title: Characterization of 5-fluorouracil release from hydroxypropylmethylcellulose compression-coated tablets.
abstract: Hydrogel compression-coated tablets are able to release the core drug after a period of lag time and have potential for colon-specific drug delivery based on gastrointestinal transit time concept. This study investigated the factors influencing in vitro release characteristics of a model drug 5-fluorouracil from hydroxypropylmethycellulose (HPMC) compression-coated tablets. The core tablet, prepared by a wet granulation compression method, was designed to disintegrate and dissolute quickly. To prepare the compression-coated tablets, 50% of the HPMC/lactose coat powder was precompressed first, followed by centering the core tablet and compressing with the other 50% of the coat powder. Release characteristics were evaluated in distilled water by using a Chinese Pharmacopoeia rotatable basket method. Effect of HPMC viscosity, lactose content in outer shell, and overall coating weight of outer shell on release lag time (T(lag)), and zero-order release rate (k) were studied. Release of drug from compression-coated tablets began after a time delay as a result of hydrogel swelling/retarding effect, followed by zero-order release for most of the formulations studied. HPMC of higher viscosity (K4M and K15M) provided better protection of the drug-containing core, showing increased release lag time and slower release rate. Incorporating lactose in outer shell led to decrease of T(lag) and increase of k. T(lag) and k are exponentially and linearly correlated to lactose content, expressed as weight percentage of the outer shell. Larger coating weight (W) of outer shell produced larger coating thickness (D) around core tablet, which resulted in increase in T(lag) and decrease in k. There was good fitting of a linear model for each of the four variables W, D, T(lag), and k. Hardness of the compression-coated tablets and pHs of the release media had little effect on drug release profile. It is concluded that the release lag time and release rate are able to be tailored through adjusting the formulation variables to achieve colon-specific drug delivery of 5-fluorouracil.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Baojian
authors.initials: B
authors.lastname: Wu
authors.forename: Ningyun
authors.initials: N
authors.lastname: Shun
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry*; D003106:Colon / Q000378:metabolism; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry*; D006244:Hardness; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D007700:Kinetics; D007785:Lactose / Q000737:chemistry; D016014:Linear Models; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D013608:Tablets, Enteric-Coated; D014783:Viscosity
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D005079:Excipients; D020100:Hydrogels; D013608:Tablets, Enteric-Coated; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D007785:Lactose; D005472:Fluorouracil