A Novel Liposomal Serum Development Containing Clindamycin and Hydrocortisone Via Quality By Design (Qbd) Approach

Year 2026, Volume: 46 Issue: 1, 12 - 26, 01.03.2026

Arkan Yashar Barbar , Mehmet Kalayı , Buket Aksu

https://doi.org/10.52794/hujpharm.1696668

https://izlik.org/JA48RM54AX

Abstract

This research used Quality by Design (QbD) to formulate and optimize a liposomal preparation containing clindamycin (CLN) and hydrocortisone (HCN) to improve acne topical treatment by maximizing stability, drug delivery, and therapeutic efficacy while minimizing systemic side effects. Thin-film hydration was used to manufacture liposomes with different lecithin-cholesterol ratios, CLN, and HCN. Pre-formulation solubility and FTIR compatibility tests were done. A factorial design modified CQAs such vesicle size, PDI, and zeta potential. Particle size, drug entrapment efficiency, drug release, spreadability, pH, viscosity, and stability under various storage conditions were assessed for the improved formulation. The enhanced liposomal formulation showed greater colloidal stability with a mean particle size of 401.5 ± 23.6 nm, a PDI of 0.33 ± 0.21, and a zeta potential of-54.3 ± 1.3 mV. CLN and HCN had sustained drug release and high entrapment efficiency (91.1% and 87.3%). The formulation had a skin-compatible pH (6.4 ± 0.1) and an acceptable spreadability (141.11 ± 0.49 g·sec). After three months in various storage conditions, stability testing showed negligible pH and viscosity fluctuation. The QbD-optimized liposomal formulation of CLN and HCN is a stable, effective, and patient-friendly acne topical therapy with anti-inflammatory and antibacterial activities, improved skin penetration, and reduced side effects.

Keywords

Liposome , Clindamycin , Hydrocortisone , Acne Vulgaris , Quality by Design (QbD).

References

• 1. Vasam M, Korutla S, Bohara RA. Acne vulgaris: A review of the pathophysiology, treatment, and recent nanotechnology based advances. Biochem. Biophys. Rep. 2023;36:101578. doi:10.1016/j.bbrep.2023.101578
• 2. Tan AU, Schlosser BJ, Paller AS. A review of diagnosis and treatment of acne in adult female patients. Int. J. Women’s Dermatol. 2018;4(2):56–71. doi:10.1016/j.ijwd.2017.10.006
• 3. Conforti C, Giuffrida R, Fadda S, Fai A, Romita P, Zalaudek I, et al. Topical dermocosmetics and acne vulgaris. Dermatol. Ther. 2020;34(1). doi:10.1111/dth.14436
• 4. Fallah H, Rademaker M. Isotretinoin in the management of acne vulgaris: Practical prescribing. Int. J. Dermatol. 2020;60(4):451–60. doi:10.1111/ijd.15089
• 5. Vasam M, Korutla S, Bohara RA. Acne vulgaris: A review of the pathophysiology, treatment, and recent nanotechnology based advances. Biochem. Biophys. Rep. 2023;36:101578. doi:10.1016/j.bbrep.2023.101578
• 6. Fox L, Csongradi C, Aucamp M, Du Plessis J, Gerber M. Treatment modalities for acne. Molecules. 2016;21(8):1063. doi:10.3390/molecules21081063
• 7. Mohammed MG, Adınarayana SA. Formulation design of hydrocortisone films for the treatment of aphthous ulcers. Turk. J. Pharm. Sci. 2019;16(3):348–55. doi:10.4274/tjps.galenos.2018.75046
• 8. Professor. Steroid therapy – current indications in practice : Indian J. Anaesth. [Internet]. [cited 2025 May 6]. Available rom: https://journals.lww.com/ijaweb/fulltext/2007/51050/steroid_therapy___current_indications_in_practice.4.aspx
• 9. Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, et al. Understanding pharmaceutical quality by design. AAPS J. 2014;16(4):771–83. doi:10.1208/s12248-014-9598-3
• 10. Waghule T, Dabholkar N, Gorantla S, Rapalli VK, Saha RN, Singhvi G. Quality by design (QBD) in the formulation and optimization of liquid crystalline nanoparticles (lcnps): A risk based industrial approach. Biomed. Pharmacother. 2021;141:111940. doi:10.1016/j.biopha.2021.111940
• 11. Agrawal SS, Baliga V, Londhe VY. Liposomal formulations: A recent update. Pharmaceutics. 2024;17(1):36. doi:10.3390/pharmaceutics17010036
• 12. Jaafari MR, Hatamipour M, Alavizadeh SH, Abbasi A, Saberi Z, Rafati S, et al. Development of a topical liposomal formulation of amphotericin B for the treatment of cutaneous leishmaniasis. Int. J. Parasitol. Drugs Drug Resist. 2019;11:156–65. doi:10.1016/j.ijpddr.2019.09.004
• 13. Kumar, L., Suhas, B. S., Pai, G. K., & Verma, R. (2015). Determination of saturated solubility of naproxen using UV visible spectrophotometer. Research Journal of Pharmacy and Technology, 8(7), 825-828.
• 14. Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, et al. Understanding pharmaceutical quality by design. AAPS J. 2014;16(4):771–83. doi:10.1208/s12248-014-9598-3
• 15. Bhattacharjee A, Das PJ, Dey S, Nayak AK, Roy PKr, Chakrabarti S, et al. Development and optimization of besifloxacin hydrochloride loaded liposomal gel prepared by thin film hydration method using 32 full factorial design. Colloids Surf. A Physicochem. Eng. Asp. 2020;585:124071. doi:10.1016/j.colsurfa.2019.124071
• 16. Szymańska I, Żbikowska A, Kowalska M. Physical stability of model emulsions based on ethyl cellulose oleogels. Int. Agrophys. 2020;34(3):289–300. doi:10.31545/intagr/122333
• 17. Mohammed AR, Weston N, Coombes AGA, Fitzgerald M, Perrie Y. Liposome formulation of poorly water soluble drugs: Optimisation of drug loading and ESEM analysis of stability. Int. J. Pharm. 2004;285(1–2):23–34. doi:10.1016/j.ijpharm.2004.07.010
• 18. Sarada NC, Venugopala G, Lakshmipathy R. Preparation and characterization of Cefditoren pivoxil-loaded liposomes for controlled in vitro and in vivo drug release. Int. J. Nanomed. 2015;149. doi:10.2147/ijn.s79994
• 19. Demirtürk E. In vitro evaluation of emulgel formulation for topical application of diclofenac potassium. Cukurova Med. J. 2024;49(2):371–81. doi:10.17826/cumj.1437623
• 20. Fitria Apriani E, Shiyan S, Hardestyariki D, Starlista V, Febriani M. Factorial design for the optimization of clindamycin HCL-loaded ethosome with various concentrations of phospholipon 90g and ethanol. Res. J. Pharm. Technol. 2023;1561–8. doi:10.52711/0974-360x.2023.00255
• 21. Torkaman M, Zare Kazemabadi F. The use of ethyl cellulose polymer to control drug release of hydrocortisone acetate. Orient. J. Chem. 2017;33(04):1976–84. doi:10.13005/ojc/330444
• 22. Sangnim T, Limmatvapirat S, Nunthanid J, Sriamornsak P, Sittikijyothin W, Wannachaiyasit S, et al. Design and characterization of clindamycin-loaded nanofiber patches composed of polyvinyl alcohol and tamarind seed gum and fabricated by electrohydrodynamic atomization. Asian J. Pharm. Sci. 2018;13(5):450–8. doi:10.1016/j.ajps.2018.01.002
• 23. Altamimi MA, Elzayat EM, Qamar W, Alshehri SM, Sherif AY, Haq N, et al. Evaluation of the bioavailability of hydrocortisone when prepared as solid dispersion. Saudi Pharm. J. 2019;27(5):629–36. doi:10.1016/j.jsps.2019.03.004
• 24. Toma I. Development and characterization of loratadine liposomal gel using QBD approach. Farmacia. 2022 Apr
• 25;70(2):204–13. doi:10.31925/farmacia.2022.2.4 25. Shaker S, Gardouh A, Ghorab M. Factors affecting liposomes particle size prepared by ethanol injection method. Res. Pharm. Sci. 2017;12(5):346. doi:10.4103/1735-5362.213979
• 26. Choi S, Kang B, Yang E, Kim K, Kwak MK, Chang P-S, et al. Precise control of liposome size using characteristic time depends on solvent type and membrane properties. Sci. Rep. 2023;13(1). doi:10.1038/s41598-023-31895-z
• 27. Kan P, Tsao C-W, Wang A-J, Su W-C, Liang H-F. A liposomal formulation able to incorporate a high content of paclitaxel and exert promising anticancer effect. J. Drug Deliv. 2011;2011:1–9. doi:10.1155/2011/629234
• 28. Barbălată CI, Tomuță I, Achim M, Boșca AB, Cherecheș G, Sorițău O, et al. Application of the QBD approach in the development of a liposomal formulation with EGCG. J. Pharm. Innov. 2021;17(3):867–80. doi:10.1007/s12247-021-09541-w
• 29. Ranamalla SR, Porfire A, Licarete E, Tefas L, Parvathaneni RP, Varghese OommenP, et al. A QBD strategy to develop curcumin and Sirna co-loaded lipoplexes to combat osteoarthritis-related inflammation and oxidative stress. bioRxiv. 2024; doi:10.1101/2024.11.25.625050
• 30. Barbalata C-I, Porfire AS, Casian T, Muntean D, Rus I, Tertis M, et al. The use of the QBD approach to optimize the co-loading of simvastatin and doxorubicin in liposomes for a synergistic anticancer effect. Pharmaceuticals. 2022;15(10):1211. doi:10.3390/ph15101211
• 31. Alshaer W, Nsairat H, Lafi Z, Hourani OM, Al-Kadash A, Esawi E, et al. Quality by design approach in liposomal formulations: Robust product development. Molecules. 2022;28(1):10. doi:10.3390/molecules28010010
• 32. Németh Z, Csóka I, Semnani Jazani R, Sipos B, Haspel H, Kozma G, et al. Quality by design-driven zeta potential optimisation study of liposomes with charge imparting membrane additives. Pharmaceutics. 2022;14(9):1798. doi:10.3390/pharmaceutics14091798
• 33. Sankar C, Muthukumar S, Arulkumaran G, Shalini S, Sundaraganapathy R, samuel S joji. Formulation and characterization of liposomes containing clindamycin and green tea for anti acne. Res. J. Pharm. Technol. 2019;12(12):5977. doi:10.5958/0974-360x.2019.01038.2
• 34. Mast M-P, Mesquita L, Gan K, Gelperina S, das Neves J, Wacker MG. Encapsulation and release of hydrocortisone from proliposomes govern vaginal delivery. Drug Deliv. Transl. Res. 2022;13(4):1022–34. doi:10.1007/s13346-022-01263-x
• 35. Savjani KT, Gajjar AK, Savjani JK. Drug solubility: Importance and enhancement techniques. ISRN Pharm.2012 Jul 5;2012:1–10. doi:10.5402/2012/195727
• 36. Lukić M, Pantelić I, Savić SD. Towards optimal ph of the skin and topical formulations: From the current state of the art to tailored products. Cosmetics. 2021;8(3):69. doi:10.3390/cosmetics8030069
• 37. Ran F, Mu K, Liu G, Liu Y, Pang Y, Feng G, et al. Preparation, characterization, and wound healing promotion of hydrogels containing glucosyloxybenzyl 2-isobutylmalates extract from Bletilla striata (thunb.) reichb.f. Int. J. Mol. Sci. 2024;25(19):10563. doi:10.3390/ijms251910563
• 38. Umbarkar, M., Thakare, S., Surushe, T., Giri, A., & Chopade, V. (2021). Formulation and evaluation of liposome by thin film hydration method. J Drug Deliv Ther, 11(1), 72-76.