Morphological characteristics of Calendula officinalis L. plant, development and in vitro evaluation of extract loaded topical drug formulation

Öz

Aim: This work aimed to develop microemulsion which can be used as vehicles for the topical application of Calendula officinalis extract. The morphological evaluation and traditional uses of C. officinalis were given in this study.
Methods: The plant specimens of C. officinalis were collected from the botanical garden and deposited in the herbarium. The pseudo-ternary phase diagrams were constructed based on oil and a combination of different surfactant/cosurfactant at different ratios. The selected microemulsions were then characterized for droplet size, polydispersity index, pH, zeta potential and rheology.
Results: Calendula officinalis extract loaded stable microemulsions were successfully formulated based on the selected compositions from the phase diagrams. The developed formulations have shown a globule size of 208.24±2.28, 232.66±4.46 and 254.82±6.84 nm, a polydispersity index of 0.22±0.04, 0.27±0.03, and 0.26±0.03, pH 5.40±0.10, 5.62±0.12, and 5.58±0.08. The formulations appeared transparent and the zeta potential result was neutral. The studied microemulsions showed good stability.
Conclusion: Calendula officinalis extract loaded microemulsion system may be a promising carrier for further development into a topical formulation and clinical trials in the treatment of psoriasis.

Anahtar Kelimeler

• Calendula officinalis
• Topical formulation
• Microemulsion
• Drug delivery system

Calendula officinalis L. bitkisinin morfolojik özellikleri, ekstre içeren topikal ilaç formülasyonu geliştirilmesi ve in vitro değerlendirilmesi

Öz

Amaç: Çalışmamızda Calendula officinalis'in morfolojik değerlendirmesi ve geleneksel kullanımları verilmiştir. Hazırlanan Calendula officinalis ekstresinin topikal uygulabilmesi için taşıyıcı olarak kullanılabilecek mikroemülsiyon geliştirmesi amaçlanmıştır.
Yöntem: Calendula officinalis'in bitki örnekleri botanik bahçesinden toplanmış ve herbaryuma yerleştirilmiştir. Üçgen faz diyagramları, yağ ve farklı oranlarda farklı yüzey aktif madde/yardımcı yüzey aktif maddenin kombinasyonları kullanılarak hazırlanıştır. Seçilen mikroemülsiyonların daha sonra damlacık boyutu, polidispersite indeksi, pH, zeta potansiyeli ve reoloji açısından karakterizasyonları yapılmıştır.
Bulgular: Faz diyagramlarından elde edilen Calendula officinalis ekstresi yüklü kararlı mikroemülsiyonlar başarılı şekilde formüle edilmiştir. Geliştirilen formülasyonlar, 208.24 ± 2.28, 232.66 ± 4.46 ve 254.82 ± 6.84 nm damlacık boyutu, 0.22 ± 0.04, 0.27 ± 0.03 ve 0.26 ± 0.03, pH 5.40 ± 0.10, 5.62 ± 0.12 ve 5.58 ± 0.08 değerinde polidisperslik indeksi göstermiştir. Formülasyonlar şeffaf elde edilmiş ve nötr zeta potansiyel değeri göstermiştir. Mikroemülsiyonların bu çalışmada yüksek kararlılığa sahip oldukları görülmüştür.
Sonuç: Calendula officinalis ekstresi yüklü mikroemülsiyon sistemin, sedef hastalığının klinik araştırmalarında ve topikal tedavisinde kullanılabilmesi için umut vaat edici bir ilaç taşıyıcı olabileceği düşünülmektedir.

Anahtar Kelimeler

• Calendula officinalis
• topikal formülasyon
• mikroemülsiyon
• ilaç taşıyıcı sistem

Kaynakça

1. 1. Peter HD. Flora of Turkey and Aegean Islands. Vol 5. Edinburgh, Edinburgh University Press 1985.
2. 2. Jarić S, et al. Traditional wound-healing plants used in the Balkan region (Southeast Europe). J Ethnopharmacol 2018;211:311-28.
3. 3. Deniz L, Serteser A, Kargıoğlu M. Uşak Üniversitesi ve Yakın çevresindeki bazı bitkilerin mahalli adları ve etnobotanik özellikleri. AKU-FEMÜBİD 2010;10(1):57-72.
4. 4. Uğulu I. Fidelity level and knowledge of medicinal plants used to make therapeutic Turkish baths. Stud Ethno-med 2012;6(1):1-9.
5. 5. Erarslan ZB, Ecevit-Genç G, Kültür Ş. Medicinal plants traditionally used to treat skin diseases in Turkey–eczema, psoriasis, vitiligo. Ankara Ecz Fak Dergisi 2020;44(1):137-66.
6. 6. Greaves MW, Weinstein GD. Treatment of psoriasis. N Engl J Med 1995;332(9):581-89.
7. 7. Naldi L. Epidemiology of psoriasis. Curr Drug Targets Inflamm Allergy 2004;3(2): 121-28.
8. 8. Pandey SS, et al. Cyclosporine laden tailored microemulsion-gel depot for effective treatment of psoriasis: In vitro and in vivo studies. Colloids Surf B Biointerfaces 2020;186:1-8.

9. 9. Ryu KA, et al. Topical delivery of coenzyme q10-loaded microemulsion for skin regeneration. Pharmaceutics 2020;12(4):1-15.
10. 10. Abel EA, et al. Drugs in exacerbation of psoriasis. J Am Acad Dermatol 1986; 15(5):1007–22.
11. 11. Kim GK, James QR. Drug-provoked psoriasis: is it drug induced or drug aggravated?: understanding pathophysiology and clinical relevance. J Clin Aesthet Dermatol 2010; 3(1): 32-38.
12. 12. Rigane G, et al. Investigation into the biological activities and chemical composition of Calendula officinalis L. growing in Tunisia. Int Food Res J 2013; 20(6):3001.
13. 13. Shah RR, et al. Preparation and evaluation of aceclofenac topical microemulsion. Iran J Pharm Res 2010;9(1):5-11.
14. 14. Üstündağ Okur N, Çağlar EŞ, Siafaka PI. Novel ocular drug delivery systems: An update on microemulsions. J Ocul Pharmacol Ther 2020;36(6):342-54.
15. 15. Grampurohit N, Ravikumar P, Mallya R. Microemulsions for topical use–a review. Ind J Pharm Edu Res 2011;45(1):100-07.
16. 16. Das K, Deb S, Karanth T. Phytochemical screening, metallic ion content and from its impact on Anti psoriasis activity of Calendula officinalis and Phlebodium decumanum aqueous leaf extracts in animal experiment model. Galenos 2019;16(3):292-302.
17. 17. Das S, et al. Development of microemulsion based topical ivermectin formulations: Pre-formulation and formulation studies. Colloids Surf. B: Biointerfaces 2020;189:1-8.
18. 18. Öztürk AA, Güven UM. Cefaclor monohydrate loaded microemulsion formulation for topical application: Characterization with new developed UPLC method and stability study. J Pharm Res. 2019;23(3):426-40.
19. 19. Momoh MA, et al. Microemulsion-based approach for oral delivery of insulin: formulation design and characterization. Heliyon 2020;6(3):1-8.
20. 20. Abdulbaqi MR, Rajab NA. Preparation, Characterization and Ex vivo Permeability Study of Transdermal Apixaban O/W Nanoemulsion Based Gel. Iraqi J Pharm Sci 2020;29(2):214-22.
21. 21. Zhang J, Froelich A, Michniak-Kohn B. Topical delivery of meloxicam using liposome and microemulsion formulation approaches. Pharmaceutics 2020;12(3):1-24.
22. 22. Çilek A, Çelebi N, Tirnaksiz F. Lecithin-based microemulsion of a peptide for oral administration: preparation, characterization, and physical stability of the formulation. Drug Deliv 2006;13(1):19-24.
23. 23. Hung WH, et al. Preparation and Evaluation of Azelaic Acid Topical Microemulsion Formulation: In Vitro and In Vivo Study. Pharmaceutics 2021;13(3):1-8.
24. 24. Arora D, Rani A, Sharma AA. Review on phytochemistry and ethnopharmacological aspects of genus Calendula. Pharmacogn Rev 2013;7(14):179-87.
25. 25. Verma PK, et al. Phytochemical ingredients and Pharmacological potential of Calendula officinalis Linn. Int J Pharm Biomed Res 2018;4(2):1-17.
26. 26. Jain A, Pooladanda V, Bulbake U. Liposphere mediated topical delivery of thymoquinone in the treatment of psoriasis. Nanomedicine NBM 2017;13(7):2251-62.
27. 27. Kajbafvala A, Salabat A. Microemulsion and microemulsion gel formulation for transdermal delivery of rutin: Optimization, in-vitro/ex-vivo evaluation and SPF determination. J Dispers Sci Technol 2021;1-16.
28. 28. Çelik A, Türkyılmaz A, Çelebi N. Mikroemülsiyonlar: Genel Özellikleri ve Farmasötik Amaçla Kullanımları. FABAD J Pharm Sci 2002;27:27-41.
29. 29. Banh HL, Cave A. Determination of efficacy and toxicity of diclofenac microemulsion formulation for musculoskeletal pain: an observational study. BMC Res Notes 2020;13(1):1-4.
30. 30. Okur ME, Ayla Ş, Yozgatlı V. Evaluation of burn wound healing activity of novel fusidic acid loaded microemulsion based gel in male Wistar albino rats. Saudi Pharm J 2020;28(3):338-48.
31. 31. Agrawal V, et al. Design and evaluation of microemulsion-based efinaconazole formulations for targeted treatment of onychomycosis through transungual route: Ex vivo and nail clipping studies. Colloids Surf. B: Biointerfaces 2021; 201:1-9.
32. 32. Formariz TP, et al. Doxorubicin biocompatible O/W microemulsion stabilized by mixed surfactant containing soya phosphatidylcholine. Colloids Surf B Biointerfaces 2006;51(1):54-61.