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Optimization, in-vitro Release and in-vivo Evaluation of Gliquidone Nanoparticles

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Abstract

The present work embarks upon increasing the dissolution rate and the bioavailability of model anti-diabetic drug, gliquidone, a sulfonylurea class drug used for treating diabetes mellitus type 2. The gliquidone nanoparticles were prepared by using anti-solvent precipitation technique in which, gliquidone solution in acetone was added at a controlled rate to an aqueous solution containing polyvinylpyrrolidone K25 (PVP K25) as stabilizer. The effect of drug concentration (X1), polymer concentration (X2) and solvent to anti-solvent ratio (X3) on particle size and dissolution was studied using Box-Behnken design. The results revealed that by decreasing the drug concentration and by increasing the stabilizer concentration and solvent/anti-solvent ratio, reduction in the size of the particles was observed. The mentioned parameters were optimised and particle of size about 175 nm was achieved. The relative dissolution rate of prepared gliquidone nanoparticles in phosphate buffer pH 7.4 was ~ 4.7 times faster than original drug at t = 45 min. Further, the gliquidone nanoparticles were characterized by scanning electron microscope (SEM), Fourier transform-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). The particles revealed to be oval in shape with stabilizer molecules on surface and exhibited decreased crystalline nature when compared to free gliquidone. Finally, the in vivo studies using gliquidone nanoparticles revealed ~ 2.5-fold increase in Cmax when taken orally in the form of hard gelatin capsules in comparison to free gliquidone. Thus, overall investigation suggests that the developed strategy of gliquidone nanoparticles possess a keen potential for exhibiting anti-diabetic effect.

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References

  1. Arnouts P, Bolignano D, Nistor I, Bilo H, Gnudi L, Heaf J, et al. Glucose-lowering drugs in patients with chronic kidney disease: a narrative review on pharmacokinetic properties. Nephrology Dialysis Transplantation. 2013;29(7):1284–300.

    Google Scholar 

  2. Tripathi K. Essentials of medical pharmacology: JP Medical Ltd; 2013.

    Google Scholar 

  3. Miro A, Quaglia F, Sorrentino U, La Rotonda M, Bianca REDV, Sorrentino R. Improvement of gliquidone hypoglycaemic effect in rats by cyclodextrin formulations. Eur J Pharm Sci. 2004;23(1):57–64.

    CAS  PubMed  Google Scholar 

  4. Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN pharmaceutics. 2012;2012.

  5. Khames A. Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique. Drug delivery. 2017;24(1):328–38.

    CAS  PubMed  Google Scholar 

  6. Martnez P, Goñi M, Cantera R, Martin C, Dios-Viéitez C, Martínez-Ohárriz C. Preparation and dissolution rate of gliquidone-PVP K30 solid dispersions. Eur J Drug Metab Pharmacokinet. 1998;23(2):113–7.

    CAS  PubMed  Google Scholar 

  7. Sridevi S, Chauhan A, Chalasani K, Jain A, Diwan P. Enhancement of dissolution and oral bioavailability of gliquidone with hydroxy propyl-β-cyclodextrin. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 2003;58(11):807–10.

    CAS  Google Scholar 

  8. Patravale V, Date AA, Kulkarni R. Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol. 2004;56(7):827–40.

    CAS  PubMed  Google Scholar 

  9. Merisko-Liversidge EM, Liversidge GG. Drug nanoparticles: formulating poorly water-soluble compounds. Toxicol Pathol. 2008;36(1):43–8.

    CAS  PubMed  Google Scholar 

  10. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Kesisoglou F, Panmai S, Wu Y. Nanosizing—oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev. 2007;59(7):631–44.

    CAS  PubMed  Google Scholar 

  12. 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 Journal of Pharmaceutical Sciences. 2014;9(6):304–16.

    Google Scholar 

  13. Merisko-Liversidge E, Liversidge GG, Cooper ER. Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci. 2003;18(2):113–20.

    CAS  PubMed  Google Scholar 

  14. Fakes MG, Vakkalagadda BJ, Qian F, Desikan S, Gandhi RB, Lai C, et al. Enhancement of oral bioavailability of an HIV-attachment inhibitor by nanosizing and amorphous formulation approaches. Int J Pharm. 2009;370(1–2):167–74.

    CAS  PubMed  Google Scholar 

  15. Vimalson DC. Techniques to enhance solubility of hydrophobic drugs: an overview. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm. 2016;10(2).

  16. Yadav M, Dhole S, Chavan P. Nanosuspension: a novel techniques in drug delivery system. World Journal of Pharmacy and Pharmaceutical Sciences. 2014;3(2):410–33.

    CAS  Google Scholar 

  17. Krishna KB, Prabhakar C. A review on nanosuspensions in drug delivery. Int J Pharma and Bio Sci. 2011;2(1):549–58.

    Google Scholar 

  18. Li M, Azad M, Davé R, Bilgili E. Nanomilling of drugs for bioavailability enhancement: a holistic formulation-process perspective. Pharmaceutics. 2016;8(2):17.

    PubMed Central  Google Scholar 

  19. Keck CM, Müller RH. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. Eur J Pharm Biopharm. 2006;62(1):3–16.

    CAS  PubMed  Google Scholar 

  20. Matteucci ME, Hotze MA, Johnston KP, Williams RO. Drug nanoparticles by antisolvent precipitation: mixing energy versus surfactant stabilization. Langmuir. 2006;22(21):8951–9.

    CAS  PubMed  Google Scholar 

  21. Dong Y, Ng WK, Shen S, Kim S, Tan RB. Preparation and characterization of spironolactone nanoparticles by antisolvent precipitation. Int J Pharm. 2009;375(1–2):84–8.

    CAS  PubMed  Google Scholar 

  22. Reverchon E, De Marco I, Torino E. Nanoparticles production by supercritical antisolvent precipitation: a general interpretation. J Supercrit Fluids. 2007;43(1):126–38.

    CAS  Google Scholar 

  23. Thorat AA, Dalvi SV. Liquid antisolvent precipitation and stabilization of nanoparticles of poorly water soluble drugs in aqueous suspensions: recent developments and future perspective. Chem Eng J. 2012;181:1–34.

    Google Scholar 

  24. Kakran M, Sahoo G, Li L. Fabrication of nanoparticles of silymarin, hesperetin and glibenclamide by evaporative precipitation of nanosuspension for fast dissolution. Pharm Anal Acta. 2015;6(326):2.

    Google Scholar 

  25. Afifi SA, Hassan MA, Abdelhameed AS, Elkhodairy KA. Nanosuspension: an emerging trend for bioavailability enhancement of etodolac. International Journal of Polymer Science. 2015;2015.

  26. Xu Y, Liu X, Lian R, Zheng S, Yin Z, Lu Y, et al. Enhanced dissolution and oral bioavailability of aripiprazole nanosuspensions prepared by nanoprecipitation/homogenization based on acid–base neutralization. Int J Pharm. 2012;438(1–2):287–95.

    CAS  PubMed  Google Scholar 

  27. Kakran M, Sahoo NG, Li L, Judeh Z. Fabrication of quercetin nanoparticles by anti-solvent precipitation method for enhanced dissolution. Powder Technol. 2012;223:59–64.

    CAS  Google Scholar 

  28. El-Feky GS, Zayed G, Farrag A. Optimization of an ocular nanosuspension formulation for acyclovir using factorial design. Int J Pharm Pharm Sci. 2013;5:213–9.

    CAS  Google Scholar 

  29. Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123–33.

    CAS  PubMed  Google Scholar 

  30. Zayed G. Dissolution rate enhancement of Ketoprofen by surface solid dispersion with colloidal silicon dioxide. Unique Journal of Pharmaceutical and Biological Sciences. 2014;1:33–8.

    Google Scholar 

  31. Kakran M, Sahoo N, Li L, Judeh Z, Wang Y, Chong K, et al. Fabrication of drug nanoparticles by evaporative precipitation of nanosuspension. Int J Pharm. 2010;383(1–2):285–92.

    CAS  PubMed  Google Scholar 

  32. Giri TK. Manjusha (2013). Comparative in-vitro evaluation of conventional ibuprofen marketed formulation. J Pharm Sci Technol2(2):75–80.

  33. Helmy SA, El Bedaiwy HM. In vitro dissolution similarity as a surrogate for in vivo bioavailability and therapeutic equivalence. Dissolution Technologies. 2016;8:32–9.

    Google Scholar 

  34. Sridevi S, DIWAN PV. Validated HPLC method for the determination of gliquidone in rat plasma. Pharm Pharmacol Commun. 2000;6(7):303–7.

    CAS  Google Scholar 

  35. Zhang J, Brent Miller R, Russell S, Jacobus R. Validation of a stability-indicating HPLC method for the determination of dipyridamole in dipyridamole injection. J Liq Chromatogr Relat Technol. 1997;20(13):2109–21.

    CAS  Google Scholar 

  36. Guozhong C. Nanostructures and nanomaterials: synthesis, properties and applications: world scientific; 2004.

    Google Scholar 

  37. Pharmacopoeia B, Volume I. II-III. Cambridge, London: University Press; 2009.

    Google Scholar 

  38. Yeole B, Patil R, Lone K, Tekade A. Preparation of nanoparticles of poorly water soluble dronedarone by antisolvent addition technique using natural polymer as a stabilizer. Journal of Pharmaceutical Research and Clinical Practice. 2016;6(4):8.

    CAS  Google Scholar 

  39. Dalvi SV, Dave RN. Controlling particle size of a poorly water-soluble drug using ultrasound and stabilizers in antisolvent precipitation. Ind Eng Chem Res. 2009;48(16):7581–93.

    CAS  Google Scholar 

  40. Wang Y, Zheng Y, Zhang L, Wang Q, Zhang D. Stability of nanosuspensions in drug delivery. J Control Release. 2013;172(3):1126–41.

    CAS  PubMed  Google Scholar 

  41. Du B, Shen G, Wang D, Pang L, Chen Z, Liu Z. Development and characterization of glimepiride nanocrystal formulation and evaluation of its pharmacokinetic in rats. Drug delivery. 2013;20(1):25–33.

    CAS  PubMed  Google Scholar 

  42. Kakran M, Sahoo NG, Li L, Judeh Z. Particle size reduction of poorly water soluble artemisinin via antisolvent precipitation with a syringe pump. Powder Technol. 2013;237:468–76.

    CAS  Google Scholar 

  43. Nada A. Formulation of ibuprofen nanoparticles and nanosuspensions with enhanced dissolution rate using ultra-homogenization technique. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm. 2017;11(01).

  44. Kim S, Lee J. Effective polymeric dispersants for vacuum, convection and freeze drying of drug nanosuspensions. Int J Pharm. 2010;397(1–2):218–24.

    CAS  PubMed  Google Scholar 

  45. Lonare AA, Patel SR. Antisolvent crystallization of poorly water soluble drugs. International Journal of Chemical Engineering and Applications. 2013;4(5):337.

    CAS  Google Scholar 

  46. Wang Z, Chen J-F, Le Y, Shen Z-G, Yun J. Preparation of ultrafine beclomethasone dipropionate drug powder by antisolvent precipitation. Ind Eng Chem Res. 2007;46(14):4839–45.

    CAS  Google Scholar 

  47. Patel DD, Anderson BD. Adsorption of polyvinylpyrrolidone and its impact on maintenance of aqueous supersaturation of indomethacin via crystal growth inhibition. J Pharm Sci. 2015;104(9):2923–33.

    CAS  PubMed  Google Scholar 

  48. Shah SR, Parikh RH, Chavda JR, Sheth NR. Glibenclamide nanocrystals for bioavailability enhancement: formulation design, process optimization, and pharmacodynamic evaluation. J Pharm Innov. 2014;9(3):227–37.

    Google Scholar 

  49. Hintz RJ, Johnson KC. The effect of particle size distribution on dissolution rate and oral absorption. Int J Pharm. 1989;51(1):9–17.

    CAS  Google Scholar 

  50. Radtke M. Pure drug nanoparticles for the formulation of poorly soluble drugs. New Drugs. 2001;3(62–68).

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Acknowledgments

The authors are grateful to Faculty of Pharmacy, Al Azhar University, Assiut for providing the facilities. The authors are also thankful to Mianpharm pharmaceuticals, Egypt for supplying gliquidone and Chemical Industries Development, Egypt for providing capsules.

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt

    Mohamed S. Mohamed, Wael A. Abdelhafez & Gamal Zayed

  2. Al-Azhar Centre of Nanosciences and Applications, Al-Azhar University, Assiut, Egypt

    Gamal Zayed

  3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt

    Ahmed M. Samy

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  1. Mohamed S. Mohamed
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  2. Wael A. Abdelhafez
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Correspondence to Mohamed S. Mohamed.

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Mohamed, M.S., Abdelhafez, W.A., Zayed, G. et al. Optimization, in-vitro Release and in-vivo Evaluation of Gliquidone Nanoparticles. AAPS PharmSciTech 21, 35 (2020). https://doi.org/10.1208/s12249-019-1577-7

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