Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel

Heybet Kerem Polat

Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel

Abstract

Corneal neovascularization (CNV) is a serious ocular surface disease that causes the cornea to lose its transparent structure. It is a difficult disease to treat, so different drugs and different carrier systems are tried in the treatment of the disease. One of these methods is the combined application of metformin HCl (MHL) with a fluoroquinolone group antibiotic. The aim of this study is to load MHL with low permeability into a drug delivery system that can prolong the residence time on the ocular surface. In this context, different in situ gel formulations were produced by using poloxamer, a thermosensitive polymer, together with hydroxypropylmethylcellulose, a natural viscosity increaser. In situ gels were evaluated for clarity, pH, gelation temperature, and rheological behaviors and selected two formulation. After loading MHL and moxifloxacin HCl (MOX) into these two formulations, it was determined that they were clear, had a pH of around 7, a gelling temperature of 34-35 °C, and showed pseudoplastic flow. However, drug loading capacities were found to be over 97%.When in vitro release studies were examined, it was determined that both MHL and MOX released for at least six hours. The results showed that the combination of PF127 and HPMC has potential as an in situ gelling systems for ocular delivery of MHL and MOX.

Keywords

References

[1] Roshandel D, Eslani M, Baradaran-Rafii A, Cheung AY, Kurji K, Jabbehdari S, Maiz A, Jalali S, Djalilian AR, Holland EJ. Current and emerging therapies for corneal neovascularization. The ocular surface. 2018; 16:398-414. [CrossRef]
[2] Papathanassiou M, Theodossiadis PG, Liarakos VS, Rouvas A, Giamarellos-Bourboulis EJ, Vergados IA. Inhibition of corneal neovascularization by subconjunctival bevacizumab in an animal model. American journal of ophthalmology. 2008; 145:424-431. e421. [CrossRef]
[3] Oh EJ, Park K, Choi J-S, Joo C-K, Hahn SK. Synthesis, characterization, and preliminary assessment of anti-Flt1 peptide–hyaluronate conjugate for the treatment of corneal neovascularization. Biomaterials. 2009; 30:6026-6034. [CrossRef]
[4] 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]
[5] 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]
[6] 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]
[7] Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharmaceutical research. 2006; 23:2709-2728. [CrossRef]
[8] El-Feky YA, Fares AR, Zayed G, El-Telbany RFA, Ahmed KA, El-Telbany DFA. Repurposing of nifedipine loaded in situ ophthalmic gel as a novel approach for glaucoma treatment. Biomedicine & Pharmacotherapy. 2021; 142:112008. [CrossRef]

[9] Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. Bmj. 2005; 330:1304-1305. [CrossRef]
[10] Tan BK, Adya R, Chen J, Farhatullah S, Heutling D, Mitchell D, Lehnert H, Randeva HS. Metformin decreases angiogenesis via NF-κB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1. Cardiovascular Research. 2009; 83:566-574. [CrossRef]
[11] Joe SG, Yoon YH, Choi JA, Koh J-Y. Anti-angiogenic effect of metformin in mouse oxygen-induced retinopathy is mediated by reducing levels of the vascular endothelial growth factor receptor Flk-1. PloS one. 2015; 10:e0119708. [CrossRef]
[12] Metry M, Shu Y, Abrahamsson B, Cristofoletti R, Dressman JB, Groot D, Parr A, Langguth P, Shah VP, Tajiri T, Mehta MU, Polli JE. Biowaiver monographs for immediate release solid oral dosage forms: metformin hydrochloride. Journal of Pharmaceutical Sciences. 2021; 110:1513-1526. [CrossRef]
[13] Zhu F, Liu D, Wu Q, Zhu Y, Liu Y, Xie X, Li S, Lin H, Chen W. Co-delivery of metformin and levofloxacin hydrochloride using biodegradable thermosensitive hydrogel for the treatment of corneal neovascularization. Drug Delivery. 2019; 26:522-531. [CrossRef]
[14] Kurniawansyah IS, Rusdiana T, Sopyan I, Ramoko H, Wahab HA, Subarnas A. In situ ophthalmic gel forming systems of poloxamer 407 and hydroxypropyl methyl cellulose mixtures for sustained ocular delivery of chloramphenicole: Optimization study by factorial design. Heliyon. 2020; 6:e05365. [CrossRef]
[15] Taymouri S, Tavakoli N, Saeidi A, Akbari V. Thermosensitive hydrogel containing sertaconazole loaded nanostructured lipid carriers for potential treatment of fungal keratitis. Pharmaceutical development and technology. 2019; 24:891-901. [CrossRef]
[16] 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]
[17] Okur NÜ, Yozgatli V, Okur ME. In vitro–in vivo evaluation of tetrahydrozoline‐loaded ocular in situ gels on rabbits for allergic conjunctivitis management. Drug Development Research. 2020; 81:716-727. [CrossRef]
[18] 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]
[19] Polat H, Bozdag S, Özkul C, Calamak S, Ozturk N, Aytekin E, Fırat A, Ulubayram K, Kocabeyoğlu S, Irkec M, Calis S. 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]
[20] Almeida JRGdS, Dantas MGB, Reis SAGB, Damasceno CMD, Rolim LA, Rolim-Neto PJ, Carvalho FO, Quintans-Junior LJ. Development and evaluation of stability of a gel formulation containing the monoterpene borneol. The Scientific World Journal. 2016; 2016. [CrossRef]
[21] Timur SS, Şahin A, Aytekin E, Öztürk N, Polat KH, Tezel N, Gürsoy RN, Çalış S. Design and in vitro evaluation of tenofovir-loaded vaginal gels for the prevention of HIV infections. Pharmaceutical development and technology. 2018; 23:301-310. [CrossRef]
[22] Bansal M, Mittal N, Yadav SK, Khan G, Gupta P, Mishra B, Nath G. Periodontal thermoresponsive, mucoadhesive dual antimicrobial loaded in-situ gel for the treatment of periodontal disease: Preparation, in-vitro characterization and antimicrobial study. Journal of oral biology and craniofacial research. 2018; 8:126-133. [CrossRef]
[23] Kohli K, Srivastava M, Ali M. Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis. Drug Delivery. 2016; 23:154-166. [CrossRef]
[24] Ozturk K. Development and in-vitro characterization of 1-cysteine loaded alginate beads for oral delivery. Journal Of Research In Pharmacy. 2022; 26. [CrossRef]
[25] Ashrafi H, Azadi A. Chitosan-based hydrogel nanoparticle amazing behaviors during transmission electron microscopy. International journal of biological macromolecules. 2016; 84:31-34. [CrossRef]
[26] Adibkia K, Jafari-Aghdam N, Payab S, Barzegar-Jalali M, Parvizpur A, Mohammadi G, Sabzevari A. Methylprednisolone acetate–Eudragit® RS100 electrospuns: Preparation and physicochemical characterization. Artificial cells, nanomedicine, and biotechnology. 2016; 44:497-503. [CrossRef]
[27] Gugleva V, Titeva S, Ermenlieva N, Tsibranska S, Tcholakova S, Rangelov S, Momekova D. Development band evaluation of doxycycline niosomal thermoresponsive in situ gel for ophthalmic delivery. International Journal of Pharmaceutics. 2020; 591:120010. [CrossRef]
[28] 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]
[29] Martínez-Gómez F, Guerrero J, Matsuhiro B, Pavez J. In vitro release of metformin hydrochloride from sodium alginate/polyvinyl alcohol hydrogels. Carbohyd Polym. 2017; 155:182-191. [CrossRef]
[30] Karataş A, Sonakin O, Kilicarslan 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]

Details

Primary Language

English

Subjects

Pharmaceutical Delivery Technologies

Journal Section

Research Article

Authors

Heybet Kerem Polat ^*
0000-0001-5006-3091
Türkiye

Publication Date

June 28, 2025

Submission Date

March 29, 2022

Acceptance Date

June 20, 2022

Published in Issue

Year 2022 Volume: 26 Number: 5

IZ

https://izlik.org/JA83JM55ZB

Cite

RIS / Bibtex

APA

Polat, H. K. (2025). Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel. Journal of Research in Pharmacy, 26(5), 1230-1241. https://izlik.org/JA83JM55ZB

AMA

1.Polat HK. Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel. J. Res. Pharm. 2025;26(5):1230-1241. https://izlik.org/JA83JM55ZB

Chicago

Polat, Heybet Kerem. 2025. “Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel”. Journal of Research in Pharmacy 26 (5): 1230-41. https://izlik.org/JA83JM55ZB.

EndNote

Polat HK (June 1, 2025) Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel. Journal of Research in Pharmacy 26 5 1230–1241.

IEEE

[1]H. K. Polat, “Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel”, J. Res. Pharm., vol. 26, no. 5, pp. 1230–1241, June 2025, [Online]. Available: https://izlik.org/JA83JM55ZB

ISNAD

Polat, Heybet Kerem. “Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel”. Journal of Research in Pharmacy 26/5 (June 1, 2025): 1230-1241. https://izlik.org/JA83JM55ZB.

JAMA

1.Polat HK. Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel. J. Res. Pharm. 2025;26:1230–1241.

MLA

Polat, Heybet Kerem. “Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel”. Journal of Research in Pharmacy, vol. 26, no. 5, June 2025, pp. 1230-41, https://izlik.org/JA83JM55ZB.

Vancouver

1.Heybet Kerem Polat. Design of Metformin HCl and Moxifloxacin HCl Loaded Thermosensitive In Situ Gel. J. Res. Pharm. [Internet]. 2025 Jun. 1;26(5):1230-41. Available from: https://izlik.org/JA83JM55ZB