Formulation and release characteristics of hydroxypropyl methylcellulose matrix tablet containing melatonin.
A hydroxypropyl methylcellulose (HPMC) matrix tablet containing melatonin (MT) was formulated as a function of HPMC viscosity, drug loading, type and amount of disintegrant, lubricant and glidant, and aqueous polymeric coating level and was compared with two commercial products. The release characteristics of the HPMC matrix tablet were investigated in the gastric fluid for 2 hr followed by study in intestinal fluid. The surface morphology of an uncoated HPMC matrix tablet using scanning electron microscopy (SEM) was crude, showing aggregated particles and rough crystals or pores, but it became smoother as the coating levels increased. As the HPMC polymer viscosity increased, the release rate had a tendency to decrease. As the drug loadings increased, the release rate slightly decreased. When Polyplasdone XL, Primojel, and Ac-Di-Sol, except Avicel, were incorporated in the HPMC matrix tablet, the release rate was markedly increased. There was no significant difference in release profiles when a mixture of lubricants and glidants (magnesium stearate, talc, and Cab-O-Sil), except for magnesium stearate alone, was incorporated into low and high viscosity grade HPMC matrix tablets. As the coating level increased, the release rate gradually decreased, giving an increased lag time. The sustained-release HPMC matrix tablet with optimizing formulations may provide an alternative for oral controlled delivery of MT and be helpful in the future treatment of circadian rhythmic disorders.
Lee
B J
BJ
Biological Rhythm and Controlled Release Laboratory, College of Pharmacy, Kangwon National University, Chuncheon, Korea. bjl@cc.kangwon.ac.kr
Ryu
S G
SG
Cui
J H
JH
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry; D008153:Lubrication; D008550:Melatonin / Q000737:chemistry / Q000493:pharmacokinetics*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010078:Oxazines; D011108:Polymers / Q000737:chemistry*; D013608:Tablets, Enteric-Coated; D014783:Viscosity
D003692:Delayed-Action Preparations; D010078:Oxazines; D011108:Polymers; D013608:Tablets, Enteric-Coated; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose; D008550:Melatonin