The Effects of Synthetic Polymers on the Release Patterns of Bupivacaine Hydrochloride from Sodium Hyaluronate Hydrogels

Abstract

Background: Using hydrogels for the controlled release of drugs is beneficial for patients, who then receive the proper dose of the medicinal substance. In addition, the formulation can provide more consistent drug absorption while reducing the frequency of dosing. Objectives: The aim of this investigation is to propose a novel HA (sodium hyaluronate)-based hydrogel for intra-articular injection doped with synthetic polymers and incorporated with bupivacaine hydrochloride (Bu) as a local anesthetic. The other aim of this study is to reveal the effects of the formulation’s ingredients on its viscosity and the relationship between the hydrogel’s viscosity and drug release. Methods: First, HA-based hydrogels doped with synthetic polymers and incorporated with Bu were prepared. A study of the hydrogels’ viscosities was performed using a rotational viscometer. Release tests were carried out by employing a paddle-over-disk apparatus following the USP/Ph.Eur guidelines. The drug concentrations in the acceptor fluid were analyzed spectrophotometrically. Results: It was found that the viscosity of the hydrogels doped with synthetic polymers was higher than the viscosity of the hydrogels made with only HA. The viscosity of the hydrogels doped with AX (ammonium acryloyldimethyltaurate/VP copolymer) was the highest, measuring 6750 ± 160 cP and 12623 ± 379 cP with and without Bu, respectively. The results of the kinetic experiment indicate that the Higuchi and Korsmeyer–Peppas models best described the drug release. Bu was released the most slowly from the formulation doped with AX. The release rate constants obtained from the Higuchi and Korsmeyer–Peppas models were kH = 4.4 ± 0.2 mg × min−1/2 and kK-P = 3.4 ± 0.2 × 10−2 min–N, respectively. The half-release time, calculated using the Higuchi model, was the longest for the formulation doped with AX, at 199.5 ± 17.6 min. Conclusions: This indicates that the incorporation of AX into the hydrogel may prolong the drug dissolution. The hydrogel doped with AX was the optimal formulation for the controlled release of Bu.