title: A new ternary polymeric matrix system for controlled drug delivery of highly soluble drugs: I. Diltiazem hydrochloride.
abstract: OBJECTIVE
  The purpose of this study was to develop a new ternary polymeric matrix system that is easy to manufacture and that delivers a highly soluble drug over long periods of time.
  
  
  METHODS
  Pectin, hydroxypropylmethylcellulose (HPMC), and diltiazem HCl granulated with gelatin at optimized ratios were blended at different loading doses and directly compressed. Swelling behavior, dissolution profiles and the effect of hydrodynamic stress on release kinetics were evaluated.
  
  
  RESULTS
  Diltiazem release kinetics from the ternary polymeric system was dependent on the different swelling behavior of the polymers and varied with the drug loading dose and hydrodynamic conditions. Drug release followed either non-Fickian or Case II transport kinetics. The relative influence of diffusion and relaxational/dissolution effects on release profiles for different drug loadings was calculated by a nonlinear regression approach. Photographs taken during swelling show that the anisotropic nature of the gel structure, drug loading dose, swelling capacity of polymers used, and the design of delivery system all play important roles in controlling the drug release and dissolution/erosion processes.
  
  
  CONCLUSIONS
  Zero-order delivery of diltiazem HCl from a simple tablet matrix was achieved. The ternary polymeric system developed in this study is suitable for controlled release of highly soluble drugs. It offers a number of advantages over existing systems, including ease of manufacturing and of release modulation, as well as reproducibility of release profiles under well defined hydrodynamic conditions. Our delivery system has the potential to fully release its drug content in a controlled manner over a long time period and to dissolve completely.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, Pennsylvania 19140, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: R
authors.initials: R
authors.lastname: Fassihi
mesh_terms: D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D005780:Gelatin / Q000737:chemistry*; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D010368:Pectins / Q000737:chemistry*; D012995:Solubility; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D065347:Hypromellose Derivatives; D010368:Pectins; D005780:Gelatin; D008747:Methylcellulose; D004110:Diltiazem