Stability evaluation of emulsion-based topical preparations: a valuable potential of dynamic-mechanical thermoanalysis (DMTA) test as a rapid rheological alternative to conventional freeze-thaw test

  • Nebojša Cekić University of Niš – Faculty of Technology in Leskovac; DCP Hemigal, Research and Development Sector
  • Sanela Savić University of Niš – Faculty of Technology in Leskovac; DCP Hemigal, Research and Development Sector
  • Snežana Savić University of Belgrade – Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology
Keywords: topical emulsions, physical stability, accelerated stability test, rheological tests, shelf life

Abstract


The assessment of stability in emulsion-based topical preparations can be approached through real-time monitoring and/or accelerated methods, drawing predictions from pertinent stability-related physicochemical parameters. Ensuring the robustness and durability of topical products during storage, transport, and application necessitates thorough stability testing. However, due to the diversity of emulsion types and their intended use, there is no universal standard test, placing the liability on formulators/manufacturer to tailor appropriate assessments. Notably, topical emulsions, particularly cosmetic variants, often exhibit impressive stability with extended shelf lives. Nonetheless, evaluating their stability and decision-making remain challenging and time-consuming in industrial contexts. This underscores the demand for alternative testing protocols that expedite stability assessments and predict emulsion-based product stability accurately. This article comprehensively surveys literature, enriched with practical insights, exploring core mechanisms behind emulsion stability and prevention of instability. The discussion encompasses diverse approaches to stability assessment, revealing methodologies and parameters under examination during testing. Particular focus is placed on the dynamic-mechanical thermoanalysis (DMTA) method explored as a rapid, rheologically-based alternative to the conventional freeze-thaw test, emphasizing its usefulness for expediting the stability evaluation of emulsion-based topical preparations.

References

Merriam-Webster's Collegiate Dictionary. 11th ed. Springfield, Massachussets: Merriam-Webster Inc.; 2004. 1623 p.

Matthews BR. Regulatory aspects of stability testing in Europe. Drug Dev Ind Pharm. 1999;25(7):831-56.

Cekic ND, Savic SM, Savic SD. Dynamic-mechanical thermoanalysis test: a rapid alternative for accelerated freeze-thaw stability evaluation of W/O emulsions. Drug Dev Ind Pharm. 2019;45(12):1896-906.

International Organisation for Standardisation (ISO). ISO/TR 13097:2013(en) – Guidelines for the characterization of dispersion stability. 2013.

International Organisation for Standardisation (ISO). ISO/TR 18811:2018(en) – Cosmetics — Guidelines on the stability testing of cosmetic products. 2018.

International Federation of Societies of Cosmetic Chemists (IFSCC). The fundamentals of stability testing (IFSCC Monograph No. 2). Weymouth: Micelle Press; 1992.

Badolato GG, Aguilar F, Schuchmann HP, Sobisch T, Lerche D. Evaluation of long term stability of model emulsions by multisample analytical centrifugation. In: Auernhammer GK, Butt HJ, Vollmer D, editors. Surface and interfacial forces – from fundamentals to applications. Progress in Colloid and Polymer Science; vol 134. Berlin, Heidelberg: Springer; 2008.

Lerche D, Sobisch T. Direct and Accelerated Characterization of Formulation Stability. Journal of Dispersion Science and Technology. 2011;32(12):1799-811.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Harmonised Tripartite Guideline Q1A (R2): Stability testing of new drug substances and products. 2003.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Guideline Q1B: Stability testing: Photostability testing of new drug substances and products. 1996.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Guideline Q1C: Stability testing for new dosage forms. 1996.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Guideline Q1D: Bracketing and matrixing designs for stability testing of new drug substances and products. 2002.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Guideline Q1E: Evaluation of stability data. 2003.

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ICH Guideline Q1F: Stability data package for registration applications in climatic zones III and IV. 2006.

Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. 2009 (current consolidated version: 16/08/2023).

Cosmetics Europe. Guidelines on stability testing of cosmetic products. 2004.

Cekic ND, Savic SM, Savic SD. Dynamic-mechanical thermoanalysis test as a high-performance alternative for accelerated freeze-thaw stability testing: a case study of O/W emulsions. Drug Dev Ind Pharm. 2020;46(3):505-20.

Huynh-Ba K. Handbook of stability testing in pharmaceutical development: regulations, methodologies, and best practices. New York: Springer; 2008. 389 p.

Baertschi SW, Alsante KM, Tønnesen HH. A critical assessment of the ICH guideline on photostability testing of new drug substances and products (Q1B): Recommendation for revision. J Pharm Sci. 2010;99(7):2934-40.

Rieger MM. Stability testing of macroemulsions. Cosmetics and toiletries. 1991;106:59-69.

ANVISA National Health Surveillance Agency. ANVISA Cosmetics Products Stability Guide. Quality in Cosmetic Series. 2004.

Mezger T. The Rheology Handbook. Hannover: Vincentz Network; 2020. 528 p.

Lee H, Jin M, Jeon W-J, Kim H, Jung M, Yoo H, et al. Regulatory and safe-use considerations related to stability after opening of nonsterile dosage forms. J Pharm Investig. 2022;52(3):319-29.

Chavda H. In-use stability studies: guidelines and challenges. Drug Dev Ind Pharm. 2021;47(9):1373-91.

European Medicines Agency (EMA). Note for Guidance on in-use stability testing of human medicinal products. 2001.

World Health Organization (WHO). TRS 1010 – Annex 10: WHO guidelines on stability testing of active pharmaceutical ingredients and finished pharmaceutical products. WHO Technical Report Series 1010, 2018.

Particle Sciences – Drug Development Services. Emulsion stability and testing. Technical Brief; vol. 2. 2011.

Tadros TF. Flocculation of emulsions. In: Tadros TF, editor. Emulsions: formulation, stability, industrial applications. Berlin/Boston: Walter de Gruyter GmbH; 2016; p. 113-28.

Tadros TF. Ostwald ripening in emulsions and its prevention. In: Tadros TF, editor. Emulsions: formulation, stability, industrial applications. Berlin/Boston: Walter de Gruyter GmbH; 2016; p. 129-40.

Tadros TF. Phase inversion and its prevention. In: Tadros TF, editor. Emulsions: formulation, stability, industrial applications. Berlin/Boston: Walter de Gruyter GmbH; 2016; p. 161-72.

Aoki T, Decker EA, McClements DJ. Influence of environmental stresses on stability of O/W emulsions containing droplets stabilized by multilayered membranes produced by a layer-by-layer electrostatic deposition technique. Food Hydrocolloids. 2005;19(2):209-20.

Ghosh S, Coupland JN. Factors affecting the freeze–thaw stability of emulsions. Food Hydrocolloids. 2008;22(1):105-11.

Tadros TF. Characterization of emulsions and assessment of their stability. In: Tadros TF, editor. Emulsions: formulation, stability, industrial applications. Berlin/Boston: Walter de Gruyter GmbH; 2016; p. 173-96.

Klang V, Valenta C. Lecithin-based nanoemulsions. J Drug Deliv Sci Technol. 2011;21(1):55-76.

Masmoudi H, Dréau YL, Piccerelle P, Kister J. The evaluation of cosmetic and pharmaceutical emulsions aging process using classical techniques and a new method: FTIR. Int J Pharm. 2005;289(1-2):117-31.

Mcclements DJ. Critical review of techniques and methodologies for characterization of emulsion stability. Crit Rev Food Sci Nutr. 2007;47(7):611-49.

Zografi G. Physical stability assessment of emulsions and related disperse systems: a critical review. J Soc Cosmet Chem. 1982;33:345-58.

Alade OS, Mahmoud M, Al Shehri DA, Sultan AS. Rapid determination of emulsion stability using turbidity measurement incorporating artificial neural network (ann): experimental validation using video/optical microscopy and kinetic modeling. ACS Omega. 2021;6(8):5910-20.

Bernardi DS, Pereira TA, Maciel NR, Bortoloto J, Viera GS, Oliveira GC, et al. Formation and stability of oil-in-water nanoemulsions containing rice bran oil: in vitro and in vivo assessments. J Nanobiotechnology. 2011;9:44.

Đorđević SM, Radulović TS, Cekić ND, Ranđelović DV, Savić MM, Krajišnik DR, et al. Experimental design in formulation of diazepam nanoemulsions: physicochemical and pharmacokinetic performances. J Pharm Sci. 2013;102(11):4159-72.

Mitri K, Shegokar R, Gohla S, Anselmi C, Müller RH. Lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance. Int J Pharm. 2011;414(1-2):267-75.

Isailović T, Ðorđević S, Marković B, Ranđelović D, Cekić N, Lukić M, et al. Biocompatible nanoemulsions for improved aceclofenac skin delivery: formulation approach using combined mixture-process experimental design. J Pharm Sci. 2016;105(1):308-23.

Savic SM, Cekic ND, Savic SR, Ilic TM, Savic SD. 'All-natural' anti-wrinkle emulsion serum with Acmella oleracea extract: A design of experiments (DoE) formulation approach, rheology and in vivo skin performance/efficacy evaluation. Int J Cosmet Sci. 2021;43(5):530-546.

Published
2023/10/27
Section
Review articles