Water Tolerance and Matrix Morphology of Aqueous-induced Borneol-based In Situ Matrix Formation for Periodontal Pocket Delivery

Abstract

In situ forming matrix systems (ISMs) have gained increasing attention for localized drug delivery, particularly for periodontal pocket treatment through injection. Crevicular fluid exposure can induce a phase transformation of the ISM from a solution into a matrix. Organic solvents, including ethanol, N-methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), and 2-pyrrolidone, are typically used in ISM formulations due to their water miscibility and biocompatibility. In this study, 40% borneol solutions in these solvents were used as the matrix former. The water tolerance, defined as the minimum amount of water needed to induce phase inversion from a solution into a matrix, was investigated employing an aqueous titration technique. The water tolerance levels for borneol were 39.65%, 14.77%, 7.40%, and 6.71% v/v in ethanol, NMP, DMSO, and 2-pyrrolidone, respectively. Borneol in DMSO demonstrated low water tolerance and low viscosity (5.61 ± 0.12 cPs), which facilitates rapid matrix formation and ease of administration into the periodontal pocket. Thus, DMSO was considered a suitable solvent for borneol-based ISM. Further, the morphology of the borneol crystal matrix was evaluated under an inverted stereomicroscope at various borneol concentrations (10%–60%). Formulations with lower borneol concentrations required more time to crystallize than those with higher concentrations. The resulting crystal matrix entrapped the drug, thereby retarding its release. The choice of solvent and borneol concentration significantly affected the matrix formation rate and morphology. Therefore, the appropriate selection of solvent and borneol concentration is crucial for developing an aqueous-induced borneol-based ISM for periodontitis treatment.