observed hydrogen bond interactions. FD release was adequately adjusted by using a pH independent polymer, i.e., ethyl cellulose, along with dibutyl phthalate as plasticizer. Influence of formulation variables like polymer viscosity, plasticizer concentration, super disintegrant concentration in the swellable layer and percent coating weight gain was investigated to characterize the lag time. Upon permeation of water, the core tablet swelled, resulting in the rupture of the coating layer, followed by rapid drug release. The developed formulation of FD showed a lag time of 5-7 h, which is desirable for chronotherapeutic application.

Multicomponent solid forms of felodipine: preparation, characterisation, physicochemical and in-vivo studies

“…However, it suffers from poor aqueous solubility (19.7 mg/l) and low bioavailability (15–20%) and belongs to class II drugs according to the Biopharmaceutical Classification System (BCS) . Few attempts have been employed to improve dissolution of FEL by preparing self‐nanoemulsifying delivery system, solid dispersions, amorphous forms and complexation with beta‐cyclodextrin . However, all these approaches suffer from certain limitation such as agglomeration, an increase in bulk size due to high molecular weight polymers, polymorphic conversion and susceptibility of devitrification in the glassy state.…”

Novel Chronotherapeutic Multiparticulate Drug Delivery System of Felodipine: an Effective Treatment for Cardiac Arrhythmia

“…Considering this fact, reports abound in the literature describing various attempts to increase the solubility and dissolution of the drug substance (Karavas et al, 2005;Alonzo et al, 2011;Basalious et al, 2011). Approaches like nanodispersion (Karavas et al, 2006) and β-cyclodextrin (Pagar and Vavia, 2012) complexation have been employed for the purpose. However, neither of the two approaches are effective enough to render the drug substance completely amorphous.…”

“…Literature reports some of the approaches that have been followed to formulate chronotherapeutic systems of calcium channel blockers (CCBs), one of the most promising therapeutic options for cardiac arrhythmia (Karavas, et al, 2006;Pagar and Vavia, 2012). However, these approaches basically focus on combining three to four sequentially coated tablets into one capsule formulation.…”

Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system

“…Many papers have reported the development of pulsatile chronopharmaceutical systems (1,7,9,10), in some of which design of experiments was used (2,13,20), but so far the use of piecewise function parameters for characterization of the dissolution profile shape has not been reported. The advantage of using piecewise function is precise characterization of the pulsatile release profile by two turning points of the sigmoid shape.…”

“…Chronotherapy is the delivery of a drug at the right concentration to the right targeted tissues at the right time to meet the biological rhythm-determined needs (1)(2)(3). Blood pressure is characterized by predictable changes over 24 hours in synchrony with the rest-activity cycle.…”