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Development of Domperidone Solid Lipid Nanoparticles: In Vitro and In Vivo Characterization

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Abstract

Domperidone (DOP) is extensively applied orally in the management of nausea and vomiting. Upon oral administration, its bioavailability is very poor due to its poor solubility in alkaline media. Therefore, the aim of this work was to investigate DOP-loaded solid lipid nanoparticles (DOP-SLNs) in order to sustain its release pattern and to enhance oral bioavailability. DOP-SLNs were prepared using four different lipids. Prepared DOP-SLNs were characterized for “polydispersity index (PDI), particle size, zeta potential, % entrapment efficiency (% EE), and drug release behavior.” Differential scanning calorimetry (DSC) study was carried out to illustrate the physical form of DOP and excipients. The morphology of DOP-SLNs was confirmed by scanning electron microscopy (SEM). Pharmacokinetic study on optimized DOP-SLN in comparison to tablet was performed in rats. The “particle size, PDI, zeta potential, and % EE” of optimized formulation (F5) were recorded as 201.4 nm, 0.071, − 6.2 mV, and 66.3%, respectively. DSC thermograms suggested amorphous state of DOP in various SLNs. Surface morphology of SLNs using SEM suggested spherical shape of the nanoparticles within nanometer size range. In vitro release studies confirmed that all SLN formulations possessed a sustained release over a period of 12 h (51.3% from optimized formulation) in comparison with immediate release from conventional tablets (100% after 90 min). Pharmacokinetic study showed significant enhancement in oral absorption of DOP from optimized SLN in comparison with DOP tablet. The enhancement in relative bioavailability of DOP from optimized SLN was 2.62-fold in comparison with DOP tablet.

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References

  1. Gasco MR. Lipid nanoparticles: perspectives and challenges. Adv Drug Deliv Rev. 2007;59:377–8.

    Article  CAS  PubMed  Google Scholar 

  2. Mehnert W, Mader K. Solid lipid nanoparticles. Production, characterization and applications. Adv Drug Deliv Rev. 2001;47:165–96.

    Article  CAS  PubMed  Google Scholar 

  3. Bunjes H, Drechsler M, Koch MHJ, Westesen K. Incorporation of the model drug ubidecarenone into solid lipid nanoparticles. Pharm Res. 2001;18:287–93.

    Article  CAS  PubMed  Google Scholar 

  4. Muller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002;54:S131–55.

    Article  CAS  PubMed  Google Scholar 

  5. Ahmad N, Keith-Ferris J, Gooden E, Abell T. Making a case for domperidone in the treatment of gastrointestinal motility disorders. Curr Opin Pharmacol. 2006;6:571–6.

    Article  CAS  PubMed  Google Scholar 

  6. Silvers D, Kipnes M, Broadstone V, Patterson D, Quigley EM, McCallum R, et al. Domperidone in the management of symptoms of diabetic gastroparesis: efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. DOM-USA-5 Study Group. Clin Ther. 1998;20:438–53.

    Article  CAS  PubMed  Google Scholar 

  7. Shindler JS, Finnerty GT, Towlson K, Dolan AL, Davies CL, Parkes JD. Domperidone and levodopa in Parkinson’s disease. Br J Clin Pharmacol. 1984;18:959–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nagarsenker MS, Garad SD, Ramprakash G. Design, optimization and evaluation of domperidone coevaporates. J Control Release. 2000;63:31–9.

    Article  CAS  PubMed  Google Scholar 

  9. Reddymasu SC, Soykan I, McCallum RW. Domperidone: review of pharmacology and clinical applications in gastroenterology. Am J Gastroenterol. 2007;102:2036–45.

    Article  CAS  PubMed  Google Scholar 

  10. Patel DM, Patel SP, Patel CN. Formulation and evaluation of fast dissolving tablet containing domperidone ternary solid dispersion. Int J Pharm Investig. 2014;4:174–82.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Shailendra B, Shailendra M, Manish J, Singh TY, Priti T. Design and optimization of domperidone fast dissolving tablet using central composite design. Curr Drug Deliv. 2015;12:736–44.

    Article  CAS  PubMed  Google Scholar 

  12. Prajapati S, Patel L, Patel C. Floating matrix tablets of domperidone formulation and optimization using simplex lattice design. Iranian J Pharm Res. 2011;10:447–55.

    CAS  Google Scholar 

  13. Daraghmeh N, Chowdhry BZ, Leharne SA, Al-Omari MMH, Badwan AA. Co-processed chitin-mannitol as a new excipient for oro-dispersible tablets. Mar Drugs. 2015;13:1739–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yadav AV, Mote HH. Development of biodegradable starch microspheres for intranasal delivery. Indian J Pharm Sci. 2008;70:170–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Palem CR, Dudhipala NR, Battu SK, Repka MA, Rao YM. Development, optimization and in vivo characterization of domperidone-controlled release hot-melt-extruded films for buccal delivery. Drug Dev Ind Pharm. 2016;42:473–84.

    Article  CAS  PubMed  Google Scholar 

  16. Prabhu P, Shah S, Gundad S. Formulation development and investigation of domperidone transdermal patches. Int J Pharm Invest. 2011;1:240–6.

    Article  CAS  Google Scholar 

  17. Jakki R, Syed MA, Kandadi P, Veerabrahma K. Development of a self-microemulsifying drug delivery system of domperidone: in vitro and in vivo characterization. Acta Pharma. 2013;63:241–51.

    Article  CAS  Google Scholar 

  18. Patel R, Shah D. Nanoparticles loaded sublingual film as an effective treatment of chemotherapy induced nausea and vomiting. Int J Pharm Technol Res. 2015;8:77–87.

    CAS  Google Scholar 

  19. Thatipamula RP, Palem CR, Gannu R, Mudragada S, Yamsani MR. Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers. Daru. 2011;19:23–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Yassin AEB, Anwer MK, Mowafy HA, El-Bagory IM, Bayomi MA, Alsarra IA. Optimization of 5-fluorouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer. Int J Med Sci. 2010;7:398–408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Madishetti SK, Palem CR, Gannu R, Thatipamula RP, Panakanti PK, Yamsani MR. Development of domperidone bilayered matrix type transdermal patches: physicochemical, in vitro and ex vivo characterization. Daru. 2010;18:221–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Qi X, Qin J, Ma N, Chou X, Wu Z. Solid self-microemulsifying dispersible tablets of celastrol: formulation development, charaterization and bioavailability evaluation. Int J Pharm. 2014;472:40–7.

    Article  CAS  PubMed  Google Scholar 

  23. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22:659–61.

    Article  CAS  PubMed  Google Scholar 

  24. Klimkowska MB, Zywiec K, Poteulas A, Szutowski M. Impact of the changes in P-glycoprotein activity on domperidone pharmacokinetics in rat plasma. Pharmacol Rep. 2007;59:752–6.

    Google Scholar 

  25. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. New York: Marcel Dekker; 1982.

    Google Scholar 

  26. Venkateswarlu V, Manjunath K. Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles. J Control Release. 2004;95:627–38.

    Article  CAS  PubMed  Google Scholar 

  27. Torchilin V. Handbook of nanobiomedical research: fundamentals, applications and recent developments, vol. 1–4. World Scientific Publishing, Singapore, Hackensack (NJ), London, 2014.

  28. Doijad RC, Manvi FV, Godhwani DM, Joseph R, Deshmukh NV. Formulation and targeting efficiency of cisplatin engineered solid lipid nanoparticles. Indian J Pharm Sci. 2008;70:203–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gaumet M, Vargas A, Gurny R, Delie F. Nanoparticles for drug delivery: the need for precision in reporting particle size parameters. Eur J Pharm Biopharm. 2008;69:1–9.

    Article  CAS  PubMed  Google Scholar 

  30. Gupta M, Vyas SP. Development, characterization and in vivo assessment of effective lipidic nanoparticles for dermal delivery of fluconazole against cutaneous candidiasis. Chem Phys Lipids. 2012;165:454–61.

    Article  CAS  PubMed  Google Scholar 

  31. Varshosaz J, Minayian M, Moazen E. Enhancement of oral bioavailability of pentoxifylline by solid lipid nanoparticles. J Liposome Res. 2010;20:115–23.

    Article  CAS  PubMed  Google Scholar 

  32. Sanna V, Caria G, Mariani A. Effect of lipid nanoparticles containing fatty alcohols having different chain length on the ex vivo skin permeability of econazole nitrate. Powder Technol. 2010;201:32–6.

    Article  CAS  Google Scholar 

  33. Abbasalipourkabir R, Fallah M, Sedighi F, Maghsood AH, Javid S. Nanocapsulation of nitazoxanide in solid lipid nanoparticles as a new drug delivery system and in vitro release study. J Biol Sci. 2016;16:120–7.

    Article  CAS  Google Scholar 

  34. Kotikalapudi LS, Adepu L, Ratna JV, Diwan PV. Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles. Int J Pharm Biomed Res. 2012;3:22–9.

    CAS  Google Scholar 

  35. Dudhipala N, Janga KY. Lipid nanoparticles of zaleplon for improved oral delivery by Box–Behnken design: optimization, in vitro and in vivo evaluation. Drug Dev Ind Pharm. 2017;43:1205–14.

    Article  CAS  PubMed  Google Scholar 

  36. Kelidari HR, Saeedi M, Akbari J, Morteza-semnani K, Valizadeh H, Maniruzzaman M, et al. Development and optimisation of spironolactone nanoparticles for enhanced dissolution rates and stability. AAPS PharmSciTech. 2017;18:1469–74.

    Article  CAS  PubMed  Google Scholar 

  37. Assaf SM, Qandil AM, Al-Ani EA. Fast and pH-dependent release of domperidone from orally disintegrating tablets. Pharm Dev Technol. 2013;18:897–905.

    Article  CAS  PubMed  Google Scholar 

  38. Jain A, Jain SK. In vitro and cell uptake studies for targeting of ligand anchored nanoparticles for colon tumors. Eur J Pharm Sci. 2008;35:404–16.

    Article  CAS  PubMed  Google Scholar 

  39. Liu J, Hu W, Chen H, Ni Q, Xu H, Yang X. Isotretinoin-loaded solid lipid nanoparticles with skin targeting for topical delivery. Int J Pharm. 2007;328:191–5.

    Article  CAS  PubMed  Google Scholar 

  40. Rahman Z, Zidan S, Khan MA. Non-destructive methods of characterization of risperidone solid lipid nanoparticles. Eur J Pharm Biopharm. 2010;76:127–37.

    Article  CAS  PubMed  Google Scholar 

  41. Kushwaha AK, Vuddanda PR, Karunanidhi P, Singh SK, Singh S. Development and evaluation of solid lipid nanoparticles of raloxifene hydrochloride for enhanced bioavailability. Biomed Res Int. 2013;2013:E584549.

    Article  Google Scholar 

  42. Heykants J, Knaeps A, Meuldermans W, Michiels M. On the pharmacokinetics of domperidone in animals and man I. Plasma levels of domperidone in rats and dogs. Age related absorption and passage through the blood brain barrier in rats. Eur J Drug Metab Pharmacokinet. 1981;6:27–36.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

“The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding the work through research group project No. RGP-139.”

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia

    Gamal A. Shazly, Sultan Alshehri, Mohamed A. Ibrahim & Faiyaz Shakeel

  2. Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt

    Gamal A. Shazly, Hesham M. Tawfeek & Jelan A. Razik

  3. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Mutah University, Mutah, Karak, 61710, Jordan

    Hesham M. Tawfeek

  4. Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Dakhlia, Egypt

    Yasser A. Hassan

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  1. Gamal A. Shazly
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  2. Sultan Alshehri
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Correspondence to Faiyaz Shakeel.

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Shazly, G.A., Alshehri, S., Ibrahim, M.A. et al. Development of Domperidone Solid Lipid Nanoparticles: In Vitro and In Vivo Characterization. AAPS PharmSciTech 19, 1712–1719 (2018). https://doi.org/10.1208/s12249-018-0987-2

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  • DOI: https://doi.org/10.1208/s12249-018-0987-2

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