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Thermosensitive and mucoadhesive polymer variables affecting development of miconazole nitrate vaginal in situ gelling system

Yıl 2024, Cilt: 28 Sayı: 5, 1472 - 1484, 28.06.2025

Omar Mohammed Alwan Iman Sabah Jafar

Öz

Miconazole nitrate (MNN) is an efficient local antifungal agent with fungistatic and fungicidal activity used for vaginal candidiasis treatment. This study was aimed to formulate and evaluate MNN vaginal in situ thermosensitive mucoadhesive gel to enhance the residence time and potentiate its activity at the infection site. In situ gel formulas of MNN were formulated by employing the cold method using different concentrations of poloxamer P 407 and P188 alone or in combination as thermosensitive polymers and hydroxypropyl methylcellulose K4M (HPMCK4M), HPMCK15M and gellan gum (GG) as mucoadhesive polymers. The developed formulas were evaluated for different in vitro parameters such as gelation time and temperature, clarity, syrangability, pH, content uniformity, viscosity, bioadhesive force, and drug release profile. The results indicated that there is a direct association between the concentrations of poloxamer 188 with gelation temperature while further incorporation of mucoadhesive polymers caused a reduction in gelation temperature. An inverse relationship was observed between polymer molecular weight and concentration with the drug released and a direct relationship with viscosity and mucoadhesive strength. Formula 2 with 18 % P407, 2 % P188 and 0.6% HPMC K4M was selected as the optimal formula with gelation temperature of (34 ±0.033°C), gelation time (4.90 ± 0.012 min), pH value (6.13±0.05), gel spreadability (4.55± 0.02 cm), drug content (99.1 ±0.13 w/v%), mucoadhesion force (0.3136 N) and drug release of (79.5%) over 12 hours. In conclusions and according to obtained results formula 2 could be considered as a doable substitute to ordinary vaginally administered drug delivery systems.

Anahtar Kelimeler

In situ gel mucoadhesion Miconazole Nitrate Poloxamers thermoresponsive

Kaynakça

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Yıl 2024, Cilt: 28 Sayı: 5, 1472 - 1484, 28.06.2025

Omar Mohammed Alwan Iman Sabah Jafar

Öz

Kaynakça

  • [1] Varshosaz J, Tabbakhian M, Salmani Z. Designing of a thermosensitive chitosan/poloxamer in situ gel for ocular delivery of ciprofloxacin. Open Drug Deliv J. 2008; 2: 61-70. http://dx.doi.org/10.2174/1874126600802010061
  • [2] Webber MJ, Tibbitt MW. Dynamic and reconfigurable materials from reversible network interactions. Nat Rev Mater. 2022;7(7):541-556. https://ui.adsabs.harvard.edu/link_gateway/2022NatRM...7..541W/doi:10.1038/s41578-021-00412-x.
  • [3] Chung CK, Fransen MF, van der Maaden K, Campos Y, García-Couce J, Kralisch D, Chan A, Ossendorp F, Cruz LJ. Thermosensitive hydrogels as sustained drug delivery system for CTLA-4 checkpoint blocking antibodies. J Control Release. 2020;323:1-11. https://doi.org/10.1016/j.jconrel.2020.03.050
  • [4] Gelli R, Del Buffa S, Tempesti P, Bonini M, Ridi F, Baglioni P. Multi-scale investigation of gelatin/poly (vinyl alcohol) interactions in water. Colloids Surf A: Physicochem Eng Asp. 2017;532:18-25. http://dx.doi.org/10.1016/j.colsurfa.2017.07.049
  • [5] Patel P, Patel P. Formulation and evaluation of clindamycin HCL in situ gel for vaginal application. Int J Pharm Investig. 2015;5(1):50-56. https://doi.org/10.4103%2F2230-973X.147233
  • [6] Rençber S, Karavana SY, Şenyiğit ZA, Eraç B, Limoncu MH, Baloğlu E. Mucoadhesive in situ gel formulation for vaginal delivery of clotrimazole: formulation, preparation, and in vitro/in vivo evaluation. Pharm Dev Technol. 2017;22(4):551-561. https://doi.org/10.3109/10837450.2016.1163385
  • [7] Hani U, Bhat RS, Shivakumar HG. Formulation design and evaluation of metronidazole microspheres in a bioadhesive gel for local therapy of vaginal candidiasis. Lat Am J Pharm. 2011;30(1):161-167.
  • [8] Cope JE. Mode of action of miconazole on Candida albicans: effect on growth, viability and K+ release. J Gen Microbiol. 1980;119(1):245-251. https://doi.org/10.1099/00221287-119-1-245
  • [9] Xie L, Li Y, Liu Y, Chai Z, Ding Y, Shi L, Wang J. Vaginal Drug Delivery Systems to Control Microbe-Associated Infections. ACS Appl Bio Mater. 2023;6(9):3504-3515. https://doi.org/10.1021/acsabm.3c00097
  • [10] Jøraholmen MW, Basnet P, Tostrup MJ, Moueffaq S, Škalko-Basnet N. Localized therapy of vaginal ınfections and ınflammation: liposomes-ın-hydrogel delivery system for polyphenols. Pharmaceutics. 2019;11(2):53. https://doi.org/10.3390/pharmaceutics11020053
  • [11] Karavana SY, Rençbe S, Şenyiğit ZA, Baloğlu E. A new in-situ gel formulation of itraconazole for vaginal administration. Pharmacol Pharm. 2012;3(04):417-426. http://dx.doi.org/10.4236/pp.2012.34056
  • [12] Kim YT, Shin BK, Garripelli VK, Kim JK, Davaa E, Jo S, Park JS. A thermosensitive vaginal gel formulation with HPgammaCD for the pH-dependent release and solubilization of amphotericin B. Eur J Pharm Sci. 2010;41(2):399-406. https://doi.org/10.1016/j.ejps.2010.07.009
  • [13] Fakhari A, Anand Subramony J. Engineered in-situ depot-forming hydrogels for intratumoral drug delivery. J Control Release. 2015;220(Pt A):465-475. https://doi.org/10.1016/j.jconrel.2015.11.014
  • [14] Ci T, Yuan L, Bao X, Hou Y, Wu H, Sun H, Cao D, Ke X. Development and anti-Candida evaluation of the vaginal delivery system of amphotericin B nanosuspension-loaded thermogel. J Drug Target. 2018;26(9):829-839. https://doi.org/10.1080/1061186x.2018.1434660
  • [15] Permana AD, Utomo E, Pratama MR, Amir MN, Anjani QK, Mardikasari SA, Sumarheni S, Himawan A, Arjuna A, Usmanengsi U, Donnelly RF. Bioadhesive-thermosensitive ın situ vaginal gel of the gel flake-solid dispersion of ıtraconazole for enhanced antifungal activity in the treatment of vaginal candidiasis. ACS Appl Mater Interfaces. 2021;13(15):18128-18141. https://doi.org/10.1021/acsami.1c03422
  • [16] Hani U, Shivakumar H. Development of miconazole nitrate thermosensitive bioadhesive vaginal gel for vaginal candidiasis. Am J Adv Drug Deliv. 2013;1(3):358-368.
  • [17] Hirun N, Kraisit P, Tantishaiyakul V. Thermosensitive polymer blend composed of poloxamer 407, Poloxamer 188 and polycarbophil for the use as mucoadhesive ın situ gel. Polymers (Basel). 2022;14(9):1836. https://doi.org/10.3390/polym14091836.
  • [18] Chen J, Zhou R, Li L, Li B, Zhang X, Su J. Mechanical, rheological and release behaviors of a poloxamer 407/ poloxamer 188/carbopol 940 thermosensitive composite hydrogel. Molecules. 2013;18(10):12415-12425. https://doi.org/10.3390%2Fmolecules181012415
  • [19] 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 Deliv. 2007;14(8):507-515. https://doi.org/10.1080/10717540701606426
  • [20] Gratieri T, Gelfuso GM, Rocha EM, Sarmento VH, de Freitas O, Lopez RF. A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery. Eur J Pharm Biopharm. 2010;75(2):186-193. https://doi.org/10.1016/j.ejpb.2010.02.011
  • [21] Patel AP, Patel JK. Mucoadhesive in-situ gel formulation for vaginal delivery of tenofovir disoproxil fumarate. Indian J Pharm Educ Res. 2020;54:963-970. http://dx.doi.org/10.5530/ijper.54.4.190
  • [22] Bachhav YG, Patravale VB. Microemulsion-based vaginal gel of clotrimazole: formulation, in vitro evaluation, and stability studies. AAPS PharmSciTech. 2009;10(2):476-481. https://doi.org/10.1208/s12249-009-9233-2
  • [23] Sulaiman HT, Jabir SA, Al-Kinani KK. Investigating the effect of different grades and concentrations of ph-sensitive polymer on preparation and characterization of lidocaine hydrochloride as in situ gel buccal spray. Asian J Pharm Clin Res. 2018;11(11):401-407. http://dx.doi.org/10.22159/ajpcr.2018.v11i11.28492
  • [24] Sherafudeen SP, Vasantha PV. Development and evaluation of in situ nasal gel formulations of loratadine. Res Pharm Sci. 2015;10(6):466-476.
  • [25] Lucero H, Vigo J, León H. The influence of antioxidants on the spreadability of α-tocopherol gels. Drug Dev Ind Pharm. 1994;20(14):2315-2322. https://doi.org/10.3109/03639049409050240
  • [26] Alabdly AA, Kassab HJ. Rheological characterization, In vitro release, and Ex vivo permeation of Nefopam Thermosensitive and mucoadhesive intranasal in situ gel. J Pharm Negat Results. 2022;13(3):715-726. https://doi.org/10.47750/pnr.2022.13.03.025
  • [27] Shelke S, Shahi S, Jalalpure S, Dhamecha D, Shengule S. Formulation and evaluation of thermoreversible mucoadhesive in-situ gel for intranasal delivery of naratriptan hydrochloride. J Drug Deliv Sci Technol . 2015;29:238-244. http://dx.doi.org/10.1016/j.jddst.2015.08.003
  • [28] Peleg M. Temperature-viscosity models reassessed. Crit Rev Food Sci Nutr. 2018;58(15):2663-2672. https://doi.org/10.1080/10408398.2017.1325836
  • [29] Shau PA, Dangre PV, Potnis VV. Formulation of thermosensitive in situ otic gel for topical management of otitis media. Indian J Pharm Sci. 2015;77(6):764-770. https://doi.org/10.4103%2F0250-474x.174970
  • [30] Kim J, Chang JY, Kim YY, Kim MJ, Kho HS. Effects of molecular weight of hyaluronic acid on its viscosity and enzymatic activities of lysozyme and peroxidase. Arch Oral Biol. 2018;89:55-64. https://doi.org/10.1016/j.archoralbio.2018.02.007
  • [31] Tuğcu-Demiröz F, Acartürk F, Erdoğan D. Development of long-acting bioadhesive vaginal gels of oxybutynin: formulation, in vitro and in vivo evaluations. Int J Pharm. 2013;457(1):25-39. https://doi.org/10.1016/j.ijpharm.2013.09.003
  • [32] Fakhari A, Corcoran M, Schwarz A. Thermogelling properties of purified poloxamer 407. Heliyon. 2017;3(8):e00390. https://doi.org/10.1016/j.heliyon.2017.e00390
  • [33] Bonacucina G, Cespi M, Misici-Falzi M, Palmieri GF. Rheological, adhesive and release characterisation of semisolid Carbopol/tetraglycol systems. Int J Pharm. 2006;307(2):129-140. https://doi.org/10.1016/j.ijpharm.2005.09.034
  • [34] Majithiya R, Raval A, Umrethia M, Ghosh P, Murthy R. Enhancement of mucoadhesion by blending anionic, cationic and nonionic polymers. Drug Deliv Technol. 2008;8(2):40-45.
  • [35] Rana SJ, Zafar S, Shahzad A, Basit M, Mudassir J, Akhlaq M, Chohan TA, Arshad MS. Preparation of Tamsulosin hydrochloride-loaded mucoadhesive ın situ gelling polymeric formulation for nasal delivery in geriatrics. AAPS PharmSciTech. 2023;24(8):242. https://doi.org/10.1208/s12249-023-02700-x
  • [36] Abdelbary A, Salem HF, Khallaf RA, Ali AM. Mucoadhesive niosomal in situ gel for ocular tissue targeting: In vitro and in vivo evaluation of lomefloxacin hydrochloride. Pharm Dev Technol. 2017;22(3):409-417. https://doi.org/10.1080/10837450.2016.1219916
  • [37] Mohamed M, Jaafar IS, Sabar MH, Jasim MH, Abdulelah FM, Zghair DA. Oily in situ gels as an alternative floating platform for ketoconazole release. Int J Res Pharm Sci. 2020;11(2):2638-2649.
  • [38] Abdeltawab H, Svirskis D, Sharma M. Formulation strategies to modulate drug release from poloxamer based in situ gelling systems. Expert Opin Drug Deliv. 2020;17(4):495-509. https://doi.org/10.1080/17425247.2020.1731469
  • [39] Dholakia M, Thakkar V, Patel N, Gandhi T. Development and characterisation of thermo reversible mucoadhesive moxifloxacin hydrochloride in situ ophthalmic gel. J Pharm Bioallied Sci. 2012;4(Suppl 1):S42-S45. https://doi.org/10.4103%2F0975-7406.94138
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  • [50] Kumar P, Awasthi R, Rai PK, Kumar M, Pramod T. Mucoadhesive in situ gels of local anaesthetic for periodontia. anaesthesia. 2010;2(4): 28-39
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  • [55] Sabar MH, Jaafar IS, Mohamed MBM. In situ gel as platform for ketoconazole slow release dosage form. Int J App Pharm. 2018;10(5):76-80. http://dx.doi.org/10.22159/ijap.2018v10i5.27849
Toplam 55 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İlaç Dağıtım Teknolojileri
Bölüm Articles
Yazarlar

Omar Mohammed Alwan 0009-0000-6392-0670

Iman Sabah Jafar 0000-0003-4517-2327

Yayımlanma Tarihi 28 Haziran 2025
Gönderilme Tarihi 3 Mayıs 2024
Kabul Tarihi 6 Haziran 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 28 Sayı: 5

Kaynak Göster

APA Alwan, O. M., & Jafar, I. S. (2025). Thermosensitive and mucoadhesive polymer variables affecting development of miconazole nitrate vaginal in situ gelling system. Journal of Research in Pharmacy, 28(5), 1472-1484.
AMA Alwan OM, Jafar IS. Thermosensitive and mucoadhesive polymer variables affecting development of miconazole nitrate vaginal in situ gelling system. J. Res. Pharm. Temmuz 2025;28(5):1472-1484.
Chicago Alwan, Omar Mohammed, ve Iman Sabah Jafar. “Thermosensitive and Mucoadhesive Polymer Variables Affecting Development of Miconazole Nitrate Vaginal in Situ Gelling System”. Journal of Research in Pharmacy 28, sy. 5 (Temmuz 2025): 1472-84.
EndNote Alwan OM, Jafar IS (01 Temmuz 2025) Thermosensitive and mucoadhesive polymer variables affecting development of miconazole nitrate vaginal in situ gelling system. Journal of Research in Pharmacy 28 5 1472–1484.
IEEE O. M. Alwan ve I. S. Jafar, “Thermosensitive and mucoadhesive polymer variables affecting development of miconazole nitrate vaginal in situ gelling system”, J. Res. Pharm., c. 28, sy. 5, ss. 1472–1484, 2025.
ISNAD Alwan, Omar Mohammed - Jafar, Iman Sabah. “Thermosensitive and Mucoadhesive Polymer Variables Affecting Development of Miconazole Nitrate Vaginal in Situ Gelling System”. Journal of Research in Pharmacy 28/5 (Temmuz 2025), 1472-1484.
JAMA Alwan OM, Jafar IS. Thermosensitive and mucoadhesive polymer variables affecting development of miconazole nitrate vaginal in situ gelling system. J. Res. Pharm. 2025;28:1472–1484.
MLA Alwan, Omar Mohammed ve Iman Sabah Jafar. “Thermosensitive and Mucoadhesive Polymer Variables Affecting Development of Miconazole Nitrate Vaginal in Situ Gelling System”. Journal of Research in Pharmacy, c. 28, sy. 5, 2025, ss. 1472-84.
Vancouver Alwan OM, Jafar IS. Thermosensitive and mucoadhesive polymer variables affecting development of miconazole nitrate vaginal in situ gelling system. J. Res. Pharm. 2025;28(5):1472-84.