Zero-order delivery of a highly soluble, low dose drug alfuzosin hydrochloride via gastro-retentive system.
A composite gastro-retentive matrix for zero-order delivery of highly soluble drug alfuzosin hydrochloride (10mg) has been designed and characterized. Two systems containing polyethylene oxide (PEO), hydroxypropylmethylcellulose (HPMC), sodium bicarbonate, citric acid and polyvinyl pyrrolidone were dry blended and compressed into triple layer and bi-layer composite matrices. Dissolution studies using the USP 27 paddle method at 100 and 50rpm in pH 2.0 and 6.8 were performed using UV spectroscopy at 244nm, with automatic sampling over a 24h period using a marketed product as a reference to calculate the "f(2)" factor. Textural characteristics of each layer, the composite matrix as a whole, and floatation potential were determined under conditions similar to dissolution. Percent matrix swelling and erosion along with digital images were also obtained. Both systems proved to be effective in providing prolonged floatation, zero-order release, and complete disentanglement and erosion based on the analysis of data with "f(2)" of 68 and 71 for PEO and HPMC based systems, respectively. The kinetics of drug release, swelling and erosion, and dynamics of textural changes during dissolution for the designed composite systems offer a novel approach for developing gastro-retentive drug delivery system that has potential to enhance bioavailability and site-specific delivery to the proximal small intestine.
Liu
Quan
Q
Department of pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia 19140, USA.
Fassihi
Reza
R
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D019563:Mechanics; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011799:Quinazolines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013607:Tablets; D014867:Water / Q000737:chemistry
D000317:Adrenergic alpha-Antagonists; D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D011799:Quinazolines; D013607:Tablets; D014867:Water; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D002482:Cellulose; D008747:Methylcellulose; C047638:alfuzosin; C008079:hydroxypropylcellulose