Development of novel mucoadhesive pellets of metformin hydrochloride.
Mucoadhesive polymer-coated pellets containing metformin hydrochloride were prepared by the powder-layering technique using a centrifugal fluidizing (CF)-granulator. Four high-viscosity polymers were applied to make the pellets: 1) hydroxymethylcellulose (HPMC), 2) sodium alginate (Na-Alg), 3) HPMC/Carbopol, and 4) sodium carboxylmethylcellulose (Na-CMC). The physical crushing test, mucoadhesive test, zeta-potential test, in vitro release study and observation of gastroretention state of the dosage form were performed to investigate the pellets. The strong adhesive interaction between the Na-CMC-coated pellets and the mucin disc was obtained by mucoadhesive test. Na-Alg was most effective among the polymers used in changing the value of zeta potential of the mucin solution by the interaction between a polymer and a mucin particle. Results from drug dissolution study showed that over 95% of the drug from all the four pellets was released before 2 h, while Na-CMC- and Na-Alg-coated pellets showed a moderate sustained-release in SGF (simulated gastric fluid) and SIF (simulated intestine fluid), respectively. In conclusion, Na-CMC and Na-Alg seem to be promising candidates for mucoadhesive formulation and further studies to improve the sustained-release property are underway for achieving the ultimate goal of once-a-day formulation of metformin hydrochloride.
Piao
Jingshu
J
Sookmyung Women's University, Seoul, 140-742, Korea.
Lee
Ji-Eun
JE
Weon
Kwon-Yeon
KY
Kim
Dong-Wook
DW
Lee
Jung Suk
JS
Park
James D S
JD
Nishiyama
Yuichi
Y
Fukui
Ikuo
I
Kim
Jin-Seok
JS
D000180:Acrylic Resins; D000268:Adhesiveness; D000464:Alginates / Q000737:chemistry; D000818:Animals; D002214:Capsules; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005753:Gastric Mucosa / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006244:Hardness; D006603:Hexuronic Acids / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000378:metabolism; D065347:Hypromellose Derivatives; D007700:Kinetics; D008687:Metformin / Q000737:chemistry* / Q000378:metabolism; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D009077:Mucins / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry; D011208:Powders; D051381:Rats; D012995:Solubility; D014783:Viscosity
D000180:Acrylic Resins; D000464:Alginates; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006603:Hexuronic Acids; D007004:Hypoglycemic Agents; D009077:Mucins; D011108:Polymers; D011145:Polyvinyls; D011208:Powders; C006912:carboxypolymethylene; D065347:Hypromellose Derivatives; D020723:Glucuronic Acid; D008747:Methylcellulose; D008687:Metformin; D002266:Carboxymethylcellulose Sodium