Multiple unit gastroretentive drug delivery systems: a new preparation method for low density microparticles.
The aim of this study was to develop a new preparation method for low density foam-based, floating microparticles and to demonstrate the systems' performance in vitro. Major advantages of the novel preparation technique include: (i) short processing times, (ii) no exposure of the ingredients to high temperatures, (iii) the possibility to avoid toxic organic solvents, and (iv) high encapsulation efficiencies close to 100%. Floating microparticles consisting of polypropylene foam powder, model drug [chlorpheniramine maleate (CPM), diltiazem HCl, theophylline or verapamil HCl] and polymer [Eudragit RS or polymethyl methacrylate (PMMA)] were prepared by soaking the microporous foam carrier with an organic solution of drug and polymer and subsequent drying. The effects of various formulation and processing parameters on the resulting in vitro floating behaviour, internal and external particle morphology, drug loading, in vitro drug release and physical state of the incorporated drug were studied. Good in vitro floating behaviour was observed in most cases and a broad variety of drug release patterns could be achieved by varying the drug loading and type of polymer. Interestingly, PMMA-based microparticles showed incomplete drug release with verapamil HCl. This restriction could be overcome by forming the free base of the drug prior to microparticle preparation. In contrast to the salt, the free base acted as a plasticizer for PMMA, resulting in sufficiently high diffusion coefficients and, consequently, complete drug release. The low density microparticles were compressed into rapidly disintegrating tablets in order to provide an administrable oral dosage form.
Streubel
A
A
College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
Siepmann
J
J
Bodmeier
R
R
D000284:Administration, Oral; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D005753:Gastric Mucosa / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011109:Polymethacrylic Acids / Q000737:chemistry; D019904:Polymethyl Methacrylate / Q000737:chemistry
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005765:Gastrointestinal Agents; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D019904:Polymethyl Methacrylate