title: Film-coated matrix mini-tablets for the extended release of a water-soluble drug.
abstract: Extended release (ER) of water-soluble drugs from hydroxypropylmethylcellulose (HPMC) matrix mini-tablets (mini-matrices) is difficult to achieve due to the large surface area to volume ratio of the mini matrices. Therefore, the aims of this study were to control the release of a water-soluble drug (theophylline) from mini-matrices by applying ER ethylcellulose film coating (Surelease®), and to assess the effects of Surelease®:pore former (Opadry®) ratio and coating load on release rates. Mini-matrices containing 40%w/w HPMC K100M CR were coated with 100:0, 85:15, 80:20, 75:25 or 70:30 Surelease®:Opadry® to different coating weight gains (6-20%). Non-matrix mini-tablets were also produced and coated with 80:20 Surelease®:Opadry® to different coating weight gains. At low coating weight gains, nonmatrix mini-tablets released the entire drug within 0.5 h, while at high coating weight gains only a very small amount (<5%) of drug was released after 12 h. The gel formation of HPMC prevented disintegration of mini-matrices at low coating weight gains but contributed to rupture of the film even at high coating weight gains. As a result, drug release from mini-matrices was slower than that from nonmatrix mini-tablets at low coating weight gains, yet faster at high coating weight gains. An increase in the lag time of drug release from mini-matrices was observed as the concentration of Opadry® reduced or the coating weight gain increased. This study has demonstrated the possibility of extending the release of a water-soluble drug from HPMC mini-matrices by applying ER film coating with appropriate levels of pore former and coating weight gains to tailor the release rate.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University , Liverpool , UK and.
authors.forename: Faiezah A A
authors.initials: FA
authors.lastname: Mohamed
authors.forename: Matthew
authors.initials: M
authors.lastname: Roberts
authors.forename: Linda
authors.initials: L
authors.lastname: Seton
authors.forename: James L
authors.initials: JL
authors.lastname: Ford
authors.forename: Marina
authors.initials: M
authors.lastname: Levina
authors.forename: Ali R
authors.initials: AR
authors.lastname: Rajabi-Siahboomi
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000648:ultrastructure; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D065347:Hypromellose Derivatives / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D016062:Porosity; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D013806:Theophylline / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; C000604285:Opadry II 85; D010726:Phosphodiesterase Inhibitors; D011145:Polyvinyls; D013607:Tablets; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; C013517:ethyl cellulose; D011142:Polyvinyl Alcohol; D002482:Cellulose; D013806:Theophylline; C000595212:polyethylene glycol 3350
keywords: Ethylcellulose; HPMC; film coating; hypromellose; mini-matrices; theophylline