Optimization and Stability Assessment of Clindamycin HCl Transethosome: Exploring the Effects of Ethanol and Tween 80 Concentrations
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Background: Clindamycin HCl is drug commonly used as an anti-acne in conventional topical formulations. However, effectiveness of clindamycin HCl in conventional topical formulations is limited due to poor skin penetration, whereas Propionibacterium acnes colonies in the deeper sebaceous follicle area. To overcome this limitation, transethosome emerged as an innovative drug delivery system capable of enhancing drug permeation through the skin. Objective: This study aimed to optimise clindamycin HCl transethosome formula using a 22-factorial design.Methods: The optimisation was carried out with two factors and two levels, ethanol (20% and 40%) and Tween 80 (15% and 25%), on the responses of particle size, polydispersity index, and entrapment efficiency. Transethosomes were prepared using the thin-layer hydration method. Furthermore, the optimum transethosomes were tested for stability using the ICH Q1A(R2) method. Results: The optimum formula contains 20% ethanol and 15% Tween 80. The optimum transethosome shows a particle size of 240.933 ± 1.488 nm, a polydispersity index (PDI) of 0.177 ± 0.013, and an entrapment efficiency (EE) of 89.401 ± 0.118%. The release model follows zero-order kinetics with an activation energy of 2.978758 cal/mol. The shelf life at 25°C ± 2°C / RH 60% ± 5% is 22.536 days, and at 5°C ± 3°C is 24.572 days. Conclusion: The optimum transethosomal formula of clindamycin HCl exhibited good initial physical characteristics, with particle size below 250 nm, polydispersity index (PDI) of less than 0.3, and high entrapment efficiency (EE). However, the low shelf life indicated a need for further optimisation to achieve long-term stability.
Abdellatif, A. A., & Tawfeek, H. M. (2016). Transfersomal Nanoparticles for Enhanced Transdermal Delivery of Clindamycin. AAPS PharmSciTech; 17; 1067–1074. doi: 10.1208/s12249-015-0441-7.
Abdulbaqi, I. M., Darwis, Y., Khan, N. A., Assi, R. A., & Khan, A. A. (2016). Ethosomal Nanocarriers: The Impact of Constituents and Formulation Techniques on Ethosomal Properties, In Vivo Studies, and Clinical Trials. International Journal of Nanomedicine; 11; 2279–2304. doi: 10.2147/IJN.S105016.
Apriani, E. F., Mardiyanto, M., & Hendrawan, A. (2022). Optimization of Green Synthesis of Silver Nanoparticles from Areca catechu L. Seed Extract with Variations of Silver Nitrate and Extract Concentrations using Simplex Lattice Design Method. Farmacia; 70; 917-924. doi: 10.31925/farmacia.2022.5.18.
Apriani, E. F., Rosana, Y., & Iskandarsyah, I. (2019). Formulation, Characterization, and In Vitro Testing of Azelaic acid Ethosome-Based Cream Against Propionibacterium acnes for the Treatment of Acne. Journal of Advanced Pharmaceutical Technology & Research; 10; 75-80. doi: 10.4103/japtr.JAPTR_289_18.
Apriani, E. F., Shiyan, S., Hardestyariki, D., Starlista, V., & Febriani, M. (2023). Factorial Design for the Optimization of Clindamycin HCl-Loaded Ethosome with Various Concentration of Phospholipon 90G and Ethanol. Research Journal of Pharmacy and Technology, 16(4), 1561-1568. https://doi.org/10.52711/0974-360X.2023.00255
Ascenso, A., Raposo, S., Batista, C., Cardoso, P., Mendes, T., Praça, F. G., Bentley, M. V., & Simões, S. (2015). Development, Characterization, and Skin Delivery Studies of Related Ultradeformable Vesicles: Transfersomes, Ethosomes, and Transethosomes. International Journal of Nanomedicine; 10; 5837–5851. doi: 10.2147/IJN.S86186.
Bendas, E. R., & Tadros, M. I. (2007). Enhanced Transdermal Delivery of Salbutamol Sulfate Via Ethosomes. AAPS PharmSciTech; 8; E107. doi: 10.1208/pt0804107.
Bnyan, R., Khan, I., Ehtezazi, T., Saleem, I., Gordon, S., O'Neill, F., & Roberts, M. (2018). Surfactant Effects on Lipid-Based Vesicle Properties. Journal of Pharmaceutical Sciences; 107; 1237–1246. doi: 10.1016/j.xphs.2018.01.005.
Clancy, D., Hodnett, N., Orr, R., Owen, M., & Peterson, J. (2017). Kinetic Model Development for Accelerated Stability Studies. AAPS PharmSciTech; 18; 1158–1176. doi: 10.1208/s12249-016-0565-4.
Dawson, A. L., & Dellavalle, R. P. (2013). Acne vulgaris. BMJ (Clinical Research Ed.); 346; f2634. doi: 10.1136/bmj.f2634.
Dlamini, N., Mukaya, H. E., Van Zyl, R. L., Chen, C. T., Zeevaart, R. J., & Mbianda, X. Y. (2019). Synthesis, Characterization, Kinetic Drug Release and Anticancer Activity of Bisphosphonates Multi-Walled Carbon Nanotube Conjugates. Materials Science & Engineering C: Materials for Biological Applications; 104; 109967. doi: 10.1016/j.msec.2019.109967.
Dréno, B. (2017). What is New in the Pathophysiology of Acne, an Overview. Journal of the European Academy of Dermatology and Venereology; 31; 8–12. doi: 10.1111/jdv.14374.
Elhalil, A., Tounsadi, H., Elmoubarki, R., Mahjoubi, F. Z., Farnane, M., Sadiq, M., Abdennouri, M., Qourzal, S., & Barka, N. (2016). Factorial Experimental Design for the Optimization of Catalytic Degradation of Malachite Green Dye in Aqueous Solution by Fenton Process. Water Resources and Industry; 15; 41–48. doi: 10.1016/j.wri.2016.07.002.
El-Laithy, H. M., Shoukry, O., & Mahran, L. G. (2011). Novel Sugar Esters Proniosomes for Transdermal Delivery of Vinpocetine: Preclinical and Clinical Studies. European Journal of Pharmaceutics and Biopharmaceutics; 77; 43–55.
Esposito, E., Calderan, L., Galvan, A., Cappellozza, E., Drechsler, M., Mariani, P., Pepe, A., Sguizzato, M., Vigato, E., Dalla Pozza, E., & Malatesta, M. (2022). Ex Vivo Evaluation of Ethosomes and Transethosomes Applied on Human Skin: A Comparative Study. International Journal of Molecular Sciences; 23; 15112. doi: 10.3390/ijms232315112.
Ferrara, F., Benedusi, M., Sguizzato, M., Cortesi, R., Baldisserotto, A., Buzzi, R., Valacchi, G., & Esposito, E. (2022). Ethosomes and Transethosomes as Cutaneous Delivery Systems for Quercetin: A Preliminary Study on Melanoma Cells. Pharmaceutics; 14; 1038. doi: 10.3390/pharmaceutics14051038.
Garg, V., Singh, H., Bhatia, A., Raza, K., Singh, S. K., Singh, B., & Beg, S. (2017). Systematic Development of Transethosomal Gel System of Piroxicam: Formulation Optimization, in Vitro Evaluation, and Ex Vivo Assessment. AAPS PharmSciTech; 18; 58–71. doi: 10.1208/s12249-016-0489-z.
Hong, K., Yao, Q., Golding, J., Pristijono, P., Zhang, X., Hou, X., Yuan, D., Li, Y., Chen, L., Song, K., & Chen, J. (2023). Low Temperature Storage Alleviates Internal Browning of ‘Comte de Paris’ Winter Pineapple Fruit by Reducing Phospholipid Degradation, Phosphatidic Acid Accumulation and Membrane Lipid Peroxidation Processes. Food Chemistry; 404; 134656. doi: 10.1016/j.foodchem.2022.134656.
ICH. (2003). Stability Testing of New Drug Substances and Products. Amsterdam: European Medicines Agency.
Iskandarsyah, I., Masrijal, C. D. P., & Harmita, H. (2020). Effects of Sonication on Size Distribution and Entrapment of Lynestrenol Transferosome. International Journal of Applied Pharmaceutics; 12; 245–247. doi: 10.22159/ijap.2020.v12s1.FF053.
Kamaly, N., Yameen, B., Wu, J., & Farokhzad, O. C. (2016). Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release. Chemical Reviews; 116; 2602–2663. doi: 10.1021/acs.chemrev.5b00346.
Kumar, M. K., Deep, K. C., Verma, S., Kumar, S. A., Kumar, D. D., Kashyap, P., & Prasad, M. S. (2019). Transethosomes and Nanoethosomes: Recent Approach on Transdermal Drug Delivery System. London: IntechOpen.
Li, G., Fan, Y., Fan, C., Li, X., Wang, X., Li, M., & Liu, Y. (2012). Tacrolimus-loaded Ethosomes: Physicochemical Characterization and In Vivo Evaluation. European Journal of Pharmaceutics and Biopharmaceutics; 82; 49–57. doi: 10.1016/j.ejpb.2012.05.011.
Lu, T., & Ten Hagen, T. L. M. (2020). A Novel Kinetic Model to Describe the Ultra-Fast Triggered Release of Thermosensitive Liposomal Drug Delivery Systems. Journal of Controlled Release; 324; 669–678. doi: 10.1016/j.jconrel.2020.05.047.
Mardiyanto, M., Apriani, E. F., & Helyken, F. P. (2023). The Role of Temperature and pH in the Synthesis of Silver Nanoparticles using Areca catechu L. Seed Extract as Bioreductor. Farmacia; 71; 244-253. doi: 10.31925/farmacia.2023.2.3.
Miksusanti, Apriani, E. F., & Bihurini, A. H. B. (2023). Optimization of Tween 80 and PEG-400 concentration in Indonesian Virgin Coconut Oil Nanoemulsion as Antibacterial Against Staphylococcus aureus. Sains Malaysiana; 52; 1259-1272. doi: 10.17576/jsm-2023-5204-17.
Mollerup, S., Friis-Nielsen, J., Vinner, L., Hansen, T. A., Richter, S. R., Fridholm, H., Herrera, J. A., Lund, O., Brunak, S., Izarzugaza, J. M., Mourier, T., Nielsen, L. P., & Hansen, A. J. (2016). Propionibacterium Acnes: Disease-Causing Agent or Common Contaminant? Detection in Diverse Patient Samples by Next-Generation Sequencing. Journal of Clinical Microbiology; 54; 980–987. doi: 10.1128/JCM.02723-15.
Monisha, C., Ganesh, G., Mythili, L., & Radhakrishnan, K. (2019). A Review on Ethosomes for Transdermal Application. Research Journal of Pharmacy and Technology; 12; 3133-3143.
Pathan, I. B., Nandure, H., Syed, S. M., & Bairagi, S. (2016). Transdermal Delivery of Ethosomes as a Novel Vesicular Carrier for Paroxetine Hydrochloride: In Vitro Evaluation and In Vivo Study. Marmara Pharmaceutical Journal; 20; 1–6. doi: 10.12991/mpj.201620113534.
Raj, A., Dua, K., Nair, R. S., Sarath Chandran, C., & Alex, A. T. (2023). Transethosome: An Ultra-Deformable Ethanolic Vesicle for Enhanced Transdermal Drug Delivery. Chemistry and Physics of Lipids; 255; 105315. doi: 10.1016/j.chemphyslip.2023.105315.
Rakesh, R., & Anoop, K. R. (2012). Formulation and Optimization of Nano-Sized Ethosomes for Enhanced Transdermal Delivery of Cromolyn Sodium. Journal of Pharmacy & Bioallied Sciences; 4; 333–340. doi: 10.4103/0975-7406.103274.
Salawu, S. O., & Okoya, S. S. (2023). Temperature Distribution and Thermal Criticality of Kinetics Exothermic Reactant in Concentric Cylinders Subject to Various Boundary Conditions. ChemEngineering; 7; 19. doi: 10.3390/chemengineering7020019.
Somwanshi, S. B. (2019). Development and Evaluation of Novel Ethosomal Vesicular Drug Delivery System of Sesamum indicum L. Seed Extract. Asian Journal of Pharmaceutics (AJP); 12; 1282-S1290. doi: 10.22377/ajp.v12i04.2924.
Varia, U., Joshi, D., Jadeja, M., et al. (2022). Development and Evaluation of Ultradeformable Vesicles Loaded Transdermal Film of Boswellic Acid. Futur Journal of Pharm Sciences; 8; 39. doi: 10.1186/s43094-022-00428-2.
Watkins, E. R., & Newbold, A. (2020). Factorial Designs Help to Understand How Psychological Therapy Works. Frontiers in Psychiatry; 11; 429. doi: 10.3389/fpsyt.2020.00429.
Wu, P. S., Li, Y. S., Kuo, Y. C., Tsai, S. J., & Lin, C. C. (2019). Preparation and Evaluation of Novel Transfersomes Combined with the Natural Antioxidant Resveratrol. Molecules; 24; 600. doi: 10.3390/molecules24030600.
Zeb, A., Qureshi, O. S., Kim, H. S., Cha, J. H., Kim, H. S., & Kim, J. K. (2016). Improved Skin Permeation of Methotrexate Via Nanosized Ultradeformable Liposomes. International Journal of Nanomedicine; 11; 3813–3824. doi: 10.2147/IJN.S109565.
Zhou, Y., Wei, Y. H., Zhang, G. Q., & Wu, X. A. (2010). Synergistic Penetration of Ethosomes and Lipophilic Prodrug on The Transdermal Delivery of Acyclovir. Archives of Pharmacal Research; 33; 567–574. doi: 10.1007/s12272-010-0411-2.
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