DEKSPANTENOL İÇEREN KARBOPOL ESASLI HİDROJELLERİN HAZIRLANMASI VE KARAKTERİZASYONU

Yıl 2023, , 770 - 783, 20.09.2023

Emre Şefik Çağlar , Gökçe Karaotmarlı Güven , Neslihan Üstündağ Okur

https://doi.org/10.33483/jfpau.1195397

Cited By: 2

Öz

Amaç: Bu çalışmanın amacı, salım modellerini değiştirmek ve piyasa ürününün fizikokimyasal özelliklerini geliştirmek için dekspantenol yüklü hidrojel formülasyonları oluşturmaktır.
Gereç ve Yöntem: Hidrojel formülasyonları yapmak için, %1, %1.5 ve %2 (a/a) konsantrasyonlarında Carbopol Ultrez kullanıldı. Aktif bileşen dekspantenol daha sonra formülasyonlara %5 (a/a) oranında ilave edildi. Formülasyonlar için pH, viskozite, doku profili analizi, yayılabilirlik, biyoadezyon ve in vitro salım özelliklerinin tümü değerlendirildi.
Sonuç ve Tartışma: Formülasyonların cilt uygulaması için uygun olduğu bulundu. TPA analizi, G1 ve G1-DXP'nin formülasyonların düşük sertlik değerinin sırası ile 10.1851.219 ve 30.8541.637 g sahip olduğunu ortaya koydu. Bu formülasyonların biyoadhezyon mukavemeti, önceki formülasyonlardan daha esnek oldukları ve düşük sertlik değerlerine sahip oldukları için arttı. Geliştirilen formülasyonlar ilk üç saatte %50’nin üzerinde DXP salımı gözlenirken piyasa preparatı %10’un üzerine bile çıkamamıştır. İn vitro salım kinetiği çalışmasında tüm formülasyonların Higuchi modeline uyduğu hesaplanmıştır. Sonuç olarak piyasadaki ürünlere göre daha etkin bir ilaç salım sistemi geliştirilmiştir. Halihazırda hazırlanan formülasyonlar, tedavide kullanımları açısından da umut vadeden formülasyonlardır.

Anahtar Kelimeler

Dekspantenol, hidrojel, karakterizasyon, karbopol

PREPARATION AND CHARACTERIZATION OF CARBOPOL BASED HYDROGELS CONTAINING DEXPANTHENOL

Öz

Objective: The purpose of this study is to create dexpanthenol-loaded hydrogel formulations to alter the release patterns and enhance the physicochemical qualities of the market product.
Material and Method: To make hydrogel formulations, Carbopol Ultrez was utilized in concentrations of 1%, 1.5%, and 2% (w/w). The active component dexpanthenol was then added to the formulations at a concentration of 5% (w/w). pH, viscosity, texture profile analysis, spreadability, bioadhesion, and in vitro release characteristics were all assessed for the formulations.
Result and Discussion: The formulations were found to be suitable for cutaneous application. TPA analysis revealed that the G1 and G1-DXP formulations had the hardness value 10.1851.219 and 30.8541.637 g, respectively. That formulations’ bioadhesion strength has grown because they are more flexible than previous formulations while having low hardness values. As such, it has been observed that the formulations release more than 50% of DXP in three hours while the market preparation was not even reach the 10% drug release. In the in vitro release kinetics study, it was calculated that all formulations fit the Higuchi model. As a result, a more effective drug delivery system has been developed compared to the market preparation. The currently prepared formulations are also promising formulations in terms of their use in treatment.

Anahtar Kelimeler

Carbopol, characterization, dexpanthenol, hydrogel

Kaynakça

• 1. Tottoli, E.M., Dorati, R., Genta, I., Chiesa, E., Pisani, S., Conti, B. (2020). Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics, 12(8), 1-30. [CrossRef]
• 2. Jeckson, T.A., Neo, Y.P., Sisinthy, S.P., Gorain, B. (2021). Delivery of therapeutics from layer-by-layer electrospun nanofiber matrix for wound healing: An update. Journal of Pharmaceutical Sciences, 110(2), 635-653. [CrossRef]
• 3. Qu, J., Zhao, X., Liang, Y., Zhang, T., Ma, P.X., Guo, B. (2018). Antibacterial adhesive injectable hydrogels with rapid self-healing, extensibility and compressibility as wound dressing for joints skin wound healing. Biomaterials, 183(July), 185-199. [CrossRef]
• 4. Ayla, S., Okur, M.E., Günal, M.Y., Özdemir, E.M., Çiçek Polat, D., Yoltaş, A., Biçeroğlu, Karahüseyinoğlu, S. (2018). Wound healing effects of methanol extract of Laurocerasus officinalis roem. Biotechnic & Histochemistry, 94(3), 180-188. [CrossRef]
• 5. Moreira, H.R., Marques, A.P. (2022). Vascularization in skin wound healing: Where do we stand and where do we go? Current Opinion in Biotechnology, 73(i), 253-262. [CrossRef]
• 6. Lei, H., Zhao, J., Li, H., Fan, D. (2022). Paramylon hydrogel: A bioactive polysaccharides hydrogel that scavenges ROS and promotes angiogenesis for wound repair. Carbohydrate Polymers, 289, 119467. [CrossRef]
• 7. Su, J., Li, J., Liang, J., Zhang, K., Li, J. (2021). Hydrogel preparation methods and biomaterials for wound dressing. Life, 11(10), 1-22. [CrossRef]
• 8. Opt Veld, R.C., Walboomers, X.F., Jansen, J.A., Wagener, F.A.D.T.G. (2020). Design considerations for hydrogel wound dressings: Strategic and molecular advances. Tissue Engineering-Part B: Reviews, 26(3), 230-248. [CrossRef]
• 9. He, J., Shi, M., Liang, Y., Guo, B. (2020). Conductive adhesive self-healing nanocomposite hydrogel wound dressing for photothermal therapy of infected full-thickness skin wounds. Chemical Engineering Journal, 394, 124888. [CrossRef]
• 10. Hayati, F., Ghamsari, S.M., Dehghan, M.M., Oryan, A. (2018). Effects of carbomer 940 hydrogel on burn wounds: An in vitro and in vivo study. Journal of Dermatological Treatment, 29(6), 593-599. [CrossRef]
• 11. Sorouri, F., Azimzadeh Asiabi, P., Hosseini, P., Ramazani, A., Kiani, S., Akbari, T., Sharifzadeh, M., Shakoori, M., Foroumadi, A., Firoozpour, L., Amin, M., Khoobi, M. (2023). Enrichment of carbopol gel by natural peptide and clay for improving the burn wound repair process. Polymer Bulletin, 80, 5101-5122. [CrossRef]
• 12. Aswathy, S.H., Narendrakumar, U., Manjubala, I. (2020). Commercial hydrogels for biomedical applications. Heliyon, 6(4), E03719. [CrossRef]
• 13. Hurler, J., Engesland, A., Poorahmary Kermany, B., Škalko-Basnet, N. (2012). Improved texture analysis for hydrogel characterization: Gel cohesiveness, adhesiveness, and hardness. Journal of Applied Polymer Science, 125(1), 180-188. [CrossRef]
• 14. Heise, R., Skazik, C., Marquardt, Y., Czaja, K., Sebastian, K., Kurschat, P., Gan, L., Denecke, B., Ekanayake-Bohlig, S., Wilhelm, K.P., Merk, H.F., Baron, J.M. (2012). Dexpanthenol modulates gene expression in skin wound healing in vivo. Skin Pharmacology and Physiology, 25(5), 241-248. [CrossRef]
• 15. Baron, J.M., Glatz, M., Proksch, E. (2020). Optimal support of wound healing: New insights. Dermatology, 236(6), 593-600. [CrossRef]
• 16. Gorski, J., Proksch, E., Baron, J. M., Schmid, D., Zhang, L. (2020). Dexpanthenol in wound healing after medical and cosmetic interventions (postprocedure wound healing). Pharmaceuticals, 13(7), 1-13. [CrossRef]
• 17. Ulger, B.V., Kapan, M., Uslukaya, O., Bozdag, Z., Turkoglu, A., Alabalik, U., Onder, A. (2016). Comparing the effects of nebivolol and dexpanthenol on wound healing: An experimental study. International Wound Journal, 13(3), 367-371. [CrossRef]
• 18. Fonseca, D.F.S., Carvalho, J.P.F., Bastos, V., Oliveira, H., Moreirinha, C., Almeida, A., Silvestre, A.J.D., Vilela, C., Freire, C.S.R. (2020). Antibacterial multi-layered nanocellulose-based patches loaded with dexpanthenol for wound healing applications. Nanomaterials, 10(12), 1-16. [CrossRef]
• 19. Tanrıverdi, S.T., Suat, B., Azizoğlu, E., Köse, F.A., Özer, Ö. (2018). In-vitro evaluation of dexpanthenol-loaded nanofiber mats for wound healing. Tropical Journal of Pharmaceutical Research, 17(3), 387-394. [CrossRef]
• 20. Cevher, E., Sensoy, D., Taha, M.A.M., Araman, A. (2008). Effect of thiolated polymers to textural and mucoadhesive properties of vaginal gel formulations prepared with polycarbophil and chitosan. AAPS PharmSciTech, 9(3), 953-965. [CrossRef]
• 21. Şenyiǧit, Z.A., Karavana, S.Y., Eraç, B., Gürsel, Ö., Limoncu, M.H., Baloǧlu, E. (2014). Evaluation of chitosan based vaginal bioadhesive gel formulations for antifungal drugs. Acta Pharmaceutica, 64(2), 139-156. [CrossRef]
• 22. Karakucuk, A., Tort, S., Han, S., Oktay, A.N., Celebi, N. (2021). Etodolac nanosuspension based gel for enhanced dermal delivery: In vitro and in vivo evaluation. Journal of Microencapsulation, 38(4), 218-232. [CrossRef]
• 23. Tas, Ç., Özkan, Y., Savaser, A., Baykara, T. (2003). In vitro release studies of chlorpheniramine maleate from gels prepared by different cellulose derivatives. Farmaco, 58(8), 605-611. [CrossRef]
• 24. Çulcu, Ö., Tunçel, E., IIbasmis-Tamer, S., Tirnaksiz, F. (2021). Characterization of thermosensitive gels for the sustained delivery of dexketoprofen trometamol for dermal applications. Journal of Gazi University Health Science Institute, 2, 28-44.
• 25. Moore, J.W., Flanner, H.H. (1996). Mathematical comparison of dissolution profiles. In Pharmaceutical Technology, 20(6), 64-74.
• 26. Shah, V.P., Lesko, L.J., Fan, J., Fleischer, N., Handerson, J., Malinowski, H., Makary, M., Ouderkirk, L., Bay, S., Sathe, P., Singh, G.J.P., Iillman, L., Tsong, Y., Williams, R.I. (1997). FDA guidance for industry; dissolution testing of immediate release solid oral dosage forms. Dissolution Technologies, 4(4), 15-22. [CrossRef]
• 27. Suhail, M., Wu, P.C., Minhas, M.U. (2020). Using carbomer-based hydrogels for control the release rate of diclofenac sodium: Preparation and in vitro evaluation. Pharmaceuticals, 13(11), 1-17. [CrossRef]
• 28. Hurler, J., Engesland, A., Poorahmary Kermany, B., Škalko-Basnet, N. (2012). Improved texture analysis for hydrogel characterization: Gel cohesiveness, adhesiveness, and hardness. Journal of Applied Polymer Science, 125(1), 180-188. [CrossRef]
• 29. Kulkarni, V.S., Shaw, C. (2016). Use of polymers and thickeners in semisolid and liquid formulations. In Essential Chemistry for Formulators of Semisolid and Liquid Dosages (pp.43-69). Academic Press. [CrossRef]
• 30. Kulkarni, V.S., Shaw, C. (2016). Preparation and Stability Testing. In Essential Chemistry for Formulators of Semisolid and Liquid Dosages (pp. 99-135). Academic Press. [CrossRef]
• 31. Lukić, M., Pantelić, I., Savić, S.D. (2021). Towards optimal ph of the skin and topical formulations: From the current state of the art to tailored products. Cosmetics, 8(3), 69. [CrossRef]
• 32. Almeida, J.S., Benvegnú, D.M., Boufleur, N., Reckziegel, P., Barcelos, R.C.S., Coradini, K., De Carvalho, L.M., Bürger, M.E., Beck, R.C.R. (2012). Hydrogels containing rutin intended for cutaneous administration: Efficacy in wound healing in rats. Drug Development and Industrial Pharmacy, 38(7), 792-799. [CrossRef]
• 33. Marchiori, M.L., Lubini, G., Dalla Nora, G., Friedrich, R.B., Fontana, M.C., Ourique, A.F., Bastos, M.O., Rigo, L.A., Silva, C.B., Tedesco, S.B., Beck, R.C.R. (2010). Hydrogel containing dexamethasone-loaded nanocapsules for cutaneous administration: Preparation, characterization, and in vitro drug release study. Drug Development and Industrial Pharmacy, 36(8), 962-971. [CrossRef]
• 34. Salah, S., Awad, G.E.A., Makhlouf, A.I.A. (2018). Improved vaginal retention and enhanced antifungal activity of miconazole microsponges gel: Formulation development and in vivo therapeutic efficacy in rats. European Journal of Pharmaceutical Sciences, 114, 255-266. [CrossRef]
• 35. Karakucuk, A., Tort, S., Han, S., Oktay, A.N., Celebi, N. (2021). Etodolac nanosuspension based gel for enhanced dermal delivery: In vitro and in vivo evaluation. 38(4), 218-232. [CrossRef]
• 36. Erel-Akbaba, G., Akbaba, H., Keselik, E., Bahceci, S.A., Senyigit,Z., Temiz, T.K. (2022). Octaarginine functionalized nanoencapsulated system: In vitro and in vivo evaluation of bFGF loaded formulation for wound healing. Journal of Drug Delivery Science and Technology, 71, 103343. [CrossRef]
• 37. Jones, D.S., Woolfson, A.D., Brown, A.F. (1997). Textural analysis and flow rheometry of novel, bioadhesive antimicrobial oral gels. Pharmaceutical Research, 14(4), 450-457. [CrossRef]
• 38. Carvalho, F.C., Calixto, G., Hatakeyama, I.N., Luz, G.M., Gremião, M.P.D., Chorilli, M. (2013). Rheological, mechanical, and bioadhesive behavior of hydrogels to optimize skin delivery systems. Drug Development and Industrial Pharmacy, 39(11), 1750-1757. [CrossRef]
• 39. Özcan, I., Abaci, Ö., Uztan, A.H., Aksu, B., Boyacioǧlu, H., Güneri, T., Özer, Ö. (2009). Enhanced topical delivery of terbinafine hydrochloride with chitosan hydrogels. AAPS PharmSciTech, 10(3), 1024-1031. [CrossRef]
• 40. Tomić, I., Miočić, S., Pepić, I., Šimić, D., Filipović-Grčić, J. (2021). Efficacy and safety of azelaic acid nanocrystal-loaded in situ hydrogel in the treatment of acne vulgaris. Pharmaceutics, 13(4), 567. [CrossRef]
• 41. Siafaka, P.I., Çağlar, E.Ş., Sipahi, H., Charehsaz, M., Aydın, A., Üstündağ Okur, N. (2021). Ocular microemulsion of brinzolamide: Formulation, physicochemical characterization, and in vitro irritation studies based on EpiOcularTM eye irritation assay. Pharmaceutical Development and Technology, 26(7), 765-778. [CrossRef]
• 42. Pukale, S., Pandya, A., Patravale, V. (2021). Synthesis, characterization and topical application of novel bifunctional peptide metallodendrimer. Journal of Drug Delivery Science and Technology, 66, 102925. [CrossRef]
• 43. Daman Huri, M.F., Ng, S.F., Zulfakar, M.H. (2013). Fish oil-based oleogels: Physicochemicals characterisation and in vitro release of betamethasone dipropionate. International Journal of Pharmacy and Pharmaceutical Sciences, 5(3), 458-467.
• 44. Raza, K., Shareef, M.A., Singal, P., Sharma, G., Negi, P., Katare, O.P. (2014). Lipid-based capsaicin-loaded nano-colloidal biocompatible topical carriers with enhanced analgesic potential and decreased dermal irritation. Journal of Liposome Research, 24(4), 290-296. [CrossRef]
• 45. Ameye, D., Mus, D., Foreman, P., Remon, J.P. (2005). Spray-dried Amioca® starch/Carbopol® 974P mixtures as buccal bioadhesive carriers. International Journal of Pharmaceutics, 301(1-2), 170-180. [CrossRef]
• 46. Sipos, E., Szász, N., Vancea, S., Ciurba, A. (2014). Evaluation and selection of gel base for the formulation of dexpanthenol products. Tropical Journal of Pharmaceutical Research, 13(12), 1987-1992. [CrossRef]
• 47. Stozkowska, W. (2002). Effect of vehicles on diclofenac and indomethacin availability. Acta Poloniae Pharmaceutica, 59(4), 253-260.
• 48. Wang, Y.Y., Hong, C.T., Chiu, W.T., Fang, J.Y. (2001). In vitro and in vivo evaluations of topically applied capsaicin and nonivamide from hydrogels. International Journal of Pharmaceutics, 224(1-2), 89-104. [CrossRef]
• 49. Cojocaru, V., Ranetti, A.E., Hinescu, L.G., Ionescu, M., Cosmescu, C., Poștoarcă, A.G., Cinteză, L.O. (2015). Formulation and evaluation of in vitro release kinetics of na3cadtpa decorporation agent embedded in microemulsion-based gel formulation for topical delivery. Farmacia, 63(5), 656-664.
• 50. Gouda, R., Himankar, B., Qing, Z. (2017). Application of mathematical models in drug release kinetics of carbidopa and levodopa ER tablets. Journal of Developing Drugs, 6(2), 1-8. [CrossRef]
• 51. Lee, J., Lee, Y., Kim, J., Yoon, M., Young, W.C. (2005). Formulation of microemulsion systems for transdermal delivery of aceclofenac. Archives of Pharmacal Research, 28(9), 1097-1102. [CrossRef]