Periodontal disease is a prevalent inflammatory condition that affects the supporting structures of the teeth, leading to progressive tissue destruction and, if untreated, eventually tooth loss. The disease is primarily caused by pathogenic bacteria such as Porphyromonas gingivalis, which colonize periodontal pockets and trigger a chronic inflammatory response [1]. Conventional treatment strategies, including mechanical debridement and systemic antibiotics, often suffer from limitations such as low drug concentration at the target site, poor patient compliance, and the risk of antibiotic resistance [2]. To overcome these challenges, localized drug delivery systems, particularly in situ gels (ISGs), have gained increasing attention for periodontal therapy. ISGs are liquid formulations that undergo solvent exchange-induced phase inversion upon injection into an aqueous environment, forming a solid or semi-solid depot at the target site. This in situ transformation enables seamless adaptation to the target site's morphology, ensuring prolonged drug release, extended retention, and enhanced therapeutic efficacy, making ISGs an ideal approach for periodontal applications. Currently, ISG formulations have been explored in various biomedical applications, including cancer therapy, bacterial keratitis, osteoarthritis treatment, and oral cavity diseases. The viscosity and injection force of ISGs varied depending on the concentration of polymer and solvent type [3]. Chantadee et al. (2020) employed stearic acid and lauric acid as matrix formers, dissolved in biocompatible solvents including dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP), producing ISGs with low viscosity and excellent injectability, sustaining drug release [4].

The performance of ISGs is determined by the choice of matrix forming agents, solvent selection, and drug loading. To create an optimized ISG system with controlled drug release, easier injectability, and mechanical integrity, this study employs cellulose acetate butyrate (CAB) and palmitic acid (PAL) as matrix-forming agents, dissolved in the biocompatible solvents, DMSO and NMP. CAB, a hydrophobic, biocompatible polymer derived from cellulose, is soluble in most organic solvents but insoluble in water [5]. CAB is widely used in controlled-release drug delivery systems, including microcarriers [6], floating tablets [7], and matrix tablets [8]. The ability of CAB to form a dense and cohesive matrix in ISG formulations can significantly modulate solvent exchange and drug release kinetics [9,10]. On the other hand, PAL, a low-molecular-weight saturated fatty acid might enhance injectability by lowering formulation viscosity [11]. Moreover, PAL has been employed as a matrix-forming component in solvent exchange induced in situ forming matrix systems. For example, vancomycin-loaded PAL based ISG demonstrated rapid matrix solidification and significant crystallization capability, confirming its potential in forming dense matrices and modulating solvent exchange behavior [11]. DMSO and NMP have distinct solvent exchange behaviors and polarity profiles. They have unique properties in terms of polarity and miscibility with water [[12], [13], [14]]. Both DMSO and NMP have been employed in various localized and injectable drug delivery systems with acceptable biocompatibility when appropriately formulated. NMP serves as the solvent in Atridox®, an FDA-approved doxycycline-based ISG for periodontal therapy, confirming its clinical safety and local tolerability. Similarly, DMSO has been utilized as a solubilizing vehicle in in situ forming depots with low irritation potential at localized exposure sites [15,16]. In the present ISG system, rapid solvent exchange upon contact with the aqueous periodontal environment facilitates early diffusion away from tissues, while residual solvent is gradually released from the forming matrix. Given the small administration volume (≈50–100 μL; 30–60 mg solvent) [17], the actual exposure is minimal and unlikely to cause local or systemic toxicity. These precedents collectively support the suitability of both solvents for use in periodontal ISG applications. Moxifloxacin HCl (Mox), a fourth-generation broad-spectrum fluoroquinolone antibiotic, was selected as the active pharmaceutical ingredient in this study. Mox exhibits potent antimicrobial activity against Gram-positive and Gram-negative bacteria, including periodontal pathogens associated with both mild and severe periodontitis [18,19]. However, its short half-life and rapid clearance [20] necessitate a sustained-release delivery system to maintain therapeutic concentrations in periodontal pockets. The CAB/PAL-based ISG formulations were investigated aiming to diminish this limitation by providing extended drug release while maintaining optimal local drug concentrations at the infection site.

UV–Vis imaging is a powerful analytical technique that enables spatially and temporally resolved absorbance measurements, providing detailed insights into dynamic processes such as drug dissolution and solvent diffusion [21,22]. The core components of UV–Vis imaging systems include a pulsed xenon lamp or LEDs for illumination, possibly a band-pass filter for wavelength selection, and a special CMOS detector to capture absorbance images. UV–Vis imaging systems may operate in the 200–800 nm range, allowing the monitoring of various analytes, including drugs and excipients [21,23]. Compared to conventional dissolution or release testing methods, UV–Vis imaging offers the advantage of directly visualizing concentration (absorbance) changes over time, enabling the investigation of dynamic processes such as solvent transport, drug release, and matrix formation, without the need for sample extraction or external interference. Previous studies have demonstrated its utility in monitoring the behavior of in situ forming implants by capturing absorbance changes over time providing insights into the phase inversion kinetics and morphological transitions [[24], [25], [26]].

This study provides a novel combination of CAB and PAL as dual matrix-forming agents for solvent exchange–induced in situ forming gels. Unlike previous studies that primarily focused on single polymeric or fatty-acid systems, this work integrates sustained-release capability of CAB with the solvent exchange–facilitating property of PAL to achieve tunable release characteristics. Moreover, the application of UV–Vis imaging as a mechanistic tool offers a unique approach for visualizing and quantifying solvent transport, drug release, and phase inversion dynamics within CAB/PAL-based ISG systems.