ROMATİK HASTALIKLARA YÖNELİK OLEUM ROSMARİNİ BAZLI TOPİKAL EMÜLJEL FORMÜLASYONUNUN GELİŞTİRİLMESİ VE İN VİTRO DEĞERLENDİRİLMESİ

Öz

Amaç: Bu çalışmada romatoid artrit tedavisinde kullanılmak üzere Oleum rosmarini içeren y/s tipi emülsiyonlardan topikal bir emüljel formülasyonunun geliştirilmesi ve in vitro karakterizasyonu amaçlanmıştır. Gereç ve Yöntem: In vitro formülasyon çalışmaları ile uygun formülasyonun seçilmesi amacıyla farklı polimer konsantrasyonlarında farklı oranlarda yağ, yüzey aktif madde, kopolimer ve plastizer içeren emülsiyon kombinasyonlarında su fazı olarak Carbopol 996 ve HPMC, yağ fazı olarak Oleum rosmarini kullanılmıştır. Seçilen formülasyonların organoleptik kontrolleri yapılmış ve pH, tekstür profili analizi, reoloji değerlendirmesi ve termodinamik stabilite açısından karakterizasyonları gerçekleştirilmiştir. Sonuç ve Tartışma: Optimize edilen krem formülasyonların pH değeri 5.5-6.5 aralığında olup, formülasyonlar homojen bir şekilde elde edilmiş ve herhangi bir faz ayrımı gözlenmemiştir. Emüljellerin topikal uygulama için uygun viskozite, akış özellikleri, mekanik özellikler gösterdiği ve yüksek termodinamik stabiliteye sahip olduğu belirlenmiştir.

Anahtar Kelimeler

• Esansiyel yağ
• romatoid artrit
• Rosmarinus officinalis
• topikal emüljel

DEVELOPMENT AND IN VITRO EVALUATION OF OLEUM ROSMARINI BASED TOPICAL EMULGEL FORMULATION FOR RHEUMATIC DISEASE

Öz

Objective: In this study, it was aimed to develop a topical emulgel formulation from o/w type emulsions containing Oleum rosmarini, to be used in the treatment of rheumatoid arthritis. Material and Method: Carbopol 996 and HPMC were used as the water phase and Oleum rosmarini was used as oil phase in the emulsion combinations containing oil, surfactant, copolymer and plasticizer at different rates over different polymer concentrations, to select the appropriate formulation with in vitro formulation studies. Organoleptic controls of the selected formulations were made and characterizations were made in terms of pH, texture profile analysis, rheology evaluation and thermodynamic stability. Result and Discussion: The pH value of the optimized formulations was in the range of 5.5-6.5. The formulations were obtained homogeneously, and no phase separation was observed. It has been observed that the emulgels provide suitable viscosity, flow properties, mechanical properties and have high stability for topical application.

Anahtar Kelimeler

• Essential oil
• rheumatoid arthritis
• Rosmarinus officinalis
• topical emulgel

Kaynakça

1. 1. Adami, G., Fassio, A., Rossini, M., Caimmi, C., Giollo, A., Orsolini, G., Viapiana, O., Gatti, D. (2019). Osteoporosis in rheumatic diseases. International Journal of Molecular Sciences, 20(23), 5867.
2. 2. Borges, R.S., Ortiz, B.L.S., Pereira, A.C.M., Keita, H., Carvalho, J.C.T. (2019). Rosmarinus officinalis essential oil: A review of its phytochemistry, anti-inflammatory activity, and mechanisms of action involved. Journal of Ethnopharmacology, 229, 29-45. [CrossRef]
3. 3. Talat, M., Zaman, M., Khan, R., Jamshaid, M., Akhtar, M., Mirza, A.Z. (2021). Emulgel: An effective drug delivery system. Drug Development and Industrial Pharmacy, 47(8), 1193-1199. [CrossRef]
4. 4. Malavi, S., Kumbhar, P., Manjappa, A., Chopade, S., Patil, O., Kataria, U., Dwivedi, J., Disouza, J. (2022). Topical emulgel: Basic considerations in development and advanced research. Indian Journal of Pharmaceutical Sciences, 84(5). [CrossRef]
5. 5. Santos, J., Jimenez, M., Calero, N., Alfaro, M.C., Muñoz, J. (2019). Influence of a shear post-treatment on rheological properties, microstructure and physical stability of emulgels formed by rosemary essential oil and a fumed silica. Journal of Food Engineering, 241, 136-148. [CrossRef]
6. 6. Mohammadifar, M., Aarabi, M.H., Aghighi, F., Kazemi, M., Vakili, Z., Memarzadeh, M.R., Talaei, S.A. (2021). Anti-osteoarthritis potential of peppermint and rosemary essential oils in a nanoemulsion form: behavioral, biochemical, and histopathological evidence. BMC Complementary Medicine and Therapies, 21, 1-12. [CrossRef]
7. 7. Bogdan, C., Moldovan, M.L., Man, I.M., Crișan, M. (2016). Preliminary study on the development of an antistretch marks water-in-oil emulgel: Ultrasound assessment, texture analysis, and sensory analysis. Clinical, Cosmetic and Investigational Dermatology, 249-255. [CrossRef]
8. 8. Jhawat, V., Gupta, S., Saini, V. (2016). Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid. Drug Delivery, 23(9), 3573-3581. [CrossRef]

9. 9. Güven, U.M., Çevikelli, T., Songüloğlu, S., Kayıran, S.D. (2023). Preparation and in vitro characterization of lidocaine loaded aloe vera gel formulation for the treatment of burn wounds. Journal of Faculty of Pharmacy of Ankara University, 47(3), 1041-1052. [CrossRef]
10. 10. Cevher, E., Taha, M.A.M., Orlu, M., Araman, A. (2008). Evaluation of mechanical and mucoadhesive properties of clomiphene citrate gel formulations containing carbomers and their thiolated derivatives. Drug Delivery, 15(1), 57-67. [CrossRef]
11. 11. Yayé, H.S., Faucheron, A., Dupont, L., El Kouari, F., Fekkar, A., Bellanger, A., Tilleul, P. (2020). Management of diabetic foot ulcers: A 25% lidocaine topical emulgel formulation design, physicochemical and microbiological assessments. European Journal of Hospital Pharmacy, 27(3), 162-167. [CrossRef]
12. 12. Labib, R.M., Ayoub, I.M., Michel, H.E., Mehanny, M., Kamil, V., Hany, M., Magdy, M., Moataz, A., Maged, B., Mohamed, A. (2019). Appraisal on the wound healing potential of Melaleuca alternifolia and Rosmarinus officinalis L. essential oil-loaded chitosan topical preparations. PLoS One, 14(9). [CrossRef]
13. 13. Takaki, I., Bersani-Amado, L.E., Vendruscolo, A., Sartoretto, S.M., Diniz, S.P., Bersani-Amado, C. A., Cuman, R.K.N. (2008). Anti-inflammatory and antinociceptive effects of Rosmarinus officinalis L. essential oil in experimental animal models. Journal of Medicinal Food, 11(4), 741-746. [CrossRef]
14. 14. Andrade, J.M., Faustino, C., Garcia, C., Ladeiras, D., Reis, C.P., Rijo, P. (2018). Rosmarinus officinalis L.: An update review of its phytochemistry and biological activity. Future Science OA, 4(4). [CrossRef]
15. 15. Wei, T., Liu, Y., Li, M. (2021). Anti-inflammatory and anti-arthritic activity of rosmarinic acid isolated from rosmarinus officinalis in an experimental model of arthritis. Indian Journal of Pharmaceutical Education and Research, 55, 507-516. [CrossRef]
16. 16. Gilbert, L., Picard, C., Savary, G., Grisel, M. (2013). Rheological and textural characterization of cosmetic emulsions containing natural and synthetic polymers: relationships between both data. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 421, 150-163. [CrossRef]
17. 17. Jorge, L.L., Feres, C.C., Teles, V.E. (2010). Topical preparations for pain relief: Efficacy and patient adherence. Journal of Pain Research, 4, 11-24. [CrossRef]
18. 18. Gwarzo, I.D., Mohd Bohari, S.P., Abdul Wahab, R., Zia, A. (2022). Recent advances and future prospects in topical emulgels from medicinal plants to expedite wound healing: A review. Biotechnology & Biotechnological Equipment, 36(1), 82-94. [CrossRef]
19. 19. Chauhan, L., Gupta, S. (2020). Creams: A review on classification, preparation methods, evaluation and its applications. Journal of Drug Delivery and Therapeutics, 10(5-s), 281-289. [CrossRef]
20. 20. Bhowmik, D., Gopinath, H., Kumar, B.P., Duraivel, S., Kumar, K.P.S. (2012). Recent advances in novel topical drug delivery system. The Pharma Innovation, 1(9), 12-31.
21. 21. Ionova, Y., Wilson, L. (2020). Biologic excipients: Importance of clinical awareness of inactive ingredients. PLoS One, 15(6). [CrossRef]
22. 22. Safitri, F.I., Nawangsari, D., Febrina, D. (2021, January). Overview: Application of carbopol 940 in gel. In International Conference on Health and Medical Sciences (AHMS 2020), 34, 80-84. [CrossRef]
23. 23. Hamdi, N.A.M., Azmi, N.A., Sabari, N.H.M., Harun, A.F., Haris, M.S. (2023). An insight into the use and advantages of Carbopol in topical mucoadhesive drug delivery system: A systematic review. Journal of Pharmacy, 3(1), 53-65.
24. 24. Guarve, K., Kriplani, P. (2021). HPMC-a marvel polymer for pharmaceutical industry-patent review. Recent advances in drug delivery and formulation: Formerly Recent Patents on Drug Delivery & Formulation, 15(1), 46-58. [CrossRef]
25. 25. Pan, P., Svirskis, D., Waterhouse, G.I., Wu, Z. (2023). Hydroxypropyl methylcellulose bioadhesive hydrogels for topical application and sustained drug release: The effect of polyvinylpyrrolidone on the physicomechanical properties of hydrogel. Pharmaceutics, 15(9), 2360. [CrossRef]
26. 26. Kothekar, S.C., Ware, A.M., Waghmare, J.T., Momin, S.A. (2007). Comparative analysis of the properties of Tween‐20, Tween‐60, Tween‐80, Arlacel‐60, and Arlacel‐80. Journal of Dispersion Science and Technology, 28(3), 477-484. [CrossRef]
27. 27. Çevikelli, T., Güven, U.M., Öztürk, A.A. (2024). Metronidazole loaded novel microemulsion formulation for topical delivery and characterization with validated new UPLC method. Fabad Journal of Pharmaceutical Sciences, 49(1), 111-128. [CrossRef]
28. 28. Çevikelli, T., Onan, D., Güven, U.M., Demirtürk, E. (2020). Preparation, characterization and in-vitro evaluation of theophylline loaded microemulsion formulations. Journal of Pharmaceutical Technology, 1(1), 7-12. [CrossRef]
29. 29. Jacob, S.E., Scheman, A., McGowan, M.A. (2018). Propylene glycol. Dermatitis, 29(1), 3-5. [CrossRef]
30. 30. Fiume, M.M., Bergfeld, W.F., Belsito, D.V., Hill, R.A., Klaassen, C.D., Liebler, D., Marks, J.G., Shank, R.C., Slaga, T.J., Snyder, P.W., Andersen, F.A. (2012). Safety assessment of propylene glycol, tripropylene glycol, and PPGs as used in cosmetics. International Journal of Toxicology, 31(5), 245S-260S. [CrossRef]
31. 31. Foo, K.S., Bavoh, C.B., Lal, B., Mohd Shariff, A. (2020). Rheology impact of various hydrophilic-hydrophobic balance (HLB) index non-ionic surfactants on cyclopentane hydrates. Molecules, 25(16), 3725. [CrossRef]
32. 32. Lohani, A., Verma, A., Hema, G., Pathak, K. (2021). Topical delivery of geranium/calendula essential oil‐entrapped ethanolic lipid vesicular emulgel to combat skin aging. BioMed Research International, 2021(1), 4593759. [CrossRef]
33. 33. Simões, A., Miranda, M., Cardoso, C., Veiga, F., Vitorino, C. (2020). Rheology by design: A regulatory tutorial for analytical method validation. Pharmaceutics, 12(9), 820. [CrossRef]
34. 34. Derwin, R., Patton, D., Avsar, P., Strapp, H., Moore, Z. (2022). The impact of topical agents and dressing on pH and temperature on wound healing: A systematic, narrative review. International Wound Journal, 19(6), 1397-1408. [CrossRef]
35. 35. Mancini, G., Gonçalves, L.M., Marto, J., Carvalho, F.A., Simões, S., Ribeiro, H.M., Almeida, A.J. (2021). Increased therapeutic efficacy of SLN containing etofenamate and ibuprofen in topical treatment of inflammation. Pharmaceutics, 13(3), 328. [CrossRef]
36. 36. Çağlar, E.Ş., Güven, G.K., Okur, N.Ü. (2023). Preparation and characterization of carbopol based hydrogels containing dexpanthenol. Journal of Faculty of Pharmacy of Ankara University, 47(3), 770-783. [CrossRef]
37. 37. Namjoshi, S., Dabbaghi M., Roberts, M.S., Grice, J.E., Mohammed, Y. (2020). Quality by design: Development of the quality target product profile (QTPP) for semisolid topical products. Pharmaceutics, 12(3), 287. [CrossRef]
38. 38. Calixto, L.S., Infante, V.H.P., Maia Campos, P.M. (2018). Design and characterization of topical formulations: correlations between instrumental and sensorial measurements. AAPS PharmSciTech, 19, 1512-1519. [CrossRef]
39. 39. Mehta, S., Kaur G., Bhasin, K. (2010). Tween-embedded microemulsions-physicochemical and spectroscopic analysis for antitubercular drugs. AAPS PharmSciTech, 11, 143-153. [CrossRef]
40. 40. Yılmaz Usta, D., Teksin, Z.S., Tugcu Demiroz, F. (2024). Evaluation of emulgel and nanostructured lipid carrier-based gel formulations for transdermal administration of ibuprofen: Characterization, mechanical properties, and ex-vivo skin permeation. AAPS PharmSciTech, 25(5), 124. [CrossRef]
41. 41. Trinh, K.T., Glasgow, S. (2012). On the texture profile analysis test. in Proceedings of the Chemeca. Chemeca Wellington, New Zealand.
42. 42. Owczarz, P., Rył, A., Wichłacz, Ż. (2019). Application of texture profile analysis to investigate the mechanical properties of thermosensitive injectable chitosan hydrogels. Progress on Chemistry and Application of Chitin and its Derivatives, (24), 151-163. [CrossRef]
43. 43. Okur, N.Ü., Yozgatlı V., Şenyiğit Z. (2020). Formulation and detailed characterization of voriconazole loaded in situ gels for ocular application. Journal of Faculty of Pharmacy of Ankara University, 44(1), 33-49. [CrossRef]
44. 44. Bu, Y., Pandit, A. (2022). Cohesion mechanisms for bioadhesives. Bioactive Materials, 13, 105-118. [CrossRef]