Enteric polymers as binders and coating materials in multiple-unit site-specific drug delivery systems.
The aim of this study was to develop a multiple-unit, site-specific drug formulation allowing targeting of drug release in the colon. Initially, characteristics of matrix pellets containing various enteric polymers as binders were tested. An enteric coating was then added to the formulations. Ibuprofen and furosemide were used as model drugs. The former is absorbed throughout the gastrointestinal tract, the latter only from upper parts. Methacrylate copolymers, hydroxypropyl methylcellulose acetate succinates and cellulose acetate phthalate were used as enteric polymers. The properties of the products were initially tested via dissolution studies at different pHs, then via bioavailability studies in healthy volunteers. The main conclusion was that drug release can be targeted on the distal part of the small intestine and the colon by preparing film-coated matrix pellets in which enteric polymers dissolving at pH approximately 7 have been used both as binders in the pellets and as coating material. This conclusion is based on the finding that absorption of ibuprofen from the formulations developed was adequate, with a lag-time of about 2 h and tmax values at 4-5 h, where as absorption of furosemide from the analogous products was negligible. It was also found that uncoated pellets as such could represent a slow-release formulation for furosemide, a problem drug as far as modified-release products are concerned.
Marvola
M
M
Division of Biopharmaceutics and Pharmacokinetics, Department of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland.
Nykänen
P
P
Rautio
S
S
Isonen
N
N
Autere
A
A
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D011108:Polymers; D012995:Solubility
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004232:Diuretics; D005079:Excipients; D011108:Polymers; D005665:Furosemide; D007052:Ibuprofen