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Pharmaceutical Product Characterization and Manufacturability of Surfactant-Enriched Oil Marbles with Abiraterone Acetate


The present study investigates the physicochemical properties and stability of a novel lipid-based formulation—surfactant-enriched oil marbles containing abiraterone acetate. While the biopharmaceutical performance of this formulation has been reported recently, this study aims to fill the gap between a promising in vivo performance and industrial applicability. A series of techniques were employed to assess the solid-state characteristics of oil marble cores along with their physicochemical properties upon stability testing. The chemical stability of abiraterone acetate in the formulation was also investigated. The core of the formulation was found to be stable both physically and chemically over 12 months of storage. The in vitro performance of stressed samples was evaluated using a dissolution experiment. The formulation has successfully self-emulsified upon incubation in bio-relevant media, resulting in a fast and complete API release. An important issue connected with the excipient used as a covering material of oil marbles has been identified. The seemingly insignificant water sorption caused agglomeration of the oil marbles and consequently compromised the dissolution rate in some of the stressed samples. Replacing HPMC with lactose as a covering material resulted in more favorable properties upon storage. Overall, it has been shown that oil marbles are an industrially applicable concept of the solidified lipid-based formulation.

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  1. Boyd BJ, Bergström CAS, Vinarov Z, Kuentz M, Brouwers J, Augustijns P, Brandl M, Bernkop-Schnürch A, Shrestha N, Préat V, Müllertz A, Bauer-Brandl A, Jannin V. Successful oral delivery of poorly water-soluble drugs both depends on the intraluminal behavior of drugs and of appropriate advanced drug delivery systems. Eur J Pharm Sci. 2019;137: 104967.

    Article  CAS  Google Scholar 

  2. Brouwers J, Brewster ME, Augustijns P. Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability? J Pharm Sci. 2009;98(8):2549–72.

    Article  CAS  Google Scholar 

  3. Mu H, Holm R, Müllertz A. Lipid-based formulations for oral administration of poorly water-soluble drugs. Int J Pharm. 2013;453(1):215–24.

    Article  CAS  Google Scholar 

  4. Gupta S, Kesarla R, Omri A. Formulation strategies to improve the bioavailability of poorly absorbed drugs with special emphasis on self-emulsifying systems. ISRN Pharmaceutics. 2013;2013: 848043.

    Article  Google Scholar 

  5. Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, Porter CJH. Strategies to address low drug solubility in discovery and development. Pharmacol Rev. 2013;65(1):315.

    Article  Google Scholar 

  6. Feeney OM, Crum MF, McEvoy CL, Trevaskis NL, Williams HD, Pouton CW, Charman WN, Bergström CAS, Porter CJH. 50years of oral lipid-based formulations: provenance, progress and future perspectives. Adv Drug Deliv Rev. 2016;101:167–94.

    Article  CAS  Google Scholar 

  7. Strickley RG, Currently marketed oral lipid-based dosage forms: drug products and excipients, 1st edition ed., Taylor & Francis Group (2007).

  8. Savla R, Browne J, Plassat V, Wasan KM, Wasan EK. Review and analysis of FDA approved drugs using lipid-based formulations. Drug Dev Ind Pharm. 2017;43(11):1743–58.

    Article  CAS  Google Scholar 

  9. Carrière F. Impact of gastrointestinal lipolysis on oral lipid-based formulations and bioavailability of lipophilic drugs. Biochimie. 2016;125:297–305.

    Article  Google Scholar 

  10. Bernkop-Schnürch A, Jalil A. Do drug release studies from SEDDS make any sense? J Control Release. 2018;271:55–9.

    Article  Google Scholar 

  11. Siqueira Jørgensen SD, Al Sawaf M, Graeser K, Mu H, Müllertz A, Rades T, The ability of two in vitro lipolysis models reflecting the human and rat gastro-intestinal conditions to predict the in vivo performance of SNEDDS dosing regimens, European Journal of Pharmaceutics and Biopharmaceutics 124 (2018) 116–124.

  12. Joyce P, Dening TJ, Meola TR, Schultz HB, Holm R, Thomas N, Prestidge CA. Solidification to improve the biopharmaceutical performance of SEDDS: opportunities and challenges. Adv Drug Deliv Rev. 2019;142:102–17.

    Article  CAS  Google Scholar 

  13. Dokania S, Joshi AK. Self-microemulsifying drug delivery system (SMEDDS)–challenges and road ahead. Drug Deliv. 2015;22(6):675–90.

    Article  CAS  Google Scholar 

  14. Jannin V, Musakhanian J, Marchaud D. Approaches for the development of solid and semi-solid lipid-based formulations. Adv Drug Deliv Rev. 2008;60(6):734–46.

    Article  CAS  Google Scholar 

  15. Shah AV, Serajuddin ATM. Development of solid self-emulsifying drug delivery system (SEDDS) I: use of Poloxamer 188 as both solidifying and emulsifying agent for lipids. Pharm Res. 2012;29(10):2817–32.

    Article  CAS  Google Scholar 

  16. Becker K, Salar-Behzadi S, Zimmer A. Solvent-free melting techniques for the preparation of lipid-based solid oral formulations. Pharm Res. 2015;32(5):1519–45.

    Article  CAS  Google Scholar 

  17. Shukla D, Chakraborty S, Singh S, Mishra B. Lipid-based oral multiparticulate formulations – advantages, technological advances and industrial applications. Expert Opin Drug Deliv. 2011;8(2):207–24.

    Article  CAS  Google Scholar 

  18. Boleslavská T, Rychecký O, Krov M, Žvátora P, Dammer O, Beránek J, Kozlík P, Křížek T, Hořínková J, Ryšánek P, Roušarová J, Canová NK, Šíma M, Slanař O, Štěpánek F. Bioavailability enhancement and food effect elimination of abiraterone acetate by encapsulation in surfactant-enriched oil marbles. AAPS J. 2020;22(6):122.

    Article  Google Scholar 

  19. Bormashenko E. Liquid marbles: properties and applications. Curr Opin Colloid Interface Sci. 2011;16(4):266–71.

    Article  CAS  Google Scholar 

  20. Ooi CH, Nguyen N-T. Manipulation of liquid marbles. Microfluid Nanofluid. 2015;19(3):483–95.

    Article  CAS  Google Scholar 

  21. European Medicines Agency, Zytiga European Public Assessment Report no. EMA/CHMP/542871, 2011.

  22. Acharya M, Bernard A, Gonzalez M, Jiao J, De Vries R, Tran N. Open-label, phase I, pharmacokinetic studies of abiraterone acetate in healthy men. Cancer Chemother Pharmacol. 2012;69(6):1583–90.

    Article  CAS  Google Scholar 

  23. Center for Drug Evaluation and Research, Clinical Pharmacology and Biopharmaceutics Review, NDA 202–379 Review – abiraterone acetate, 2011.

  24. Boleslavská T, Světlík S, Žvátora P, Bosák J, Dammer O, Beránek J, Kozlík P, Křížek T, Kutinová Canová N, Šíma M, Slanař O, Štěpánek F, Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH-induced precipitation, European Journal of Pharmaceutics and Biopharmaceutics 151 (2020) 81–90.

  25. Schultz HB, Meola TR, Thomas N, Prestidge CA. Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. Int J Pharm. 2020;577: 119069.

    Article  CAS  Google Scholar 

  26. Goldwater R, Hussaini A, Bosch B, Nemeth P, Comparison of a novel formulation of abiraterone acetate vs. the originator formulation in healthy male subjects: two randomized, open-label, crossover studies, Clinical Pharmacokinetics 56(7) (2017) 803–813.

  27. Food and Drug Administration, Drug Approval Package: YONSA (abiraterone acetate), appl. no. 210308, 2018.

  28. Stella VJ. Chemical drug stability in lipids, modified lipids, and polyethylene oxide-containing formulations. Pharm Res. 2013;30(12):3018–28.

    Article  CAS  Google Scholar 

  29. Shrestha H, Bala R, Arora S. Lipid-based drug delivery systems. J Pharm (Cairo). 2014;2014: 801820.

    Google Scholar 

  30. Douša M, Gibala P, Pekárek T. New approach of validation using internal normalization technique for quantification of related substances in raw material, intermediates and pharmaceutical substances by HPLC. J Pharm Biomed Anal. 2015;114:133–8.

    Article  Google Scholar 

  31. International Conference on Harmonisation: Stability Testing of New Drug Substances and Products, ICH Q1A(R2), ICH, 2003.

  32. Block ID, Scheffold F. Modulated 3D cross-correlation light scattering: improving turbid sample characterization. Rev Sci Instrum. 2010;81(12): 123107.

    Article  Google Scholar 

  33. Trunov D, Wilson JF, Ježková M, Šrom O, Beranek J, Dammer O, Šoóš M, Monitoring of particle sizes distribution during Valsartan precipitation in the presence of nonionic surfactant, Int J Pharm 600 (2021) 120515.

  34. Koppel DE, Analysis of macromolecular polydispersity in intensity correlation spectroscopy: the method of cumulants, J Chem Phys (57) (1972) 4814.

  35. Roger V, Cottet H, Cipelletti L. A new robust estimator of polydispersity from dynamic light scattering data. Anal Chem. 2016;88(5):2630–6.

    Article  CAS  Google Scholar 

  36. European Medicines Agency. European Pharmacopoeia 10.0. 2019.

  37. Cespi M, Bonacucina G, Misici-Falzi M, Golzi R, Boltri L, Palmieri GF. Stress relaxation test for the characterization of the viscoelasticity of pellets. Eur J Pharm Biopharm. 2007;67(2):476–84.

    Article  CAS  Google Scholar 

  38. Zhou D, Qiu Y, Understanding material properties in pharmaceutical product development and manufacturing: powder flow and mechanical properties, 2010.

  39. International Conference on Harmonisation: Validation of analytical procedures: text and Methodology ICH Q2(R1), ICH, 2005.

  40. International Conference on Harmonisation: Impurities in New Drug Products, ICH Q3B(R2). 2006.

  41. Krstić M, Medarević Đ, Đuriš J, Ibrić S, Chapter 12 - Self-nanoemulsifying drug delivery systems (SNEDDS) and self-microemulsifying drug delivery systems (SMEDDS) as lipid nanocarriers for improving dissolution rate and bioavailability of poorly soluble drugs, in: A.M. Grumezescu (Ed.), Lipid Nanocarriers for Drug Targeting, William Andrew Publishing2018, pp. 473–508.

  42. Stegemann S. Hard gelatin capsules today - and tomorrow. Bornem: Capsugel; 2002.

  43. Hoag SW, Chapter 27 - Capsules dosage form: formulation and manufacturing considerations, in: Y. Qiu, Y. Chen, G.G.Z. Zhang, L. Yu, R.V. Mantri (Eds.), Developing Solid Oral Dosage Forms (Second Edition), Academic Press, Boston, 2017, pp. 723-747.

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The authors would like to thank The Pharmaceutical Applied Research Centre (The PARC) and Zentiva k.s for supporting this work.


F.S. would like to acknowledge support by the Czech Science Foundation (project 19-26127X).

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Authors and Affiliations



J. Petřík: degradation products analysis, manuscript writing.

O. Rychecký: liquid marble formulation and processing, mechanical properties testing, flow properties testing, manuscript writing.

T. Boleslavská: dissolution tests, manuscript writing.

L. Becherová: spectroscopic analysis, manuscript writing.

D. Trunov: emulsion characterization, manuscript writing.

M. Prachár: liquid marble processing, mechanical properties testing, manuscript writing.

O. Navrátil: micro-CT analysis, manuscript writing.

P. Žvátora: liquid marble formulation, manuscript writing.

L. Krejčík: analytical method development, manuscript writing.

O. Dammer: DSC and XPRD analysis, manuscript writing.

J. Beránek: dissolution testing, manuscript writing.

P. Kozlík: analytical method development, manuscript writing.

T. Křížek: analytical method development, manuscript writing.

M. Šoóš: dynamic light scattering data interpretation, manuscript writing.

J. Heřt: analytical method development, manuscript writing.

S. Bissola: capsule filling experiments, manuscript writing.

S. Berto: capsule filling experiments, manuscript writing.

F. Štěpánek: conceptualization, supervision, funding acquisition, manuscript writing.

Corresponding author

Correspondence to František Štěpánek.

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Conflict of Interest

O. Rychecky is the owner of a start-up company MarbleMat, s.r.o., which develops liquid marble formulations. Other authors declare no competing financial interests.

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Petřík, J., Rychecký, O., Krejčí, T. et al. Pharmaceutical Product Characterization and Manufacturability of Surfactant-Enriched Oil Marbles with Abiraterone Acetate. AAPS PharmSciTech 23, 274 (2022).

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  • capsule filling
  • liquid marbles
  • SMEDDS formulation
  • solidification
  • stability