Contents lists available at ScienceDirect Materials Science & Engineering C journal homepage: www.elsevier.com/locate/msec Meloxicam-loaded solvent exchange-induced in situ forming beta- cyclodextrin gel and microparticle for periodontal pocket delivery Sai Myo Thu Rein a,b , Wai Wai Lwin c , Sarun Tuntarawongsa d,e , Thawatchai Phaechamud a,e, ⁎ a Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand b Department of Pharmacognosy, University of Pharmacy, Mandalay, Myanmar c Department of Pharmaceutics, University of Pharmacy, Mandalay, Myanmar d Pharmaceutical Intelligence Unit Prachote Plengwittaya, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand e Natural Bioactive and Material for Health Promotion and Drug Delivery System Group (NBM), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand ARTICLE INFO Keywords: In situ forming gel In situ forming microparticle Periodontal pocket Local delivery Meloxicam Beta-cyclodextrin ABSTRACT The in situ forming system has attracted attention for periodontitis treatment owing to its sustainable drug release localisation at a periodontal pocket. Given its low aqueous solubility, beta-cyclodextrin (β-CD) may serve as a matrix former of solvent exchange-induced in situ forming gel (ISG) and microparticle (ISM). Meloxicam (Mex)-loaded-β-CD ISG and ISM were prepared using β-CD in dimethyl sulphoxide (ISG) as the internal phase and camellia oil comprising 5% glyceryl monostearate as the external phase (ISM). Mex-loaded β-CD systems comprising 40% β-CD were easily injected via a 24-gauge needle. During solvent exchange with phosphate buffer saline (pH 6.8), the highly concentrated β-CD ISG promoted the phase inversion of β-CD aggregates into matrix- like. Upon exposure to aqueous phase, the ISM system comprising 40% β-CD transformed into microparticles and extended the drug release to 7 days with minimised initial burst release following Fickian diffusion. Moreover, the potential degradability was evident from the high weight loss. High maximum deformation force with high viscous character initiated the slow diffusion rate of the solvent from the ISM system. Therefore, 40% β-CD ISM is a potential local Mex-controlled release system of anti-inflammatory drug for periodontitis treatment. 1. Introduction Periodontitis causes chronic inflammation of the gum and tissues surrounding and supporting the teeth [1]. Host immune-inflammatory mediators, such as prostaglandin E2, play important roles in in- flammation and bone resorption of the teeth, which lead to disease progression [2]. Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit these mediators, thereby reducing tissue destruction and bone loss [3,4]. In addition, NSAIDs reduce swelling, acute periodontitis and pain [5]. Thus, NSAIDs have been used as an adjunctive therapy for periodontitis [6]. Meloxicam (Mex), a selective cyclooxygenase-2 inhibitor, is a highly potent NSAID [7]. When administered subcutaneously, Mex can pre- vent alveolar bone loss in experimental periodontitis in rats [8]. Moreover, Mex is a potent inhibitor for acute exudation in periodontal tissues and bone and cartilage destruction [7]. Mex-loaded thermo- sensitive gels can significantly alleviate chronic periodontitis [9]. The plaque index, gingival index and probing depth decrease significantly a month after the treatment with Mex-loaded gels [10]. Solvent exchange-induced in situ forming gel (ISG) contains an aqueous insoluble matrix former that dissolves in organic solvents [11–13]. Phase inversion provokes the transformation from solution into concentrated matrix former phase and solid matrix-like phase after solvent exchange with the aqueous environment. An in situ forming microparticle (ISM) system is an injectable emulsion in which drug- loaded matrix former solution droplets are dispersed in a continuous oil phase containing an emulsion stabiliser [14–16]. Exposure of this emulsion to the aqueous environment after injection hardens the inner polymer droplets, which form microparticles in situ and thereafter prolong drug release [17]. Rungseevijitprapa and Bodmeier [18] pre- pared the internal phase of ISM using poly (D,L-lactide-co-glycolide) and poly (D,L-lactide) dissolved in a biocompatible solvents, such as N-me- thyl-2-pyrrolidone (NMP), 2-pyrrolidone (PYR), dimethyl sulphoxide (DMSO), triacetin or low-molecular-weight polyethylene glycol. Dox- ycycline hyclate-loaded ISM systems were also fabricated using bleached shellac as the polymer of the internal phase and olive oil https://doi.org/10.1016/j.msec.2020.111275 Received 9 March 2020; Received in revised form 9 June 2020; Accepted 5 July 2020 ⁎ Corresponding author at: Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand. E-mail addresses: tuntarawongsa_s@su.ac.th (S. Tuntarawongsa), thawatchaienator@gmail.com, tphaechamud011@yahoo.com (T. Phaechamud). Materials Science & Engineering C 117 (2020) 111275 Available online 08 July 2020 0928-4931/ © 2020 Elsevier B.V. All rights reserved. T