Development and evaluation of oral multiple-unit and single-unit hydrophilic controlled-release systems.
This study compared the release behavior of single-unit (tablets, capsules) and multiple-unit (minitablets in capsules) controlled-release systems of furosemide. The swelling and erosion behaviors of these systems, which contained the swellable hydrophilic polymers sodium alginate (high viscosity) and Carbopol 974P, were compared. Swelling and erosion experiments showed a high degree of swelling and limited erosion for the Carbopol preparations, whereas less swelling but greater erosion was observed for the sodium alginate preparations. The sodium alginate preparations were eroded in 6 hours, while Carbopol preparations exhibited limited erosion within this period of time. These results appear to be attributed to the physicochemical characteristics of the polymers used in this study. Polymer characteristics greatly influenced the release of furosemide (model drug) from the formulations prepared and tested. Sodium alginate had a less pronounced sustained release effect compared with Carbopol (ie, in 8 hours all 3 sodium alginate dosage forms displayed complete release of furosemide, while only 30% of the drug was released from Carbopol dosage forms). Finally, all 3 Carbopol dosage forms (single- and multiple-unit) displayed similar release behavior while sodium alginate dosage forms displayed a different and more distinctive behavior. Minitablets and tablets showed a greater sustained release effect compared with capsules. Evaluation of the release data indicates that the release mechanism for sodium alginate formulations may be attributed to erosion/dissolution, while for Carbopol it may be attributed mainly to polymer relaxation and diffusion of the drug from the polymer surface.
Efentakis
M
M
School of Pharmacy, Department of Pharmaceutical Technology, University of Athens, Panepistimiopolis, Zografou, 157 71 Athens, Greece. efentakis@pharm.uoa.gr
Koutlis
A
A
Vlachou
M
M
D000180:Acrylic Resins; D000464:Alginates / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism*; D004304:Dosage Forms; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D015195:Drug Design; D005069:Evaluation Studies as Topic; D005665:Furosemide / Q000737:chemistry / Q000378:metabolism*; D020723:Glucuronic Acid / Q000737:chemistry / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D011145:Polyvinyls / Q000737:chemistry / Q000378:metabolism; D013607:Tablets / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry
D000180:Acrylic Resins; D000464:Alginates; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004337:Drug Carriers; D006603:Hexuronic Acids; D011145:Polyvinyls; D013607:Tablets; D014867:Water; C006912:carboxypolymethylene; D005665:Furosemide; D020723:Glucuronic Acid