Development of Progesterone Oily Suspension Using Moringa Oil and Neusilin US2

Abstract

Purpose

The objective of the present study was to screen oils and suspending agents for the formulation of novel progesterone (PGT) suspension, demonstrating improved solubility, drug release, stability, and non-allergenicity. Presumably, formulated novel PGT suspensions could supersede clinically available peanut oil and lecithin based formulations (PL).

Method

The PGT suspensions were formulated by the trituration method using a vehicle (Moringa oil/peanut oil/sesame oil/sunflower oil) and a suspending agent (Neusilin US2/Fujicalin/Lecithin/Syloid 244) separately. A total of 16 PGT suspensions were evaluated for particle size, zeta potential, sedimentation, thixotropy, stability, in vitro dissolution, and allergenicity. Indeed, in silico studies were performed to elucidate interactions between principal components of the suspension, using software V. life MDS 4. 6.

Results

Findings revealed the highest PGT solubility and high viscosity in Moringa oil-based formulations. Suspensions comprising Moringa oil and Neusilin US2 (MN) exhibited the lowest suspensiod size (48.7 nm), least sedimentation rate, highest zeta potential (− 39.8), and dilatent flow behavior. The in vitro percent cumulative PGT dissolved was significantly high (94.82 ± 2.56%) from MN vis PL (52.68 ± 2.62%), at p < 0.05. In silico studies revealed strong hydrophobic and Van der Waals interactions between PGT, Moringa oil, and Neusilin US2, compared with others. Allergenicity study confirmed the superiority of Moringa oil over peanut oil (p < 0.01).

Conclusion

Moringa oil-based PGT formulations containing Neusilin US2 could be a better alternative to clinically available peanut oil and lecithin-based suspensions. Additionally, in silico interaction tools can be effectively employed for the prediction of stability and performance of suspensions.

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References

  1. 1.

    Al-Asmakh M. Reproductive functions of progesterone. Middle East Fertility Society Journal. 2007;12(3):147–52.

    Google Scholar 

  2. 2.

    Gadkar-Sable S, Shah C, Rosario G, Sachdeva G, Puri C. Progesterone receptors: various forms and functions in reproductive tissues. Front Biosci. 2005;10:2118–30. https://doi.org/10.2741/1685.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Posaci C, Smitz J, Camus M, Osmanagaoglu K, Devroey P. Progesterone for the luteal support of assisted reproductive technologies: clinical options. Hum Reprod. 2000;15(1):129–48. https://doi.org/10.1093/humrep/15.suppl_1.129.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Simon J. Introduction: an overview of progesterone and progestins. The J Fam Pract. 2007;(Suppl):3.

  5. 5.

    Malik S, Krishnaprasad K. Natural micronized progesterone sustained release (SR) and luteal phase: role redefined. J Clin Diagn Res. 2016;10(2):QE01–4. https://doi.org/10.7860/jcdr/2016/17278.7212.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Jain N, Tonpay SD, Jani A, Malviya S, Agrawal A. Natural progesterone: current approach for women’s health problem. International Journal of Pharmaceutical and Biological Activities. 2012;3(5):1025–7.

    Google Scholar 

  7. 7.

    Ciampagia W, Cognigni GE. Clinical use of progesterone in infertility and assisted reproduction. Acta Obstet Gynecol Scand. 2015;94:17–27. https://doi.org/10.1111/aogs.12770.

    CAS  Article  Google Scholar 

  8. 8.

    Tuleu C, Newton M, Rose J, Euler D, Saklatvala R. Comparative bioavailability study in dogs of a self-emulsifying formulation of progesterone presented in a pellet and liquid form compared with an aqueous suspension of progesterone. J Pharm Sci. 2004;93(6):1495–502. https://doi.org/10.1002/jps.20068.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Swarnakar NK, Jain V, Dubey V, Mishra D, Jain NK. Enhanced oromucosal delivery of progesterone via hexosomes. Pharm Res. 2007;24:2223–30. https://doi.org/10.1007/s11095-007-9409-y.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Jadhav NR, Irny PV, Patil US. Solid state behavior of progesterone and its release from NeusilinUS2 based liquisolid compacts. J Drug Delivery Sci Technol. 2017;38:97–106. https://doi.org/10.1016/j.jddst.2017.01.009.

    CAS  Article  Google Scholar 

  11. 11.

    Zoppetti G, Puppini N, Pizzutti M, Fini A, Giovani T, Comini S. Water soluble progesterone-hydroxypropyl-β-cyclodextrin complex for injectable formulations. J Incl Phenom Macrocycl Chem. 2007;57:283–8. https://doi.org/10.1007/s10847-006-9174-2.

    CAS  Article  Google Scholar 

  12. 12.

    Figueroa CE, Reider P, Burckel P, Pinkerton AA, Prud’homme RK. Highly loaded nanoparticulate formulation of progesterone for emergency traumatic brain injury treatment. Ther Deliv. 2012;3(11):1269–79. https://doi.org/10.4155/tde.12.115.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Cometti B. Pharmaceutical and clinical development of a novel progesterone formulation. Acta Obstet Gynecol Scand. 2015;94:28–37. https://doi.org/10.1111/aogs.12765.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Salem HF. Sustained-release progesterone nanosuspensions following intramuscular injection in ovariectomized rats. Int J Nanomed. 2010;5:943–54. https://doi.org/10.2147/ijn.s12947.

    CAS  Article  Google Scholar 

  15. 15.

    Mueller GA, Maleki SJ, Pedersen LC. The molecular basis of Peanut allergy. Curr Allergy and Asthma Rep. 2014;14:1–9. https://doi.org/10.1007/s11882-014-0429-5.

    CAS  Article  Google Scholar 

  16. 16.

    Palm M, Moneret-Vautrin DA, Kanny G, Denery-Papini S, Fremont S. Food allergy to egg and soy Lecithins. European J Allergy Clin Immunol. 1999;54(10):1116–7. https://doi.org/10.1034/j.1398-9995.1999.00305.x.

    CAS  Article  Google Scholar 

  17. 17.

    Catherine R, Catherine C, Christophe D. Allergy to soy Lecithin in a child. J Pediatr Gastroenterol. 1996;22(3):328–9. https://doi.org/10.1097/00005176-199604000-00019.

    Article  Google Scholar 

  18. 18.

    Prometrium. Product monograph. Merck Canada Inc. 2016;1–34. https://www.merck.ca/static/pdf/PROMETRIUM-PM_E.pdf. Accessed 10 December 2020

  19. 19.

    Cianferoni A, Muraro A. Food induced anaphylaxis. Immunol Allergy Clin N Am. 2012;32(1):165–95. https://doi.org/10.1016/j.iac.2011.10.002.

    Article  Google Scholar 

  20. 20.

    Taylor-Black S, Wang J. The prevalence and characteristic of food allergy in urban minority children. Ann Allergy Asthma Immunol. 2012;109(6):431–7. https://doi.org/10.1016/j.anai.2012.09.012.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Utrogestan (progesterone) formulation change—important information for patients with a peanut allergy. 2014. https://www.medsafe.govt.nz/safety/ews/2014/utrogestan-change.asp. Accessed 10 December 2020

  22. 22.

    PrReddy-Progesterone. Product monograph. Dr. Reddy’s Laboratories, Inc. 2018;1–35. https://www.drreddys.com/media/715873/english_pm-new.pdf. Accessed 10 December 2020

  23. 23.

    Phy JL, Weiss WT, Weiler CR, Damario MA. Hypersensitivity to progesterone-in-oil after in vitro fertilization and embryo transfer. Fertil Steril. 2003;80(5):1272–5. https://doi.org/10.1016/s0015-0282(03)01170-1.

    Article  PubMed  Google Scholar 

  24. 24.

    Orhevba BA, Sunmonu MO, Iwunze HI. Extraction and characterization of Moringa oleifera seed oil. Research and reviews: Journal of Food and Dairy Technology. 2013;1(1):22–7.

    Google Scholar 

  25. 25.

    Besins A, Besse J. Pharmaceutical composition based on micronized progesterone, preparation method & uses thereof. United States Patent Application Publication. 2011;1–5. https://patents.google.com/patent/US20110135719A1/en. Accessed 10 December 2020

  26. 26.

    Ji P, Yu T, Liu Y, Jiang J, Qui Y, Zhao W, Wu C. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake and pulmonary pharmacokinetics. Drug Des Devel Ther. 2016;10:911–25. https://doi.org/10.2147/dddt.s97738.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Antonopoulou E, Rohmann-Shaw CF, Sykes TC, Cayre OJ, Hunter TN, Jimack PK. Numerical and experimental analysis of the sedimentation of spherical colloid suspension under centrifugal force. Phys Fluids. 2018;30:1–12. https://doi.org/10.1063/1.5010735.

    CAS  Article  Google Scholar 

  28. 28.

    Ikarashi Y, Kaniwa M, Tsuchiya T. Sensitization potential of gold sodium thiosulfate in mice and guinea pigs. Biomaterials. 2002;23(24):4907–14. https://doi.org/10.1016/s0142-9612(02)00250-8.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Jacques D. Identification of contact allergens: the mouse ear sensitization assay. Cutan Ocul Toxicol. 2008;7:263–72. https://doi.org/10.3109/15569528809056306.

    Article  Google Scholar 

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Correspondence to Namdeo Jadhav.

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Jadhav, N., Pantwalawalkar, J., Sawant, R. et al. Development of Progesterone Oily Suspension Using Moringa Oil and Neusilin US2. J Pharm Innov (2021). https://doi.org/10.1007/s12247-020-09529-y

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Keywords

  • Progesterone
  • Moringa oil
  • Neusilin US2
  • Novel suspension