Controlled release of dual drug-loaded hydroxypropyl methylcellulose matrix tablet using drug-containing polymeric coatings.
A dual drug-loaded hydroxypropylmethylcellulose (HPMC) matrix tablet simultaneously containing drug in inner tablet core and outer coated layer was formulated using drug-containing aqueous-based polymeric Eudragit RS30D dispersions. Effects of coating levels, drug loadings in outer layers, amount and type of five plasticizers and talc concentration on the release characteristics were evaluated on the characteristics in simulated gastric fluid for 2 h followed by a study in intestinal fluids. Melatonin (MT) was selected as a model drug. The surface morphology of dual drug-loaded HPMC tablets using scanning electron microscope (SEM) was smooth, showing the distinct coated layer with about 75-microm coating thickness at the 15% coating level. Unlike the uncoated and conventionally coated HPMC tablet, the dual drug-loaded HPMC matrix tablet gave a biphasic linear release, showing a zero-order for 4 h (first) followed by another zero-order release when fitted using linear regression (r(2) = 0.99). As the coating levels (15, 25%) increased, the release rate was further decreased. The biphasic release profiles of dual drug-loaded HPMC matrix tablet was unchanged except when 25% coating level containing 0.5% drug concentration was applied. As the drug concentration in polymeric coating dispersion increased (0.25-1.0%), the amount of drug released increased. The time for the first linear release was also advanced. However, the biphasic release pattern was not changed. The biphasic release profiles of dual drug-loaded HPMC matrix tablet were highly modified, depending on the amount and type of five plasticizers. Talc (10-30%) in coating dispersion as an anti-sticking material did not affect the release profiles. The current dual drug-loaded HPMC matrix tablet, showing biphasic release profiles may provide an alternative to deliver drugs with circadian rhythmic behaviors in the body but needs to be further validated in future in human studies. The dual drug-loaded coating method is also interesting for the modified release of poorly water-soluble drugs because solubilizers and other additives can be added in drug-containing polymeric coating dispersions.
Lee
B J
BJ
Biological Rhythm and Controlled Release Laboratory, College of Pharmacy, Kangwon National University, Chuncheon, South Korea. bjl@cc.kangwon.ac.kr
Ryu
S G
SG
Cui
J H
JH
D000927:Anticonvulsants / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry; D008550:Melatonin / Q000737:chemistry / Q000493:pharmacokinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010078:Oxazines; D010968:Plasticizers / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D013607:Tablets; D013608:Tablets, Enteric-Coated; D013627:Talc / Q000737:chemistry
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D010078:Oxazines; D010968:Plasticizers; D011108:Polymers; D013607:Tablets; D013608:Tablets, Enteric-Coated; D013627:Talc; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose; D008550:Melatonin