Abstract
The present study was aimed at the development of gastroretentive floating pulsatile release tablets (FPRTs) of lercanidipine HCl to enhance the bioavailability and treat early morning surge in blood pressure. Immediate release core tablets containing lercanidipine HCl were prepared and optimized core tablets were compression-coated using buoyant layer containing polyethylene oxide (PEO) WSR coagulant, sodium bicarbonate, and directly compressible lactose. FPRTs were evaluated for various in vitro physicochemical parameters, drug-excipient compatibility, buoyancy, swelling, and release studies. The optimized FPRTs were tested in vivo in New Zealand white rabbits for buoyancy and pharmacokinetics. DoE optimization of data revealed FPRTs containing PEO (20% w/w) with coat weight 480 mg were promising systems exhibiting good floating behavior and lag time in drug release. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. A quadratic model was suggested for release at 7th and 12th h and a linear model was suggested for release lag time. The FPRT formulation improved pharmacokinetic parameters compared to immediate release tablet formulation in terms of extent of absorption in rabbits. As the formulation showed delay in drug release both in vitro and in vivo, nighttime administration could be beneficial to reduce the cardiovascular complications due to early morning surge in blood pressure.
Highlights
The oral route is the common way for consumption of drugs among various routes of drug administration due to the patient compliance and cost involved in therapy
In order to improve the bioavailability, rapid absorption of the lercanidipine HCl is essential for the gastric region as soon as it gets released from the dosage form
There was no significant difference between clearance, half-life, and rate elimination between floating pulsatile release tablets (FPRTs) and immediate release formulations. These results indicate that FPRT (FP 14) shows delayed pulsatile release of lercanidipine HCl rather than considerable increase in the bioavailability of drug
Summary
The oral route is the common way for consumption of drugs among various routes of drug administration due to the patient compliance and cost involved in therapy. The increase in intimate contact of the dosage form with the GIT membrane has the prospective to enhance rate and extent of drug absorption [2]. Many approaches are used to enhance gastric residence time such as swellable systems, mucoadhesive formulations, and altering the density of dosage forms [1, 3]. Floating drug delivery systems (FDDS) based on low density for gastric retention have been studied widely and are designed to float on stomach fluid while releasing the drug slowly at predetermined rate from the delivery system [2,3,4,5]. Based on the mechanism of floating behavior, noneffervescent and effervescent systems are studied widely for FDDS.
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