Novel pH-sensitive gum ghatti-cl-poly(acrylic acid) composite hydrogel based on graphene oxide for metformin hydrochloride and sodium diclofenac combined drug-delivery systems†

The objective of the present study was to synthesize pH-sensitive gum ghatti-cl-poly (acrylic acid)/GO hydrogels for the drug delivery and controlled combined release of metformin hydrochloride and sodium diclofenac. Gum ghatti (Gg) and acrylic acid (AA) were free radicals copolymerized using N,N‘-methylenebisacrylamide (MBA) and tetramethyl ethylenediamine as cross-linkers and ammonium persulfate (APS) as an initiator. The structure and surface morphology of the composite hydrogel were determined using FTIR and SEM analyses, respectively. The FTIR studies confirmed the successful acrylic acid and graphene oxide grafting and drug binding onto the backbone of the synthesized hydrogel. Drug-release kinetics and mechanisms were investigated using zero- and first-order kinetic models as well as the Korsmeyer–Peppas model, Higuchi model, and Hixson–Crowell model. Drug-release experiments revealed the important characteristics related with physiologically expected pH levels, including a high release rate at pH 9.2. At pH 9.2, metformin HCl drug release increased from 4.68% to 37.46%, whereas sodium diclofenac release increased from 3.25% to 54.75%. However, at pH 9.2, both metformin hydrochloride and sodium diclofenac showed non-Fickian transport mechanisms. In summary, combining drugs may reduce the efficacy of a single medication while influencing metabolic rescue mechanisms.