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Nanoparticle Engineering of Aprepitant Using Nano-by-Design (NbD) Approach

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Abstract

The aim of this research was to develop a nanosuspension of aprepitant (APT) using the Nano-by-Design approach. A novel microfluidization technology was used for processing the formulation. A 32 full factorial design was used for the optimization of dependent variables, which included critical quality attributes like particle size and polydispersity index. Subsequently, the design space was generated and the optimum formulation was located using desirability constraints followed by its validation.

The prepared nanosuspension had a particle size of 721 nm ± 5%, a polydispersity index of 0.106 ± 3%, and a zeta potential of − 8.06 ± 5 mV. Its surface morphology was studied using SEM, DSC, and XRD. It revealed that the prepared nanosuspension had a nano-crystalline nature. The process parameters did not lead to any physicochemical interaction between the drug and excipients. This was confirmed using FTIR analysis. In vitro dissolution studies revealed 100% cumulative drug release over 60 min, showing better results in comparison with pure APT. Thus, it has been shown that microfluidization can be an industrially feasible, novel, green technology for the preparation of a stable APT nanosuspension for improving the dissolution profile of the drug.

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Notes

  1. Aprepitant (APT), Scanning electron microscope (SEM), Differential scanning calorimetry, DSC and X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Active pharmaceutical ingredient (API).

References

  1. Lipinski C. Poor aqueous solubility - an industry wide problem in drug discovery. American Pharmaceutical Review. 2002;5:82–5.

    Google Scholar 

  2. Jain KK. The handbook of nanomedicine. Humana Press. 2008; 50.

  3. Khadka P, Ro J, Kim H, Kim I, Kim JT, Kim H, et al. Pharmaceutical particle technologies: an approach to improve drug solubility, dissolution and bioavailability. Asian J Pharm Sci. 2014;9:304–16.

    Article  Google Scholar 

  4. Nazlı H, Mesut B, Özsoy Y. In vitro evaluation of a solid supersaturated self nanoemulsifying drug delivery system (Super-SNEDDS) of aprepitant for enhanced solubility. Pharmaceuticals (Basel). 2021;14:1089.

    Article  Google Scholar 

  5. Roos C, Dahlgren D, Berg S, Westergren J, Abrahamsson B, Tannergren C, et al. In vivo mechanisms of intestinal drug absorption from aprepitant nanoformulations. Mol Pharm. 2017;14:4233–42.

    Article  CAS  Google Scholar 

  6. Kamboj S, Sharma R, Singh K, Rana V. Aprepitant loaded solid preconcentrated microemulsion for enhanced bioavailability: a comparison with micronized aprepitant. Eur J Pharm Sci. 2015 Oct 12;78:90–102. https://doi.org/10.1016/j.ejps.2015.07.008. 

  7. Bhandari PR. Recent advances in pharmacotherapy of chemotherapy-induced nausea and vomiting. J Adv Pharm Technol Res. 2012;3:202–9.

    Article  CAS  Google Scholar 

  8. Yeo S, An J, Park C, Kim D, Lee J. Design and characterization of phosphatidylcholine-based solid dispersions of aprepitant for enhanced solubility and dissolution. Pharmaceutics. 2020;12:E407.

    Article  Google Scholar 

  9. Bawa R. Nanopharmaceuticals: nanopharmaceuticals. Eur J Nanomed. 2010;3.

  10. Kakade P, Gite S, Patravale V. Development of atovaquone nanosuspension: quality by design approach. Curr Drug Deliv. 2020;17:112–25.

    Article  CAS  Google Scholar 

  11. Chogale M, Gite S, Patravale V. Comparison of media milling and microfluidization methods for engineering of nanocrystals: a case study. Drug Dev Ind Pharm. 2020;46:1763–75.

    Article  CAS  Google Scholar 

  12. Gite S, Kakade P, Patravale V. Surface engineering of fenofibrate nanocrystals using nano-by-design multivariate integration: a biopharmaceutical and pharmacokinetic perspective. Curr Drug Deliv. 2021;18:1314–29.

    Article  Google Scholar 

  13. Nekkanti V, Pillai R, Vabalaboina V. Drug nanoparticles - an overview. INTECH Open Access Publisher; 2012.

  14. Junghanns J-UAH, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomedicine. 2008;3:295–310.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Kalvakuntla S, Deshpande M, Attari Z, Kunnatur BK. Preparation and characterization of nanosuspension of aprepitant by H96 process. Adv Pharm Bull. 2016;6:83–90.

    Article  CAS  Google Scholar 

  16. Pramod K, Tahir MA, Charoo NA, Ansari SH, Ali J. Pharmaceutical product development: a quality by design approach. Int J Pharm Investig. 2016;6:129–38.

    Article  Google Scholar 

  17. Politis N, S, Colombo P, Colombo G, M Rekkas D. Design of experiments (DoE) in pharmaceutical development. Drug Dev Ind Pharm. 2017;43:889–901.

    Article  CAS  Google Scholar 

  18. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413–20.

    Article  CAS  Google Scholar 

  19. Kim M-S, Ha E-S, Choo G-H, Baek I-H. Preparation and in vivo evaluation of a dutasteride-loaded solid-supersaturatable self-microemulsifying drug delivery system. Int J Mol Sci. 2015;16:10821–33.

    Article  CAS  Google Scholar 

  20. Chogale MM, Ghodake VN, Patravale VB. Performance parameters and characterizations of nanocrystals: a brief review. Pharmaceutics, 2016; 8:26.

  21. Ren X, Qi J, Wu W, Yin Z, Li T, Lu Y. Development of carrier-free nanocrystals of poorly water-soluble drugs by exploring metastable zone of nucleation. Acta Pharm Sin B. 2019;9:118–27.

    Article  Google Scholar 

  22. Oktay AN, Karakucuk A, Ilbasmis-Tamer S, Celebi N. Dermal flurbiprofen nanosuspensions: Optimization with design of experiment approach and in vitro evaluation. Eur J Pharm Sci. 2018;122:254–63.

    Article  CAS  Google Scholar 

  23. Dizaj SM, Vazifehasl Zh, Salatin S, Adibkia Kh, Javadzadeh Y. Nanosizing of drugs: effect on dissolution rate. Res Pharm Sci. 2015;10:95–108.

    PubMed  PubMed Central  Google Scholar 

  24. Sun J, Wang F, Sui Y, She Z, Zhai W, Wang C, et al. Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals. Int J Nanomedicine. 2012;7:5733–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Kuehl C, El-Gendy N, Berkland C. NanoClusters surface area allows nanoparticle dissolution with microparticle properties. J Pharm Sci. 2014;103:1787–98.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors are thankful to Trident Equipments Pvt. Ltd. and Microfluidics for their facility as well as support.

The authors are also thankful to Mehta API Pvt. Ltd., Mumbai, India, for providing a gift sample of aprepitant.

The authors would like to acknowledge CII-SERB-India for providing Prime Minister’s Doctoral Fellowship to Pratik Kakade for his PhD work.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, 400019, India

    Pratik Kakade, Zubiya Pathan, Sandip Gite, Amit Mirani & Vandana B. Patravale

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  1. Pratik Kakade
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  2. Zubiya Pathan
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  3. Sandip Gite
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  5. Vandana B. Patravale
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Correspondence to Vandana B. Patravale.

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Kakade, P., Pathan, Z., Gite, S. et al. Nanoparticle Engineering of Aprepitant Using Nano-by-Design (NbD) Approach. AAPS PharmSciTech 23, 204 (2022). https://doi.org/10.1208/s12249-022-02350-5

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