Solvent exchange-induced in situ gels (ISGs) composed of cellulose acetate butyrate (CAB) and palmitic acid (PAL) as matrix forming agents were developed by dissolving in dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP) for localized moxifloxacin HCl (Mox) delivery in periodontal treatment. The formulations were characterized in terms of viscosity, injectability, mechanical properties, matrix formation, drug release, and antimicrobial activity. UV-Vis imaging was employed to investigate the dynamic processes of solvent transport, drug release, and matrix formation. Combination of CAB and PAL provided acceptable injectability and prolonged drug release. Phase inversion dynamics via UV-vis imaging showed that DMSO based formulations exhibited faster solvent exchange as well as faster drug diffusion as compared to NMP based formulations, which exhibited slower solvent diffusion, leading to more sustained drug release and aligned with matrix formation. Mox-loaded combined CAB and PAL-based ISG demonstrated notable antimicrobial activity against Staphylococcus aureus, Candida albicans, and Porphyromonas gingivalis associated with periodontitis, confirming their potential for periodontitis therapy. This study highlights the critical role of matrix composition, solvent selection, and phase inversion in influencing mechanistic drug release from CAB-PAL ISG for targeted periodontitis therapy as demonstrated through UV-Vis imaging.

"Ya-Pai," a traditional Thai powdered medicine applied as an oral paint, presents application challenges and has seen limited formulation development. This study aims to modernize Ya-Pai by developing it into an advanced dosage form, an in situ forming system, for the treatment of oropharyngeal candidiasis (OPC). Clotrimazole-embedded in situ forming paints (ISPs) were developed using lauric acid and palmitic acid as ISP formers for the treatment of OPC. Their formation of matrix layer, transformation at interface, buccal mucosa permeation, and antifungal activities investigated to prove the concept. The formulation with a high concentration of ISP former (F2) demonstrated superior matrix formation and a rapid transition at the interface within 0.5 minutes, along with slower matrix growth compared to other formulations (5 minutes). In contrast, the formulation with a low concentration of ISP former (F1) exhibited faster drug permeation through the buccal mucosa and a lower percentage of drug remaining in the buccal mucosa (28.64 +/- 2.80 % and 20.27 +/- 1.27 % for F2 and F1, respectively). The drug permeation rates of F1 and F2 were 4.0363%/hour(1/2) and 3.492%/hour1/2, respectively, following Higuchi's model. The antifungal test using the agar diffusion method demonstrated that the prepared ISPs effectively inhibited the growth of Candida albicans (32.3 +/- 0.6 and 29.3 +/- 1.2 mm for F1 and F2, respectively) and others. Thereby, the developed clotrimazole-embedded ISP shows a promising concept as a modernized Ya-Pai for the OPC treatment. However, further study such as in vivo efficacy, mucosal safety, and pharmacokinetic evaluation should be conducted.

The modulation of phase inversion dynamics and molecular transport is critical for optimizing in situ forming matrix (ISM) systems. This study elucidates the distinct roles of borneol and triacetin in tailoring the physicochemical properties of a borneol-based ISM for buccal delivery. Using real-time interfacial microscopy and confocal laser scanning microscopy (CLSM), the solvent exchange mechanisms and matrix evolution were characterized. Results demonstrated that triacetin concentration is a critical determinant of matrix density structure. Conversely, borneol functioned as a dual-action agent, accelerating phase inversion while simultaneously enhancing mucosal permeability. Comparative diffusion studies using hydrophilic sodium fluorescein (SF) and lipophilic Nile red (NR) revealed that molecular release was governed by viscosity- and polarity-dependent diffusion controls. Kinetics analysis indicated non-Fickian release for SF, whereas NR diffusion was partition-limited due to hydrophobic affinity. Ultimately, the interplay between the permeation-enhancing effects of borneol and the release-retarding capacity of triacetin offers a tunable platform for designing precise, controlled-release intraoral delivery systems.

This study aimed to develop a solvent removal-based in situ forming gel (ISG) loaded with salicylic acid (SAL) using myristic acid (MYR) as a matrix-forming agent. SAL-loaded MYR-based ISGs were prepared using N-methyl-2-pyrrolidone (NMP) or dimethyl sulfoxide (DMSO) as solvents and evaluated for physicochemical properties, matrix formation behavior, mechanical characteristics, and in vitro drug release. Increasing MYR content influenced viscosity, gel formation kinetics, and depot integrity, resulting in prolonged SAL release of up to 20 days in DMSO-based formulations. The release kinetics were best described by the Peppas-Sahlin model, indicating diffusion-dominated drug transport. The selected formulation containing 30% w/w SAL and 20% w/w MYR exhibited acceptable injectability, reproducible in situ matrix formation, and sustained drug retention. Antimicrobial testing confirmed that SAL retained biological activity against oral pathogens following incorporation into the ISG system, although solvent contributions to antimicrobial effects were also observed. These findings demonstrate the feasibility of a MYR-based ISG system in which SAL contributes to both therapeutic activity and matrix formation, supporting its potential for localized oral drug delivery.

Background:Gentian violet (GV) is a broad-spectrum antimicrobial agent with documented efficacy against oropharyngeal candidiasis and periodontal pathogens, but its clinical use is limited by poor local retention. In situ forming matrices (ISMs) offer a promising strategy for sustained, localized drug delivery. Objectives:This study aimed to develop and evaluate GV-loaded ISMs using ibuprofen (IBU) and palmitic acid (PA) as dual-function matrix-forming agents in DMSO and NMP solvents for the localized treatment of oropharyngeal candidiasis and periodontitis. Methods:ISM formulations were prepared by simple mixing and characterized for viscosity, rheological behavior, injectability, mechanical properties, and in situ matrix formation. In vitro drug release of GV and IBU was quantified by a validated simultaneous HPLC method using an ACE C18 column with UV detection at 590 and 222 nm, respectively. Drug-release kinetics were modeled using zero-order, first-order, Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin models. Antimicrobial activity against Staphylococcus aureus, Candida albicans, C. tropicalis, and Porphyromonas gingivalis was assessed by agar diffusion over 15 days. Molecular interactions were investigated using density functional theory (DFT) calculations at the B3LYP-D3BJ/6-31G(d,p) level. Results:All formulations showed Newtonian-flow behavior and acceptable injectability (0.78-1.50 N). GV and IBU release followed the Peppas-Sahlin model, with NMP-based systems releasing GV and IBU faster due to more porous matrix architecture, while DMSO-based systems formed denser matrices with slower release. All GV-containing formulations maintained antimicrobial inhibition zones for up to 15 days. DFT calculations revealed strong GV-IBU (-1.63 eV) and GV-PA (-1.53 eV) binding energies, supporting sustained drug entrapment. Conclusions:GV-loaded IBU/PA-based ISMs demonstrate sustained antimicrobial efficacy for up to 15 days with solvent-dependent release behavior. These systems show potential as localized, single-injection therapies for oral infections. Stability evaluation and in vivo biocompatibility studies are identified as necessary future steps.

This study reports the development and multiscale evaluation of a nitrocellulose (Nc)-based in situ gel (ISG) system for localized delivery of moxifloxacin HCl (Mx) in periodontitis therapy. The formulations, composed of 15

Effervescent matrix tablets offer a dynamic platform for controlling drug release by modulating water sorption, swelling, and matrix disintegration. This study presents a mechanistic and numerical framework to investigate the release kinetics of ibuprofen from hydroxypropyl methylcellulose (HPMC)-based matrices containing varying concentrations of effervescent agents. Under simulated gastric conditions (0.1 N HCl, pH 1.2), increased effervescence significantly enhanced water sorption and matrix porosity, accelerating drug release. To capture these effects quantitatively, a diffusion-based model was developed using Fick's second law in cylindrical coordinates, integrated with free volume theory to account for water-dependent diffusivity. A finite difference approach, coupled with Gauss-Newton optimization, was employed to estimate key diffusivity parameters with high precision. The model accurately reproduced experimental release profiles (R-2 > 0.99) and revealed how effervescence and HPMC content synergistically regulate swelling behavior and diffusivity. Estimated water diffusion coefficients ranged from 5.23 x 10(-4) to 136.93 x 10(-4) cm(2)/min across formulations, highlighting formulation-dependent mass transport dynamics. These findings highlight the value of integrated computational and experimental approaches for guiding the rational design of effervescent-based controlled release systems and advance our understanding of formulation-structure-function relationships in oral drug delivery.

UV-Visible (UV-Vis) imaging provides real-time and spatially resolved insights into drug transport, solvent diffusion, and matrix formation, making it a useful tool for evaluating in situ forming matrices (ISMs). ISMs are injectable liquids that solidify upon contact with aqueous environments to sustain drug release. Borneol, a poorly water-soluble and biocompatible monoterpene alcohol, was selected as the matrix former, with triacetin as a hydrophobic co-solvent to modulate drug release in a concentration-dependent manner. This study investigated the effects of borneol matrix and triacetin concentration on solvent exchange, matrix structure, and drug transport in borneol-based ISMs. Formulations containing borneol (40 % w/w), doxycycline hyclate (0.5 % w/ w), and triacetin (0-25 % w/w) in N-methyl-2-pyrrolidone (NMP) were characterized by microscopy and UV-Vis imaging to evaluate morphology, solvent diffusion, and drug release. The results showed that borneol matrices effectively restricted solvent and drug transport. Incorporation of 5 % w/w triacetin had a negligible effect on initial solvent exchange and drug release, whereas 25 % w/w triacetin disrupted matrix integrity, resulting in accelerated solvent exchange and unrestricted Dox diffusion. A strong linear correlation between drug and solvent diffusion was observed, with the borneol matrix promoting more efficient drug transport under equivalent solvent diffusion conditions compared to the non-matrix system. Overall, UV-Vis imaging provided realtime insights into solvent exchange mechanisms, matrix formation, and drug release behavior in ISM, confirming that borneol matrices with 5 % w/w triacetin loading can prolong drug release.

The periodontitis leads to the formation of periodontal pockets, which provide an ideal site for localized antimicrobial drug delivery for therapy. In this study, metronidazole (Met)-loaded in-situ matrix (ISM) systems were developed to assess their physical and drug release characteristics. Bleached shellac (BS) and fatty compounds such as beeswax, carnauba wax, candelilla wax, shellac wax, and stearic acid (SA) were tested as matrix-forming agents. ISM systems containing BS and SA in BS ratios of 2:1, 1:1, and 1:2 at 30% w/w were chosen because they resulted in clear, liquid-like ISMs. Increasing the BS content raised both the density and viscosity of the ISM. Upon injection into simulated crevicular fluid these liquid ISMs quickly formed solid matrices. Drug release was notably prolonged, with only around 6% released within the first day and sustained over six days. Met-loaded BS-SA ISM shows promise as a delivery system for intra-periodontal pocket route. However, further studies should focus on modulating release profile to improve drug delivery.

Curcumin, the important active component in turmeric extracts, has gained significant attention demonstrating notable effectiveness across a wide range of human pathological conditions. This study explores the development and characterization of borneol and ibuprofen-based in situ implant (ISI) systems loaded with curcumin, designed for advanced therapeutic applications. Curcumin ISI solution enabled self-transformation into matrix at 40% w/w concentration. Ibuprofen and borneol enhanced curcumin transformation at lower concentration. These ISI systems exhibited low viscosity and swift transformation aiding for their administration by injection. Macroscopic and crosssectional imaging provided insights into their phase inversion process. Curcumin-loaded borneolbased ISI demonstrated high antioxidant activity. Both curcumin-loaded borneol-based and ibuprofen-based ISIs showed efficient antimicrobial activities against related periodontitis pathogens. These findings underscore the potential of curcumin-loaded borneol and ibuprofen-based ISI systems as promising candidates for localized drug delivery, particularly in treating periodontitis.

In situ gels (ISGs) are well-known as smart drug delivery systems due to their inherent gel-forming ability and controlled drug release properties. This study presents comprehensive molecular-level insights into the physical properties and phase transformation processes of the formulation of 10 to 60% w/w myristic acid (MYR)-based ISGs using ethanol (EtOH), N-methyl-2-pyrrolidone (NMP), and dimethyl sulfoxide (DMSO) as solvents, investigated using conventional experimental techniques, molecular dynamics (MD) simulations, and density functional theory (DFT). The results showed that 40% w/w myristic acid in NMP (NM40) exhibited swift gel formation with low water tolerance to induce phase inversion into the matrix. Scanning electron microscopy revealed that NM40 had multilayer, sheet-like structures, in which NM40 displayed a denser and less porous topography than 40% w/w myristic acid in DMSO (DM40). NM40 also had efficient antimicrobial efficacy against various microbes; thus, NM40 was the appropriate ISG as an antimicrobial drug delivery system. Moreover, MD simulation demonstrated that during the initial stage of gel formation, MYR began to agglomerate and arrange in an orderly manner, resembling crystallization. A higher concentration of MYR promoted a higher compactness of the MYR structure and the lower solvent exchange rate. Additionally, DFT calculations demonstrate that hydrogen bonding is the key interaction, contributing to the orderly arrangement of molecules. These significant findings pave the way for the tailoring and optimization of ISG formulations in drug delivery systems.

Lac dye and D&C red No. 27, natural and synthetic dye, are commonly used in pharmaceuticals and cosmetics. Their antioxidant, anti-inflammatory, and antimicrobial activities were investigated using the DPPH, the thermal inhibition of egg albumin protein denaturation and the agar diffusion methods, respectively. Lac dye demonstrated stronger antioxidant activity than ascorbic acid (the positive control) and D&C red No. 27, with EC50 values of 2.03 +/- 0.08, 8.28 +/- 0.02, and 397.87 +/- 1.16 mu g/ml, respectively. D&C red No. 27 exhibited anti-inflammatory activity (EC50 value 114.61 +/- 8.46 mu g/ml) higher than diclofenac sodium (EC50 754.11 +/- 1.42 mu g/ml), whereas lac dye induced inflammation with an IC50 value of 136.40 +/- 2.31 mu g/ml. At a concentration of 0.25% w/v, lac dye effectively inhibited the growth of Staphylococcus aureus, Escherichia coli, and Porphyromonas gingivalis, producing clear inhibition zones of 17.7 +/- 0.6, 18.3 +/- 0.6, and 24.3 +/- 0.6 mm, respectively. However, lac dye displayed antifungal activity against Candida albicans and Candida tropicalis compared to the solvent (PEG 400) at a concentration of 2% w/v. D&C red No. 27 inhibited against S. aureus, E. coli, and P. gingivalis, with clear zones of 15.3 +/- 0.6, 15.3 +/- 0.6, and 22.3 +/- 0.6 mm, respectively, at a concentration of 0.25%. Notably, D&C red No. 27 demonstrated strong antimicrobial activity against Propionibacterium acnes, with an inhibition zone of 41.0 +/- 1.0 mm, which surpassed the 24.0 +/- 1.7 mm zone produced by lac dye at the same concentration of 0.25% w/v. However, D&C red No. 27 exhibited only a limited ability to inhibit both types of fungi. These findings suggest that both dyes may offer valuable benefits for the development of future formulation.

Cellulose acetate butyrate (CAB) and cellulose acetate propionate (CAP) are biobased materials that are insoluble in water and present a potential alternative to fossil-based plastics. Solvent removal-induced in situ matrices are gaining attention as an innovative dosage form for localized drug delivery for periodontitis therapy. This study aims to develop levofloxacin hemihydrate (Lh)-loaded in situ matrices formed through solvent removal, incorporating various molecular weights (MWs) and concentrations of CAB and CAP. Increased MWs and higher concentrations of these cellulosic esters significantly improved formulation viscosity and injection force, contributing to enhanced phase inversion and greater matrix toughness. Microscopic analysis of interfacial phase changes revealed progressive thickening of the matrix over time, which was influenced by polymer concentration and limited solvent movement. The transformed matrices with high MW CAP and elevated CAB content demonstrated prolonged drug release, predominantly following first-order kinetics, suggesting drug dissolution and diffusion through the scaffold structure. CAB-based in situ matrices containing 15% and 20% polymer exhibited low viscosities suitable for injection, along with optimal gel formation for maintaining their shape, and adhered effectively to periodontal pockets. These matrices provided extended Lh release for up to 120 h and inhibited the growth of periodontopathic bacteria for over 15 days. Therefore, the developed Lh-loaded in situ matrices show promise as an effective treatment for periodontitis, warranting further research to explore their therapeutic potential.

Solvent-exchange-induced in situ forming gel (ISG) refers to a drug delivery system that transforms from a solution state into a gel or solid matrix upon administration into the body and exposure to physiological aqueous fluid. This study investigates the molecular behavior and phase inversion process of cellulose acetate butyrate (CAB)-based in situ forming gel (ISG) formulations containing moxifloxacin (Mx) or benzydamine HCl (Bz) as model drugs dissolved in N-methyl pyrrolidone (NMP) using molecular dynamics (MD) simulations and density functional theory (DFT) calculations. The simulations reveal a solvent exchange mechanism, where the diffusion of water molecules replaces NMP, driving the formation of the CAB matrix. Bz exhibited faster diffusion and a more uniform distribution compared to Mx, which aggregated into clusters due to its larger molecular size. The analysis of the root mean square deviation (RMSD) and radius of gyration confirmed the faster diffusion of Bz, which adopted a more extended conformation, while Mx remained compact. The phase transformation was driven by the disruption of CAB-NMP hydrogen bonds, while CAB–water interactions remained limited, suggesting that CAB does not dissolve in water, facilitating matrix formation. The molecular configuration revealed that drug–CAB interactions were primarily governed by hydrophobic forces and van der Waals interactions rather than hydrogen bonding, controlling the release mechanism of both compounds. DFT calculations and electrostatic potential (ESP) maps illustrated that the acetyl group of CAB played a key role in drug–polymer interactions and that differences in CAB substitution degrees influenced the stability of drug-CAB complexes. Formation energy calculations indicated that Mx-CAB complexes were more stable than Bz-CAB complexes, resulting in a more prolonged release of Mx compared to Bz. Overall, this study provides valuable insights into the molecular behavior of CAB-based Mx-, Bz-ISG formulations.

This study develops in situ forming gels (ISGs) incorporating cellulose acetate butyrate (CAB) and palmitic acid (PAL) as matrix-forming agents for localized periodontal drug delivery. The aim is to investigate the effects of CAB, PAL, and their combination on viscosity, rheological behavior, matrix formation, drug release, structural properties, and antimicrobial efficacy of moxifloxacin (Mx)-loaded ISGs. Drug release was examined, and release kinetics were determined using mathematical modeling. Scanning electron microscopy (SEM) and X-ray tomographic microscopy (XTM) were used to characterize matrix structures. Antimicrobial activity was assessed against Staphylococcus aureus, Candida albicans, and Porphyromonas gingivalis over 14 days using an agar diffusion assay. CAB dominant ISGs formed dense, slow-releasing matrices, while PAL dominant ISGs exhibited rapid phase inversion due to swift solvent exchange and higher porosity. NMP-based ISGs formed more porous matrices than DMSO-based ISGs in PAL-dominant formulations, enhancing drug diffusion at later stages. CAB/PAL combination ISGs balanced injectability, phase inversion, and prolonged drug release. Antimicrobial studies also confirmed sustained activity, with CAB dominant formulations maintaining efficacy for 14 days. CAB/PAL-based ISGs offer a promising strategy for sustained periodontal drug delivery while solvent selection modulates porosity and antimicrobial activity. This system demonstrates potential for prolonged therapeutic efficacy in localized periodontal treatment.

Typically, solvent removal-induced in-situ implants start in a solution state and undergo phase inversion to form depot formulations. In this research, the development and evaluation of a bioplastic in-situ implant for antibiotic drug loading were conducted. Two types of cellulose acetate butyrate (CAB) and cellulose acetate propionate (CAP) were used as bioplastic polymers for the in-situ implant. These polymers, at a concentration of 15% w/w, were dissolved in various solvents, including dimethyl sulfoxide (DMSO), glycerol formal (GF), N-methyl pyrrolidone (NMP), 2-pyrrolidone (PYR), and tetraglycol (TG). The polymers did not completely dissolve in TG, whereas all the other solvents were able to dissolve the polymers fully. Notably, the lowest apparent viscosity of these polymeric solutions was achieved when NMP was used as the solvent. The in-situ implants loaded with 1% w/w levofloxacin hemihydrate (Lv) were prepared using these polymers dissolved in NMP. The low viscosity of these solutions, combined with their rapid transformation into a depot matrix, facilitates administration via injection. The use of CAP as a polymer in this drug delivery system enabled self-transformation into a matrix in an aqueous medium due to solvent removal. Nonetheless, its depot hardness and adhesion were slightly lower than some in-situ implant prepared from CAB. Microscopic observations under both stereoscope and microscope confirmed swift phase inversion into a matrix implant of the Lv-loaded CAP-based in-situ implant after exposure to aqueous phase of agarose gel. This implant prolonged the release of the antibiotic drug for five days. Additionally, the developed in-situ implant demonstrated effective antimicrobial activity against Phophyromonas gingivalis, Staphylococcus aureus and Candida albicans. These findings highlight the potential of Lvloaded CAP-based in-situ implant systems as promising candidates for localized depot delivery systems, particularly after exposure to physiological fluids such as crevicular fluid for the treatment of periodontitis.

A solvent-exchangeable in situ gel (ISG) system was developed for the localized and sustained delivery of salicylic acid (SAL) using a myristic acid (MYR) based lipid matrix. Upon exposure to aqueous environments, the ISG undergoes a sol-to-gel transition, forming a semisolid matrix that enables prolonged drug retention and controlled release. Confocal laser scanning microscopy demonstrated effective permeation, while powder X-ray diffraction confirmed a reduction in crystallinity following gelation, evidenced by broad peaks around 8° 2θ indicative of amorphous or semicrystalline transformation. Molecular dynamics (MD) simulations were employed to investigate the phase behavior, structural organization, and drug release mechanisms of SAL-loaded MYR-based ISGs, particularly in the SN30M25 system. MD simulations (0-200 ns) revealed early stage solvent migration and molecular rearrangement. MYR and N-methyl-2-pyrrolidone (NMP) reached equilibrium rapidly (∼20 ns), while water (WAT) and SAL equilibrated more slowly (30 and 60 ns, respectively), suggesting greater molecular mobility of SAL and WAT. This was supported by diffusion coefficients, where SAL (6.2357 m2/s) and WAT (20.8941 m2/s) exhibited higher values than MYR (3.2271 m2/s) and NMP (1.5345 m2/s). Radius of gyration (Rg) analysis showed more extended conformations for SAL and WAT, whereas MYR and NMP exhibited compact structures, implying stronger molecular aggregation. These findings suggest that SAL disrupts MYR packing, enhances solvent diffusion, and influences the gel matrix behavior. Overall, this study provides molecular-level insights into the structural dynamics of lipid-based ISGs and supports their potential for targeted and sustained drug delivery in oral applications.

Benzydamine hydrochloride (Bz), classified as a nonsteroidal anti-inflammatory drug, has limited its application to topical administration. Bz emerges as a promising candidate for development of solvent removal in-situ forming gel (ISG) in this research aimed at addressing periodontitis treatment. The 40% w/w cellulose acetate butyrate (CAB) was evaluated as an ISG matrix-forming agent, with varying concentrations of Bz to examine the role of drug concentration on ISG’s physicochemical attributes. The drug release kinetics, antimicrobial efficacy, and anti-inflammatory performance of developed ISG were assessed. The formulations, all featuring identical percentages of CAB, exhibited consistent physicochemical characteristics and matrix formation properties triggered by solvent exchange and removal in macroscopic and microscopic examinations. Fluorescence probes tracking with sodium fluorescein and Nile red indicated a delay in solvent movement from CAB matrix formation. X-ray tomographic microscopy and scanning electron microscopy revealed the scaffold CAB-based ISG morphology after Bz release from solvent and drug diffusions. The 3% w/w Bz-loaded CAB-ISG prolonged drug release spanning over 7 days involving the relaxation of the polymeric network and exhibiting non-Fickian diffusion. Numerical simulations indicated that the CAB matrix effectively modulated the Bz release rate. The ISG showcased heightened antimicrobial efficacy against standard microbes and periodontitis pathogen. Additionally, the anti-inflammatory effects were attained by inhibiting protein denaturation in egg albumin and efficiently reducing the expression of IL-1β from LPS-induced human U937 macrophage assay. Consequently, the solvent removal Bz-loaded CAB-ISG stands out as a promising treatment option for periodontitis, offering sustained drug delivery and effective microbial inhibition and especially anti-inflammatory.

This study investigates the incorporation of block natural rubber (NR) as a viscosity-inducing agent in NR oily liquids designed for drug delivery systems. A variety of liquids, encompassing natural oils, synthetic and non-oil liquids, and a eutectic mixture, were incorporated with NR using solvent displacement technique. Successful formulations were achieved for several oily liquids, with viscosity correlating to NR concentration. Particularly, a eutectic mixture of menthol and camphor exhibited optimal viscosity by direct dissolving enabling the development of transdermal ibuprofen delivery and injectable azithromycin for periodontitis treatment. NR prolonged the release of both drugs. The extended-release ibuprofen system holds promise for transdermal applications, while the azithromycin system displayed inhibitory effects against Staphylococcus aureus, Streptococcus mutans, and Porphyromonas gingivalis, suggesting potential for periodontitis treatment. Overall, this investigation advances the development of NR oily liquids as a versatile drug delivery system that can be applied both on the skin and for the local injection into the periodontal pocket, showcasing promise for various therapeutic applications.

Cellulose acetate butyrate is a biodegradable cellulose ester bioplastic produced from plentiful natural plant-based resources. Solvent-exchange-induced in situ gels are particularly promising for periodontitis therapy, as this dosage form allows for the direct delivery of high concentrations of antimicrobial agents to the localized periodontal pocket. This study developed an in situ gel for periodontitis treatment, incorporating a combination of metronidazole and doxycycline hyclate, with cellulose acetate butyrate serving as the matrix-forming agent. Consequently, assessments were conducted on the physicochemical properties, gel formation, drug permeation, drug release, morphological topography, and antimicrobial activities of the formulation. The formulation demonstrated an increased slope characteristic of Newtonian flow at higher bioplastic concentrations. The adequate polymer concentration facilitated swift phase inversion, resulting in robust, solid-like matrices. The mechanical characteristics of the transformed in situ gel typically exhibit an upward trend as the polymer concentration increased. The utilization of sodium fluorescein and Nile red as fluorescent probes effectively tracked the interfacial solvent-aqueous movement during the phase inversion of in situ gels, confirming that the cellulose acetate butyrate matrix delayed the solvent exchange process. The initial burst release of metronidazole and doxycycline hyclate was minimized, achieving a sustained release profile over 7 days in in situ gels containing 25% and 40% cellulose acetate butyrate, primarily governed by a diffusion-controlled release mechanism. Metronidazole showed higher permeation through the porcine buccal membrane, while doxycycline hyclate exhibited greater tissue accumulation, both influenced by polymer concentration. The more highly concentrated polymeric in situ gel formed a uniformly porous structure. Metronidazole and doxycycline hyclate-loaded in situ gels showed synergistic antibacterial effects against S. aureus and P. gingivalis. Over time, the more highly concentrated polymeric in situ gel showed superior retention of antibacterial efficacy due to its denser cellulose acetate butyrate matrix, which modulated drug release and enhanced synergistic effects, making it a promising injectable treatment for periodontitis, particularly against P. gingivalis.