Development of novel mucoadhesive pellets of metformin hydrochloride

Abstract

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.

Cefdinir Solid Dispersion Composed of Hydrophilic Polymers with Enhanced Solubility, Dissolution, and Bioavailability in Rats

“…Comparing the mucoadhesive properties of the polymers applied in this study, CMC-Na is known to have a higher degree of mucoadhesion than that of HPMC with the application for various formulations [ 19 , 20 , 21 ]. In contrast, PVP showed low or negligible mucoadhesive characteristics [ 22 ].…”

Preparation and <i>in Vitro</i> Drug Release Evaluation of Once-Daily Metformin Hydrochloride Sustained-Release Tablets

“…However, because of its relative low bioavailability (40% -60%) and short biological half-life (0.9 -2.6 h) [2][3][4][5], the immediate release dosage forms of MH such as conventional tablets and capsules, have to be administered three times a day [3], which results in a significant fluctuation in the plasma drug concentration and poor patient compliance. In order to overcome these problems, sustainedrelease drug delivery systems of MH including sustainedrelease matrix tablets [2,[6][7][8], sustained-release pellets [3,9], sustained-release microparticles [10], prolonged release microspheres [11], gastroretentive drug delivery preparation [12], pH-controlled peroral delivery formulation [13] have been developed in recent years. Though sustained release formulations of MH have been reported to prolong drug release, formulation and technologies used in these studies were complicated and costly, which influence industrial scale and market expansion.…”

The influence of AT1002 on the nasal absorption of molecular weight markers and therapeutic agents when co-administered with bioadhesive polymers and an AT1002 antagonist, AT1001

“…Among bioadhesive polymers tested, carrageenan and Na‐carboxymethyl cellulose (CMC) have been used to increase the membrane residence time of drugs. Carrageenan, an anionic polymer derived from seaweed, has a high solution viscosity and good bioadhesion, [25,26] and Na‐CMC has a high mucoadhesion formed by water uptake [27] …”

“…Carrageenan, an anionic polymer derived from seaweed, has a high solution viscosity and good bioadhesion, [25,26] and Na-CMC has a high mucoadhesion formed by water uptake. [27] For the inhibition study, the nasal membranes were pre-treated with AT1001, an octa-peptide inhibitor of paracellular permeability [28] and a zonulin binding antagonist. [20] AT-1001 inhibits gliadin-induced intestinal epithelial cells' cytoskeleton rearrangement, tight junction disassembly and peak F-actin increment.…”