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In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex

Year 2022, Volume: 26 Issue: 4, 873 - 883, 28.06.2025

Heybet Kerem Polat

Abstract

This research aims to increase the solubility of Dexamethasone (Dex) using cyclodextrin and develop a temperature-triggered in situ gelling system for the ocular application. The solubility of Dex was increased with SBE-β-CD. Dex- SBE-β-CD inclusion complex was prepared with kneading and freeze-drying method. Structural characterization was carried out using DSC and FT-IR. When in situ gel formulations were prepared, Pluronic F127 (PF127), a thermosensitive polymer, and Chitosan (CH), a natural, biodegradable, and mucoadhesive hydrophilic polymer, were used together. When the solubility diagrams of the drug-cyclodextrin inclusion complex were examined, it was determined that SBE-β CD showed a linear increase, and AL-type diagram was selected in consequence. The formulations were produced using different amounts of PF127 and a fixed ratio of CH. In situ gels were evaluated for clarity, pH, gelation temperature, and rheological behaviors and selected one formulation. It was established that the formulations were clear, their pH was 6, their gelation temperature decreased with increasing PF127, and was between 22-34 °C. For the selected formulation, 0.1% Dex and Dex/ SBE-β-CD were transferred to in situ gelling systems. As a result of in vitro release studies, it was observed that the release of the Dex/SBE-β-CD inclusion complex containing BRN formulation showed a higher burst effect than the other and was released for 6 hours. The results exhibited that the combination of PF127 and CH has potential as an in situ gelling systems for ocular delivery of Dex and Dex/ SBE-β-CD.

Keywords

Dexamethasone In Situ Gel Ocular Drug Delivery SBE-β- Cyclodextrin Chitosan

References

  • [1]. Nanjawade BK, Manvi F, Manjappa A. RETRACTED: In situ-forming hydrogels for sustained ophthalmic drug delivery. Journal of Controlled Release. 2007; 122: 119-134. [CrossRef]
  • [2]. Srividya B, Cardoza RM, Amin P. Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling system. Journal of controlled release. 2001; 73: 205-211. [CrossRef]
  • [3]. Liu Z, Li J, Nie S, Liu H, Ding P, Pan W. Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin. International journal of pharmaceutics. 2006; 315: 12-17. [CrossRef]
  • [4]. Wei G, Xu H, Ding PT, Zheng JM. Thermosetting gels with modulated gelation temperature for ophthalmic use: the rheological and gamma scintigraphic studies. Journal of Controlled Release. 2002; 83 :65-74. [CrossRef]
  • [5]. Almeida H, Amaral MH, Lobão P, Lobo JMS. In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug discovery today. 2014; 19: 400-412. [CrossRef]
  • [6]. Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharmaceutical research. 2006; 23: 2709-2728. [CrossRef]
  • [7]. Muxika A, Etxabide A, Uranga J, Guerrero P, De La Caba K. Chitosan as a bioactive polymer: Processing, properties and applications. International Journal of Biological Macromolecules. 2017; 105: 1358-1368. [CrossRef]
  • [8]. Lumry WR. A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis. Journal of allergy and clinical immunology. 1999; 104: 150-159. [CrossRef]
  • [9] Beig, A., Agbaria, R., & Dahan, A. Oral delivery of lipophilic drugs: the tradeoff between solubility increase and permeability decrease when using cyclodextrin-based formulations. PLoS One.2013; 8(7), e68237. [CrossRef]
  • [10] Dahan, A., & Hoffman, A. The effect of different lipid based formulations on the oral absorption of lipophilic drugs: the ability of in vitro lipolysis and consecutive ex vivo intestinal permeability data to predict in vivo bioavailability in rats. European journal of pharmaceutics and biopharmaceutics.2007; 67(1), 96-105 . [CrossRef]
  • [11]. Weijtens O, Schoemaker RC, Romijn FP, Cohen AF, Lentjes EG, van Meurs JC. Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate. Ophthalmology. 2002; 109: 1887-1891. [CrossRef]
  • [12]. Aiassa V, Zoppi A, Becerra MC, Albesa I, Longhi MR. Enhanced inhibition of bacterial biofilm formation and reduced leukocyte toxicity by chloramphenicol: β-cyclodextrin: N-acetylcysteine complex. Carbohyd Polym. 2016; 152: 672-678. [CrossRef]
  • [13]. Jithan A, Mohan CK, Vimaladevi M. Development and evaluation of a chloramphenicol hypertonic ophthalmic solution. Indian journal of pharmaceutical sciences. 2008; 70:66. [CrossRef]
  • [14]. Zuorro A, Fidaleo M, Lavecchia R. Solubility Enhancement and Antibacterial Activity of Chloramphenicol Includedin Modified β-Cyclodextrins. Bulletin of the Korean Chemical Society. 2010; 31: 3460-3462. [CrossRef]
  • [15] Gaudana, R., Jwala, J., Boddu, S. H., & Mitra, A. K. (2009). Recent perspectives in ocular drug delivery. Pharmaceutical research, 26(5), 1197-1216. [CrossRef]
  • [16]. Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: basic science and product development. J Pharm Pharmacol. 2010; 62: 1607-1621. [CrossRef]
  • [17] . Rodriguez-Aller M, Guinchard S, Guillarme D, Pupier M, Jeannerat D, Rivara-Minten E, Veuthey JL, Gurny R. New prostaglandin analog formulation for glaucoma treatment containing cyclodextrins for improved stability, solubility and ocular tolerance. Eur J Pharm Biopharm. 2015; 95: 203-214. [CrossRef]
  • [18]. Pramanik A, Sahoo RN, Nanda A, Mohapatra R, Singh R, Mallick S. Ocular permeation and sustained anti-inflammatory activity of dexamethasone from kaolin nanodispersion hydrogel system. Curr Eye Res. 2018; 43: 828-838. [CrossRef]
  • [19]. Roozbahani M, Kharaziha M, Emadi R. pH sensitive dexamethasone encapsulated laponite nanoplatelets: Release mechanism and cytotoxicity. International journal of pharmaceutics. 2017; 518: 312-319. [CrossRef]
  • [20]. Bohorquez M, Koch C, Trygstad T, Pandit N. A study of the temperature-dependent micellization of pluronic F127. Journal of colloid and interface science. 1999; 216: 34-40. [CrossRef]
  • [21]. Okur, N. Ü., Yozgatli, V., & Okur, M. E. In vitro–in vivo evaluation of tetrahydrozoline‐loaded ocular in situ gels on rabbits for allergic conjunctivitis management. Drug Development Research, 2020; 81(6), 716-727. [CrossRef]
  • [22]. Edsman K, Carlfors J, Petersson R. Rheological evaluation of poloxamer as an in situ gel for ophthalmic use. European journal of pharmaceutical sciences. 1998; 6: 105-112. [CrossRef]
  • [23]. Pawar D, Pawar G, Gadhave M, Jadhav S, Gaikwad D. Controlled release in situ forming gatifloxacin HCL hydrogel for ophthalmic drug delivery. Int Res J Pharm. 2012; 3: 86-89.
  • [24]. Aytekin E, Ozturk N, Vural I, Polat HK, Cakmak HB, Calis S, Pehlivan SB. Design of ocular drug delivery platforms and in vitro - in vivo evaluation of riboflavin to the cornea by non-interventional (epi-on) technique for keratoconus treatment. J Control Release. 2020; 324: 238-249. [CrossRef]
  • [25]. Dantas MG, Reis SA, Damasceno CM, et al. Development and evaluation of stability of a gel formulation containing the monoterpene borneol. Sci World J. 2016; 2016) :1 4 [CrossRef]
  • [26] Hiremath, S. S. P., Dasankoppa, F. S., Nadaf, A., Jamakandi, V. G., Mulla, J. S., & Sholapur, H. N. Formulation and evaluation of a novel in situ gum based ophthalmic drug delivery system of linezolid. Scientia Pharmaceutica, 2008;76(3), 515-532. [CrossRef]
  • [27]. Pawar P, Kashyap H, Malhotra S, Sindhu R. Hp--CD-voriconazole in situ gelling system for ocular drug delivery: in vitro, stability, and antifungal activities assessment. BioMed research international. 2013; 2013. [CrossRef]
  • [28]. Srivastava, M., Kohli, K., & Ali, M. Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis. Drug Delivery, 2016; 23(1), 154-166. [CrossRef]
  • [29] Chaudhary, B., & Verma, S. (2014). Preparation and evaluation of novel in situ gels containing acyclovir for the treatment of oral herpes simplex virus infections. The Scientific World Journal, 2014. [CrossRef]
  • [30]. Karatas, Aysegul; BOLUK, Ahsen; HILAL ALGAN, Aslıhan. Poloxamer/Chitosan in situ gelling system for ocular delivery of ofloxacin. Current Drug Therapy, 2014; 9(4): 219-225. [CrossRef]
  • [31]. Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, Porter CJ. Strategies to address low drug solubility in discovery and development. Pharmacol Rev. 2013; 65: 315-499. [CrossRef]
  • [32]. LOFTSSON, Thorsteinn; HREINSDÓTTIR, Dagný; MÁSSON, Már. Evaluation of cyclodextrin solubilization of drugs. International journal of pharmaceutics. 2005; 302(1-2): 18-28 [CrossRef]
  • [33]. Ribeiro A, Figueiras A, Santos D, Veiga F. Preparation and solid-state characterization of inclusion complexes formed between miconazole and methyl-β-cyclodextrin. Aaps Pharmscitech. 2008; 9: 1102-1109. [CrossRef]
  • [34]. Polat HK, Pehlivan SB, Özkul C, Çalamak S, Öztürk N, Aytekin E, Fırat A, Ulubayram K, Kocabeyoğlu S, İrkeç M. Development of besifloxacin HCl loaded nanofibrous ocular inserts for the treatment of bacterial keratitis: In vitro, ex vivo and in vivo evaluation. International journal of pharmaceutics. 2020; 585: 119552. [CrossRef]
  • [35]. El-Kamel A. In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate. International journal of pharmaceutics. 2002; 241: 47-55. [CrossRef]
  • [36]. Gupta H, Jain S, Mathur R, Mishra P, Mishra AK, Velpandian T. Sustained ocular drug delivery from a temperature and pH triggered novel in situ gel system. Drug delivery. 2007; 14: 507-515. [CrossRef]
  • [37]. Karataş A, Sonakin O, KiliÇarslan M, Baykara T. Poly (ε-caprolactone) microparticles containing Levobunolol HCl prepared by a multiple emulsion (W/O/W) solvent evaporation technique: Effects of some formulation parameters on microparticle characteristics. Journal of microencapsulation. 2009; 26: 63-74. [CrossRef]
There are 37 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Delivery Technologies
Journal Section Articles
Authors

Heybet Kerem Polat 0000-0001-5006-3091

Publication Date June 28, 2025
Published in Issue Year 2022 Volume: 26 Issue: 4

Cite

APA Polat, H. K. (2025). In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex. Journal of Research in Pharmacy, 26(4), 873-883.
AMA Polat HK. In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex. J. Res. Pharm. June 2025;26(4):873-883.
Chicago Polat, Heybet Kerem. “In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex”. Journal of Research in Pharmacy 26, no. 4 (June 2025): 873-83.
EndNote Polat HK (June 1, 2025) In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex. Journal of Research in Pharmacy 26 4 873–883.
IEEE H. K. Polat, “In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex”, J. Res. Pharm., vol. 26, no. 4, pp. 873–883, 2025.
ISNAD Polat, Heybet Kerem. “In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex”. Journal of Research in Pharmacy 26/4 (June 2025), 873-883.
JAMA Polat HK. In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex. J. Res. Pharm. 2025;26:873–883.
MLA Polat, Heybet Kerem. “In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex”. Journal of Research in Pharmacy, vol. 26, no. 4, 2025, pp. 873-8.
Vancouver Polat HK. In Situ Gels Triggered by Temperature for Ocular Delivery of Dexamethasone and Dexamethasone/ SBE-β-CD Complex. J. Res. Pharm. 2025;26(4):873-8.