Stomach-Specific Drug Delivery of Clarithromycin Using aSemi Interpenetrating Polymeric Network Hydrogel Made ofMontmorillonite and Chitosan: Synthesis, Characterization and InVitro Drug Release Study

Abstract

Purpose: In this study, we aimed to prepare an extended drug delivery formulation ofclarithromycin (CAM) based on a semi-interpenetrating polymer network (semi-IPN) hydrogel.Methods: Synthesis of semi-IPN hydrogel nanocomposite made of chitosan (CS), acrylicacid (AA), acrylamide (AAm), polyvinylpyrrolidone (PVP), and montmorillonite (MMT) wasperformed by free radical graft copolymerization method. Swelling kinetic studies were done inacidic buffer solutions of hydrochloric acid (pH = 1.2), acetate (pH = 4), and also distilled water.Also, the effects of MMT on the swelling kinetic, thermal stability, and mechanical strengthof the hydrogels were evaluated. Moreover, in vitro release behavior of CAM and its releasekinetics from hydrogels were studied in a hydrochloric acid buffer solution.Results: Fourier transform infrared spectroscopy (FTIR) results revealed that synthesis of semi-IPN superabsorbent nanocomposite and CAM incorporation into hydrogel was performed,successfully. Introducing MMT into hydrogel network not only improved its thermal stabilitybut also increased mechanical strength of the final hydrogel product. Also, in comparisonwith neat hydrogel (1270 g/g), hydrogel nanocomposite containing 13 wt% MMT exhibitedgreater equilibrium swelling capacity (1568 g/g) with lower swelling rate. In vitro drug releaseexperiments showed that CS-g-poly(AA-co-AAm)/PVP/MMT/CAM formulation possesses asustained release character over extended period of time compared with CS-g-poly(AA-co-AAm)/PVP/CAM formulation.Conclusion: In the presence of MMT, the effective life time of drug is prolonged, demonstrating asustained release property. The reason is that interlinked porous channels within superabsorbentnanocomposite network hinder penetration of aqueous solutions into hydrogel and subsequentlycause a slower drug release.

Study of Different Chitosan/Sodium Carboxymethyl Cellulose Proportions in the Development of Polyelectrolyte Complexes for the Sustained Release of Clarithromycin from Matrix Tablets

“…Previous studies indicated that the highest solubility values of CL are obtained at a pH lower than 3.0 [ 15 ]. For this reason, we selected CS/CMC complexes with high CS ratios for dissolution studies in 0.1 N HCl, namely CL:(CS) 80:(20), CL:(CS:CMC) 40:(54:6), and 40:(30:30).…”

“…The solubility of CL increases as the pH of the dissolution medium decreases. CL is also unstable in an acidic medium (pH 1–2) but stable at a pH above 4 [ 15 ]. The use of omeprazole with CL PECs allows for sustained release systems that maintain high levels of CL in the gastric environment [ 12 , 15 ].…”

“…The presence of (COO − ) groups, such as in CL, and their pKa favor their inclusion in CS/CMC interpolymeric complexes at a pH close to 4.0 [ 15 ]. The use of different kinetic models may be important for understanding drug release from PECs [ 16 , 17 ].…”

Recent developments in the use of organic–inorganic nanohybrids for drug delivery

“…Among these mechanisms, ion exchange takes a prominent place (Rajkumar, Kevadiya, & Bajaj, ). In fact, this mechanism along with the remarkable swelling capability (Panahi, Gharekhani, Hamishehkar, Zakeri‐milani, & Gharekhani, ) and adsorptivity (Joshi, Kevadiya, Mody, & Bajaj, ) of clay minerals have paved the basis for extensive use of clay‐based hybrid materials to be explored for their potential use in extended release systems (Jain & Datta, ), site‐specific release systems (Mahkam, Rafi, & Gheshlaghi, ), and drug solubility improvement systems (Zheng, Luan, Wang, Xi, & Yao, ). Enhanced properties such as increased surface area, porosity, and ion exchange capacity may improve clay–drug affinity, and enable extended release of drugs (Bello, Junior, Vieira, Dias, & De, ).…”

Fabrication and characterization of a novel semi-interpenetrating network hydrogel based on sodium carboxymethyl cellulose and poly(methacrylic acid) for oral insulin delivery

“…[13][14][15] The pH-sensitive hydrogels have been widely used for a controlled and site-specific delivery of bioactive proteins or peptides because they are able to respond to the pH change of biological fluids. 16,17 Various hydrogels based on biocompatible polymers containing carboxylic acid groups such as poly(acrylic acid) (PAA) and poly(methylacrylic acid) (PMAA) have been developed. These polymers have shown the potential ability in opening epithelial tight junctions, which is favorable for the absorption of insulin.…”