Advertisement

The Role of Excipients in the Microstructure of Topical Semisolid Drug Products

  • Amy Ethier
  • Padam Bansal
  • James Baxter
  • Nigel Langley
  • Norman RichardsonEmail author
  • Amitkumar Mavjibhai Patel
Chapter
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 36)

Abstract

The most common pharmaceutical dosage forms for topical delivery of drugs are creams, ointments, and gels, all of which are semisolid in consistency. Attributes that are critical to the effective performance of pharmaceutical semisolids include viscosity, API status, and bioavailability and shelf-life stability. Recent investigations have demonstrated that these critical attributes are driven by the microscale organization of matter (or microstructure) in the semisolid formulation. The microstructure is, in turn, affected by the selection of excipients, amount of excipients, quality of excipients, as well as the processing methods utilized to manufacture the semisolid product. This chapter explores the role of excipients in the microstructure of creams, ointments, and gels, as well as the impact of microstructure on their critical quality attributes and performance.

Keywords

Excipient Topical Semisolid Microstructure Critical quality attributes 

References

  1. J. Alexander, Colloid Chemistry: An Introduction with Practical Applications (Springer Science + Business Media, New York, 1924), p. 102Google Scholar
  2. T.S. Awad, E.S. Johnson, A. Bureiko, U. Olsson et al. Colloidal structure and physical properties of gel networks containing anionic surfactant and fatty alcohol mixture. J. Disp. Sci. Tech. 32, 807–815 (2011)CrossRefGoogle Scholar
  3. B.W. Barry, Structure and rheology of emulsions stabilized by mixed emulsifiers. Rheol. Acta 10, 96–105 (1971)CrossRefGoogle Scholar
  4. M.D. Barry, R.C. Rowe, The characterization by small-angle X-ray-scattering of a pharmaceutical gel with a lamellar structure. Int. J. Pharm. 53, 139–143 (1989)CrossRefGoogle Scholar
  5. S. Bhide, S. Rangappa, R.M.B. Prado, T. Fatima, S. Kundu, M. Repka, S.N. Murthy, Effect of fatty alcohols on the rheological characteristics of O/W creams, AAPS 2017 Annual Meeting Poster, M8020 (2017a)Google Scholar
  6. S. Bhide, S. Rangappa, T. Fatima, M. Repka, S.N. Murthy, Study of globule size distribution of topical O/W creams containing different fatty alcohols, AAPS Annual Meeting Poster T4106 (2017b)Google Scholar
  7. L. Buhse, R. Kolinski, B. Westenberger, A. Wokovich, J. Spencer, C.W. Chen, S. Turujman, M. Gautam-Basak, G.J. Kang, A. Kibbe, B. Heintzelman, E. Wolfgang, Topical drug classification. Int. J. Pharm. 295, 101–112 (2005)CrossRefGoogle Scholar
  8. G.-S. Chang, J.-S. Koo, K.-W. Song, Wall slip of vaseline in steady shear rheometry. Korea-Aust. Rheol. J. 15, 55–61 (2003)Google Scholar
  9. R.K. Chang, A. Raw, R. Lionberger, L. Yu, Generic development of topical dermatologic products, part II: quality by design for topical semisolid products. AAPS J. 15, 674–683 (2013)CrossRefGoogle Scholar
  10. S. Cimmino, R. Greco, E. Martuscelli, L. Nicolais, C. Silvestre, Blends of poly(ethylene oxide) samples of different molecular wights: Thermal and mechanical properties. Polymer 19, 1079–1082 (1978)CrossRefGoogle Scholar
  11. G.M. Eccleston, The influence of fatty alcohols on the structure and stability of creams prepared with polyethylene glycol-1000 monostearate fatty alcohols. Int. J. Cosm. Sci. 4, 133–142 (1982)CrossRefGoogle Scholar
  12. G.M. Eccleston, Multiple-phase oil-in-water emulsions. J. Soc. Cosm. Chem. 41, 1–22 (1990)Google Scholar
  13. I. Eros, M. Konya, I. Csoka, Study of the structure of coherent emulsions. Int. J. Pharm. 256, 75–84 (2003)CrossRefGoogle Scholar
  14. S. Fu, A. Thacker, D.M. Sperger, R.L. Boni, S. Velankar, E.J. Munson, L.H. Block, Rheological evaluation of inter-grade and inter-batch variability of sodium alginate. AAPS PharmSciTech 11, 1662–1674 (2010)CrossRefGoogle Scholar
  15. German Pharmacopoeia, 8th ed. (Frankfurt am Main Verlag, Stuttgart 1978)Google Scholar
  16. J. J. Hermans (ed.), Flow Properties of Disperse Systems (Interscience Publishers, New York, 1953), pp. 42–46Google Scholar
  17. U. Hoppe, The Lanolin Book (Beiersdorf, Hamburg, 1999)Google Scholar
  18. T. Iwata, Cosmetic Science and Technology: Theoretical Principles and Applications (Elsevier Inc., Amsterdam, 2017)Google Scholar
  19. H.E. Junginger, Colloidal structures of O/W creams. Pharm. Weekbl.Sci. 6, 141–149 (1984)CrossRefGoogle Scholar
  20. H.E. Junginger, Colloidal Drug Delivery Systems (Marcel Dekker Inc., New York, 1994)Google Scholar
  21. R.A. Khalil, A. Zarari, Theoretical estimation of the critical packing parameter of amphiphilic self-assembled aggregates. Appl. Surf. Sci. 318, 85–89 (2014)CrossRefGoogle Scholar
  22. Y.S. Krishnaiah, X. Xu, Z. Rahman, Y. Yang, U. Katragadda, R. Lionberger, J.R. Peters, K. Uhl, M.A. Khan, Development of performance matrix for generic product equivalence of acyclovir topical creams. Int. J. Pharm. 475, 1–13 (2014)CrossRefGoogle Scholar
  23. A.R. Longworth, J.D. French, Quality control of white soft petrolatum. J. Pharm. Pharmacol. 21, 1S–5S (1969)CrossRefGoogle Scholar
  24. Lubrizol, TDS-222: Molecular Weight of Carbopol® and Pemulen™ polymers. (2007), https://www.lubrizol.com/Life-Sciences/Literature/Pharmaceutical-Literature
  25. Lubrizol, Pharmaceutical Bulletin 7: Flow and suspension properties. (2008), https://www.lubrizol.com/Life-Sciences/Literature/Pharmaceutical-Literature
  26. Lubrizol, TDS-237: Neutralizing Carbopol® and Pemulen™ polymers in aqueous and hydroalcoholic systems. (2009), https://www.lubrizol.com/Life-Sciences/Literature/Pharmaceutical-Literature
  27. Lubrizol, Pharmaceutical Bulletin 4: Dispersion techniques. (2011a), https://www.lubrizol.com/Life-Sciences/Literature/Pharmaceutical-Literature
  28. Lubrizol, Pharmaceutical Bulletin 5: Neutralization Procedures. (2011b), https://www.lubrizol.com/Life-Sciences/Literature/Pharmaceutical-Literature
  29. Lubrizol, Pharmaceutical Bulletin 21: Formulating Semisolid Products. (2011c), https://www.lubrizol.com/Life-Sciences/Literature/Pharmaceutical-Literature
  30. Lubrizol, Pharmaceutical Bulletin 30: Lubrizol Pharmaceutical Polymers for controlled release tablets and capsules. (2011d), https://www.lubrizol.com/Life-Sciences/Literature/Pharmaceutical-Literature
  31. Y. Mohammad, S. Namjoshi, K. Telaprolu, N. Jung, H. Benson, M. Windbergs, J. Grice, S. Raney, M. Roberts, The impact of topical semisolid product microstructure and metamorphosis on bioavailability and bioequivalence. AAPS Annual Meeting 2017, Poster T1111 (2017)Google Scholar
  32. K.R. Morris, G.T. Knipp, A.T.M. Serajuddin, Structural properties of polyethylene glycol-Polysorbate 80 mixture, a solid dispersion vehicle. J. Pharm. Sci. 81, 1185–1188 (1992)CrossRefGoogle Scholar
  33. K. Munzel, Versuch einer systematik der salben nach galenischen Gesichtspunkten. Pharma. Acta Helv. 28, 320–333 (1953)Google Scholar
  34. Murthy SN, Characterizing the critical quality attributes and in vitro bioavailability of acyclovir and metronidazole topical products. (2016), https://www.fda.gov/downloads/Drugs/NewsEvents/UCM591897.pdf
  35. Z. Németh et al., Rheological behaviour of a lamellar liquid crystalline surfactant–water system. Colloids Surf. A Physicochem. Eng. Asp. 145, 107–119 (1998)CrossRefGoogle Scholar
  36. O. Robles-Vásquez et al., Rheology of lyotropic liquid crystals of aerosol OT: II. High concentration regime. J. Colloid Interface Sci. 160, 65–71 (1993)CrossRefGoogle Scholar
  37. F. Romanski, A.V. Vladimirova, C. Merritt, N. Richardson, N. Langley, Controlling the physical properties and performance of semi-solid formulations through excipient selection. AAPS Annual Meeting Poster (2015)Google Scholar
  38. S. Savic et al., Topical vehicles based on natural surfactant/fatty alcohols mixed emulsifier: the influence of two polyols on the colloidal structure and in vitro/in vivo skin performance. J. Pharm. Sci. 98, 2073–2090 (2009)CrossRefGoogle Scholar
  39. V.K.E. Schulte, M.A. Kassem, Rheologische Studien an Salbengelen: 6. Mitteilung. Abhangigkeit der rheologischen Eigenschaften eines Polyathyleneglykol-Gels vom Molekulargewicht der Komponenten. Pharm. Acta Helvetiae 39, 383–389 (1964)Google Scholar
  40. United States Pharmacopeia and National Formulary (USP 20-NF15) (United States Pharmacopeial Convention, Rockville, 1979)Google Scholar
  41. United States Pharmacopeia and National Formulary (USP 41-NF 36), General Chapter 1151: Pharmaceutical Dosage Forms (Unites States Pharmacopeial Convention, Rockville, 2018)Google Scholar
  42. A.J.P. Van Heugten, M. Versluijs-Helder, H. Vromans, Elucidation of the variability in consistency of pharmacopoeia quality petrolatum. Drug Dev. Ind. Pharm. 43, 595–559 (2017)CrossRefGoogle Scholar

Copyright information

© AAPS (American Association of Pharmaceutical Scientists) 2019

Authors and Affiliations

  • Amy Ethier
    • 1
  • Padam Bansal
    • 2
  • James Baxter
    • 3
  • Nigel Langley
    • 1
  • Norman Richardson
    • 1
    Email author
  • Amitkumar Mavjibhai Patel
    • 2
  1. 1.BASF Pharma SolutionsTarrytownUSA
  2. 2.Amneal PharmaceuticalsPiscatawayUSA
  3. 3.LubrizolClevelandUSA

Personalised recommendations