Long-Lasting In Situ Forming Implant Loaded with Bupivacaine: Investigation on Polymeric and Non-Polymeric Carrier and Solvent Effect

Abstract

Introduction: Typically, in situ forming implants utilize Poly (lactide-co-glycolide) (PLGA) as a carrier and N-methyl-2-pyrrolidone (NMP) as a solvent. However, it is essential to develop different carriers to release various drugs in a controlled and sustained manner with economic and safety considerations. Objective: The present study aims to evaluate the in-vitro release of Bupivacaine HCl from in situ forming systems as post-operative local anesthesia. Methods: We used Sucrose acetate isobutyrate (SAIB), PLGA 50:50, and a mixture of them as carriers to compare the release behavior. Besides, the effect of PLGA molecular weight (RG 502H, RG 503H, and RG 504H), solvent type, and solvent concentration on the drug release profile was evaluated. The formulations were characterized by investigating their in-vitro drug release, rheological properties, solubility, and DSC, in addition to their morphological properties. Furthermore, the Korsmeyer-Peppas and Weibull models were applied to the experimental data. The results revealed that a mixture of SAIB and PLGA compared to using them solely can extend the Bupivacaine HCl release from 3 days to two weeks. Results: The DSC results demonstrated the compatibility of the mixture by showing a single Tg. The formulation with NMP had a higher burst release and final release in comparison with other solvents by 30% and 96%, respectively. Increasing the solvent concentration from 12% to 32% raised the drug release significantly, which confirmed the larger porosity in the morphology results. From the Korsmeyer-Peppas model, the mechanism of drug release is predicted to be non-Fickian diffusion.

Crystallization of ropivacaine and bupivacaine when mixed with different adjuvants: a semiquantitative light microscopy analysis

“…Strengths of this study include the focus on LA-adjuvant combinations that are commonly used in clinical anesthesia practice for central and peripheral nerve blocks, in contrast to earlier studies 7–13 20. Earlier studies are frequently burdened by impractical mixing ratios (1:1 ratio of LA with adjuvants) and/or unrealistically long storage times.…”

“…Earlier studies are frequently burdened by impractical mixing ratios (1:1 ratio of LA with adjuvants) and/or unrealistically long storage times. Moreover, studies focusing on pH compatibility frequently use different endpoints and methodologies (gas chromatography/mass spectroscopy, high pressure liquid chromatography, concentration assays), the clinical implications of which may differ from our findings 12. We chose a semiquantative approach to detect the presence of crystals as an analytical correlate to precipitation.…”

“…However, little is known about the pH dependency, magnitude, or timing of crystal precipitation effects for various LA adjuvant combinations. Existing studies are limited by examining impractical concentrations of LAs, storage times which are unrealistically long in clinical practice, adjuvants that are not used clinically, or by their focus on neurotoxicity 7–13…”

Novel CO2-encapsulated Pluronic F127 hydrogel for the treatment of Achilles tendon injury

“…Figure 3 B illustrates the DSC thermograms of the pristine hydrogel, bupivacaine, and B-hydrogel. The exothermal peak of the pristine hydrogel at 55.7 °C and of bupivacaine at 92.2 °C could be identified in the B-hydrogel 43 , 44 . The results of these analyses indicate that the hydrogels effectively contained the drugs.…”