| DOI: 10.29090/psa.2026.03.26.10404 | Pharm Sci Asia 2026; 53(3), 394-408 |
Development of diclofenac and metronidazole thermo-responsive mucoadhesive in situ gel for periodontal drug deliveryYuwakorn Siripithaya 1, Kittiphon Juntaraarpa 2, Jaturaphat Anugul 2, Natthanon Srion 2, Surainee Hayeemasae 3, Seereehan Nuereng 3, Nurasma Dueramae 3, Natthakit Wahab 3, Ekachai Dumkliang 4, Thawatchai Phaechamud 5, Kritamorn Jitrangsri 6,7*
1 The Center for Scientific and Technological Equipment, Walailak University, Nakhon Si Thammarat 80160, Thailand
2 Doctor of Pharmacy Program, School of Pharmacy, Walailak University, Nakhon Si Thammarat 80160, Thailand
3 Bachelor of Chemical Engineering and Pharmaceutical Chemistry Program, School of Engineering and Technology, Walailak University, Nakhon Si Thammarat 80160, Thailand
4 Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90110, Thailand
5 Department of Industrial Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
6 Department of Industrial Pharmacy, School of Pharmacy, Walailak University, Nakhon Si Thammarat 80160, Thailand
7 Biomass and Oil Palm Center of Excellence, Walailak University, Tha Sala, Nakhon Si Thammarat 80160, Thailand
Periodontitis is a chronic inflammatory disease driven by anaerobic bacterial biofilms within periodontal pockets. Conventional oral dosage forms exhibit limitations in pocket retention and sustained drug exposure, necessitating more effective local delivery strategies. This study aimed to develop and optimize a thermo-responsive mucoadhesive in situ gel containing diclofenac (DIC) and metronidazole (MTZ) using a Poloxamer 407/Poloxamer 188 binary system for periodontal drug delivery. A Central Composite Design (CCD) was employed to optimize gelation temperature (Tgel), yielding a significant quadratic model (p < 0.001, R2 = 98.81%). The optimized formulation (P407 16.44% w/w; P188 7.93% w/w) exhibited Tgel = 33.68 ± 0.45 ?C, suitable for syringe-based administration into periodontal pockets followed by in situ solidification at physiological temperature. Drug-loaded formulations demonstrated enhanced mucoadhesive strength compared with the blank gel. The BSA denaturation assay confirmed significant anti-inflammatory activity in DIC-containing formulations, with the dual-drug gel (G-DM) achieving 82.13% inhibition relative to the poloxamer matrix baseline. Antimicrobial testing demonstrated inhibitory activity against Porphyromonas gingivalis, Streptococcus mutans, and MRSA. In vitro drug release showed sustained, diffusion-controlled release of both drugs over 24 hours, markedly superior to the solution control. These findings support the potential of this binary poloxamer-based gel as a dual-action local delivery platform for periodontitis management.
Keyword:
Diclofenac; Metronidazole; Poloxamer; In situ gel; Periodontitis
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