Chitosan-carboxymethylcellulose interpolymer complexes for gastric-specific delivery of clarithromycin.
Chitosan (CS) and carboxymethylcellulose (CMC) sodium interpolymer complexes were formed using the novel method "tablets-in-capsule" for stomach drug delivery. The aim of this study was to investigate the influence of the molecular weight (M.wt.) of CS and the proportion CS/CMC on physical properties and clarithromycin (CAM) release. Swelling was dependent on CS M.wt., on medium pH and on proportion polymer/polymer. The higher M.wt., the major presence of protonated amined moieties that can be ionized and modify the swelling/eroding and dissolution medium uptake capacity. Swelling kinetics at pH 1.2, were close to Fickian diffusion, whereas at pH 4.2 were non-Fickian. Furthermore, dissolution medium uptake capacity can be adjusted to an exponential equation at pH 1.2 (r2> or =0.96), and to a linear equation at pH 4.2 (r2> or =0.99), showing that at low pHs the repulsion among ionized chains is higher. CAM release rates have shown to be dependent on pH and on polymer proportion. At pH 1.2, the fastest profile was obtained when using high M.wt. CS. Drug diffusion was Fickian, so the process is governed by swelling/eroding. Whereas at pH 4.2, CAM release followed zero-order kinetics with no influence on M.wt. So, release is controlled by CAM low solubility.
Gómez-Burgaz
M
M
Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Madrid, Spain.
García-Ochoa
B
B
Torrado-Santiago
S
S
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002214:Capsules; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry*; D017291:Clarithromycin / Q000737:chemistry*; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005753:Gastric Mucosa / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013607:Tablets
D000900:Anti-Bacterial Agents; D002214:Capsules; D004337:Drug Carriers; D011108:Polymers; D013607:Tablets; D048271:Chitosan; D017291:Clarithromycin; D002266:Carboxymethylcellulose Sodium