RESUMEN
Aims: The purpose of this research is to develop a novel expandable gastroretentive dosage form (GRDF), based on unfolding mechanism. It consists of a drug loaded bilayer polymeric film, folded into a hard gelatin capsule. Gastric retention is achieved due to unfolding of the dosage form within 15-20 min. Furosemide is selected as the drug candidate for this work. Due to its narrow absorption window, Furosemide has to be administered to the upper parts of the intestine in order to maintain sustained therapeutic levels. This may be achieved by a GRDF. Methodology: Films were prepared by solvent-casting technique using Ethyl cellulose, HPMC E15 and Eudragit RLPO as polymers and dibutyl phthalate as the plasticizer in both layers. The film with zigzag folding in the capsule was shown to unfold in the gastric juice and provide drug release up to 12 h in the acidic medium. The films were evaluated for weight & thickness variation, mechanical properties, in vitro drug release and unfolding behavior based on the mechanical shape memory of polymers. Absence of drug polymer interaction and uniform drug dispersion in the polymeric layers was revealed by DSC, XRD studies and SEM. The GRDF location in the gastrointestinal tract was determined by X-ray studies. Results: X-ray studies revealed that the GRDF is retained in the stomach up to 6± 0.5 h in fasting condition and 8 h in fed state. Conclusion: The polymers used in the development of GRDFs were safe and proper combination of these polymers will yield a novel expandable GRDF with good in vitro drug release in acidic media, mechanical properties, and unfolding behaviour. These outcomes demonstrate that the GRDF may be used to improve furosemide therapy and can be applied to extend the absorption of other narrow absorption window drugs that require continuous input.
RESUMEN
Verapamil Hydrochloride is a calcium channel blocking anti-anginal agent. Extensive first pass metabolism, low bioavailability (~20%) and short biological half life (4.8 hrs) altogether makes it an ideal candidate for transdermal drug delivery. The objectives of this study were to develop matrix-type transdermal patches of verapamil hydrochloride (VPL) with combinations of hydroxypropyl methyl cellulose (HPMC) and hydroxy propyl cellulose (HPC) as matrix polymers and to investigate the influence of oleic acid (OA) on in vitro permeation of VPL through rat skin. The permeation studies were performed using Franz-type diffusion cells and full-thickness excised abdominal rat skin. The effect of the polymers on the drug release, percentage moisture loss, percentage moisture absorption, folding endurance, and thickness, were investigated.. In vitro release studies showed zero-order release of the drug from all the patches, and the mechanism of release was diffusion mediated. Data was analysed using different release kinetic models. In vitro release profiles showed that from optimized combination the release of the drug was sustained and it extended over a period of 24 hr VPM 006 emerged as the most satisfactory formulation as far as its technological properties were concerned.