Quality by Design Approach for Developing Lipid-Based Nanoformulations of Gliclazide to Improve Oral Bioavailability and Anti-Diabetic Activity

Abstract

The aim of the current investigation was to generate a self-nanoemulsifying drug delivery system (SNEDDS) of gliclazide (GCZ) to address the poor solubility and bioavailability. Ternary phase diagram was created with Capmul MCM C8 NF (oil), Cremophor RH 40 (surfactant), and Transcutol HP (co-surfactant) to distinguish the self-emulsifying region. A D-optimal design was employed with three variables, such as oil, surfactant, and co-surfactant, for further optimization of liquid (L)-SNEDDS. GCZ-loaded L-SNEDDs were analyzed for globule size, polydispersity index (PDI), and solubility. In vitro dissolution of optimized L-SNEDDS exhibited (F5) faster drug release (97.84%) within 30 min as compared to plain drug (15.99%). The optimized L-SNEDDS was converted to solid (S)-SNEDDS as a self-nanoemulsifying powder (SNEP) and pellets by extrusion-spheronization. Optimized S-SNEDDS were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In vitro dissolution of SNEP (S3) and pellet were 90.54 and 73.76%, respectively, at 30 min. In vivo studies showed a twofold rise in bioavailability through SNEDDS with a significant decline in blood glucose levels compared to plain drug suspension suggesting a lipid-based system as an alternative approach for treating diabetes.

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References

  1. 1.

    Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link? Biochem Pharmacol. 2006;72(11):1605–21.

    CAS  PubMed  Google Scholar 

  2. 2.

    Palmer KJ, Brogden RN. Gliclazide. Drugs. 1993;46(1):92–125.

    CAS  PubMed  Google Scholar 

  3. 3.

    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(3):413–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Desai KGH, Kulkarni AR, Aminabhavi TM. Solubility of rofecoxib in the presence of methanol, ethanol, and sodium lauryl sulfate at (298.15, 303.15, and 308.15) K. J Chem Eng Data. 2003;48(4):942–5.

    CAS  Google Scholar 

  5. 5.

    Delrat P, Paraire M, Jochemsen R. Complete bioavailability and lack of food-effect on pharmacokinetics of gliclazide 30 mg modified release in healthy volunteers. Biopharm Drug Dispos. 2002;23(4):151–7.

    CAS  PubMed  Google Scholar 

  6. 6.

    Bandarkar FS, Khattab IS. Lyophilized gliclazide poloxamer, solid dispersions for enhancement of in vitro dissolution and in vivo bioavailability. Int J Pharm Pharm Sci. 2011;3(2):122–7.

    CAS  Google Scholar 

  7. 7.

    Moyano J, Arias-Blanco M, Gines J, Giordano F. Solid-state characterization and dissolution characteristics of gliclazide-β-cyclodextrin inclusion complexes. Int J Pharm. 1997;148(2):211–7.

    CAS  Google Scholar 

  8. 8.

    Averineni RK, Shavi GV, Ranjan OP, Deshpande PB, Kumar GA, Nayak UY, et al. Formulation of gliclazide encapsulated chitosan nanoparticles: in vitro and in vivo evaluation. NanoFormulation. 2012;77–85.

  9. 9.

    Devarajan PV, Sonavane GS. Preparation and in vitro/in vivo evaluation of gliclazide loaded eudragit nanoparticles asa sustained release carriers. Drug Dev Ind Pharm. 2007;33:101–11.

    CAS  PubMed  Google Scholar 

  10. 10.

    Naik JBMV, Shevalkar GB, Patil KV, Patil JS, Yadava S, Verma U. Formulation and evaluation of poly (L-lactide-co-caprolactone) loaded gliclazide biodegaradable nanoparticles as a control release carrier. Int J Drug Deliv. 2013;5:300–8.

    Google Scholar 

  11. 11.

    Seo YG, Kim DH, Ramasamy T, Kim JH, Marasini N, Oh YK, et al. Development of docetaxel-loaded solid self-nanoemulsifying drug delivery system (SNEDDS) for enhanced chemotherapeutic effect. Int J Pharm. 2013;452(1):412–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Date AA, Desai N, Dixit R, Nagarsenker M. Self-nanoemulsifying drug delivery systems: formulation insights, applications and advances. Nanomedicine. 2010;5(10):1595–616.

    CAS  PubMed  Google Scholar 

  13. 13.

    Basalious EB, Shawky N, Badr-Eldin SM. SNEDDS containing bioenhancers for improvement of dissolution and oral absorption of lacidipine. I: development and optimization. Int J Pharm. 2010;391(1):203–11.

    CAS  PubMed  Google Scholar 

  14. 14.

    Inugala S, Eedara BB, Sunkavalli S, Dhurke R, Kandadi P, Jukanti R, et al. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for improved dissolution and oral bioavailability: in vitro and in vivo evaluation. Eur J Pharm Sci. 2015;74:1–10.

    CAS  PubMed  Google Scholar 

  15. 15.

    Woo JS, Song YK, Hong JY, Lim SJ, Kim CK. Reduced food-effect and enhanced bioavailability of a self-microemulsifying formulation of itraconazole in healthy volunteers. Eur J Pharm Sci. 2008;33(2):159–65.

    CAS  PubMed  Google Scholar 

  16. 16.

    Sharma D, Maheshwari D, Philip G, Rana R, Bhatia S, Singh M, et al. Formulation and optimization of polymeric nanoparticles for intranasal delivery of lorazepam using Box-Behnken design: in vitro and in vivo evaluation. Biomed Res Int. 2014;2014:1–14.

    Google Scholar 

  17. 17.

    Wankhade VP, Atram SC, Bobade NN, Pande SD, Tapar KK. Formulation and optimization of SNEDDS of gliclazide using response surface methodology. Asian J Pharm 2014;6(4).

  18. 18.

    Patel J, Patel A, Raval M, Sheth N. Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan. J Adv Pharm Technol Res. 2011;2(1):9–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Khan AW, Kotta S, Ansari SH, Sharma RK, Ali J. Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid naringenin: design, characterization, in vitro and in vivo evaluation. Drug Deliv. 2015;22(4):552–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Dash RN, Mohammed H, Humaira T, Reddy AV. Solid supersaturatable self-nanoemulsifying drug delivery systems for improved dissolution, absorption and pharmacodynamic effects of glipizide. J Drug Deliv Sci Technol. 2015;28:28–36.

    CAS  Google Scholar 

  21. 21.

    MaraMainardes LGM. Application of a validated HPLC-PDA method for the determination of melatonin content and its release from poly (lactic acid) nanoparticles. J Pharmaceut Anal. 2017;7(6):388–93.

    Google Scholar 

  22. 22.

    Craig D, Lievens H, Pitt K, Storey D. An investigation into the physico-chemical properties of self-emulsifying systems using low frequency dielectric spectroscopy, surface tension measurements and particle size analysis. Int J Pharm. 1993;96(1–3):147–55.

    CAS  Google Scholar 

  23. 23.

    Nazzal S, Khan MA. Response surface methodology for the optimization of ubiquinone self-nanoemulsified drug delivery system. AAPS PharmSciTech. 2002;3(1):23–31.

    PubMed Central  Google Scholar 

  24. 24.

    Pund S, Shete Y, Jagadale S. Multivariate analysis of physicochemical characteristics of lipid based nanoemulsifying cilostazol—quality by design. Colloids Surf B Biointerfaces. 2014;115:29–36.

    CAS  PubMed  Google Scholar 

  25. 25.

    Rahman MA, Iqbal Z, Hussain A. Formulation optimization and in vitro characterization of sertraline loaded self-nanoemulsifying drug delivery system (SNEDDS) for oral administration. J Pharm Investig. 2012;42(4):191–202.

    CAS  Google Scholar 

  26. 26.

    Kallakunta VR, Bandari S, Jukanti R, Veerareddy PR. Oral self-emulsifying powder of lercanidipine hydrochloride: formulation and evaluation. Powder Technol. 2012;221:375–82.

    CAS  Google Scholar 

  27. 27.

    Tarr BD, Yalkowsky SH. Enhanced intestinal absorption of cyclosporine in rats through the reduction of emulsion droplet size. Pharm Res. 1989;6(1):40–3.

    CAS  PubMed  Google Scholar 

  28. 28.

    Date AA, Nagarsenker M. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. Int J Pharm. 2007;329(1):166–72.

    CAS  PubMed  Google Scholar 

  29. 29.

    Gera S, Talluri S, Rangaraj N, Sampathi S. Formulation and evaluation of naringenin nanosuspensions for bioavailability enhancement. AAPS PharmSciTech. 2017;18(8):3151–62.

    CAS  PubMed  Google Scholar 

  30. 30.

    Neerati P, Bedada SK. Effect of diosmin on the intestinal absorption and pharmacokinetics of fexofenadine in rats. Pharmacol Rep. 2015;67(2):339–44.

    CAS  PubMed  Google Scholar 

  31. 31.

    Chavda H, Patel J, Chavada G, Dave S, Patel A, Patel C Self-nanoemulsifying powder of isotretinoin:preparation and characterization. J Powder Technol. 2013;2013.

  32. 32.

    Sunkavalli S, Eedara BB, Janga KY, Velpula A, Jukanti R, Bandari S. Preparation and characterization of docetaxel self-nanoemulsifying powders (SNEPs): a strategy for improved oral delivery. Korean J Chem Eng. 2015.

  33. 33.

    Abbaspour M, Jalayer N, Sharif Makhmalzadeh B. Development and evaluation of a solid self-nanoemulsifying drug delivery system for loratadin by extrusion-spheronization. Adv Pharm Bull. 2014;4(2):113–9.

    PubMed  Google Scholar 

  34. 34.

    Miao Y, Chen G, Ren L, Pingkai O. Characterization and evaluation of selfnanoemulsifying sustained-release pellet formulation of ziprasidone with enhancedbioavailability and no food effect. Drug Deliv. 2016;23(7):2163–72.

    CAS  PubMed  Google Scholar 

  35. 35.

    Elkordy AA, Essa EA, Dhuppad S, Jammigumpula P. Liquisolid technique to enhance and to sustain griseofulvin dissolution: effect of choice of non-volatile liquid vehicles. Int J Pharm. 2012;434(1):122–32.

    CAS  PubMed  Google Scholar 

  36. 36.

    Srikanth CH, Chaira T, Sampathi S, Sreekumar V, Bambal RB. Correlation of in vitro and in vivo plasma protein binding using ultracentrifugation and UPLC-tandem mass spectrometry. Analyst. 2013;138(20):6106–16.

    CAS  PubMed  Google Scholar 

  37. 37.

    Zawar LR, Bari SB. Preparation, characterization and in vivo evaluation of antihyperglycemic activity of microwave generated repaglinide solid dispersion. Chem Pharm Bull. 2012;60(4):482–7.

    CAS  PubMed  Google Scholar 

  38. 38.

    Sunkavalli S, Eedara BB, Janga KY, Velpula A, Jukanti R, Bandari S. Preparation and characterization of docetaxel self-nanoemulsifying powders (SNEPs): a strategy for improved oral delivery. Korean J Chem Eng. 2016;33(3):1115–24.

    CAS  Google Scholar 

  39. 39.

    Taha EI, Al-Saidan S, Samy AM, Khan MA. Preparation and in vitro characterization of self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate. Int J Pharm. 2004;285(1):109–19.

    CAS  PubMed  Google Scholar 

  40. 40.

    Constantinides PP, Scalart J-P, Lancaster C, Marcello J, Marks G, Ellens H, et al. Formulation and intestinal absorption enhancement evaluation of water-in-oil microemulsions incorporating medium-chain glycerides. Pharm Res. 1994;11(10):1385–90.

    CAS  PubMed  Google Scholar 

  41. 41.

    Porter CJ, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6(3):231–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Nielsen FS, Petersen KB, Müllertz A. Bioavailability of probucol from lipid and surfactant based formulations in minipigs: influence of droplet size and dietary state. Eur J Pharm Biopharm. 2008;69(2):553–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Gupta S, Chavhan S, Sawant KK. Self-nanoemulsifying drug delivery system for adefovir dipivoxil: design, characterization, in vitro and ex vivo evaluation. Colloids Surf A Physicochem Eng Asp. 2011;392(1):145–55.

    CAS  Google Scholar 

  44. 44.

    Zhao Y, Wang C, Chow AH, Ren K, Gong T, Zhang Z, et al. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of zedoary essential oil: formulation and bioavailability studies. Int J Pharm. 2010;383(1):170–7.

    CAS  PubMed  Google Scholar 

  45. 45.

    Takeuchi H, Nagira S, Yamamoto H, Kawashima Y. Solid dispersion particles of amorphous indomethacin with fine porous silica particles by using spray-drying method. Int J Pharm. 2005;293(1):155–64.

    CAS  PubMed  Google Scholar 

  46. 46.

    Balakrishnan P, Lee B-J, Oh DH, Kim JO, Hong MJ, Jee J-P, et al. Enhanced oral bioavailability of dexibuprofen by a novel solid self-emulsifying drug delivery system (SEDDS). Eur J Pharm Biopharm. 2009;72(3):539–45.

    CAS  PubMed  Google Scholar 

  47. 47.

    Newton M, Petersson J, Podczeck F, Clarke A, Booth S. The influence of formulation variables on the properties of pellets containing a self-emulsifying mixture. J Pharm Sci. 2001;90(8):987–95.

    CAS  PubMed  Google Scholar 

  48. 48.

    Bari A, Chella N, Sanka K, Shastri NR, Diwan PV. Improved anti-diabetic activity of glibenclamide using oral self-nanoemulsifying powder. J Microencapsul. 2015;32(1):54–60.

    CAS  PubMed  Google Scholar 

  49. 49.

    Mohd AB, Sanka K, Bandi S, Diwan PV, Shastri N. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of glimepiride: development and antidiabetic activity in albino rabbits. Drug Deliv. 2015;22(4):499–508.

    CAS  PubMed  Google Scholar 

  50. 50.

    Janga KY, Jukanti R, Sunkavalli S, Velpula A, Bandari S, Kandadi P, et al. In situ absorption and relative bioavailability studies of zaleplon loaded self-nanoemulsifying powders. J Microencapsul. 2013;30(2):161–72.

    CAS  PubMed  Google Scholar 

  51. 51.

    Gershanik T, Benita S. Self-dispersing lipid formulations for improving oral absorption of lipophilic drugs. Eur J Pharm Biopharm. 2000;50(1):179–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Rao SVR, Shao J. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: I. Formulation development. Int J Pharm. 2008;362(1):2–9.

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to acknowledge NIPER Hyderabad for providing facilities for the research work.

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Correspondence to Sunitha Sampathi.

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Patel, P., Pailla, S.R., Rangaraj, N. et al. Quality by Design Approach for Developing Lipid-Based Nanoformulations of Gliclazide to Improve Oral Bioavailability and Anti-Diabetic Activity. AAPS PharmSciTech 20, 45 (2019). https://doi.org/10.1208/s12249-018-1214-x

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KEY WORDS

  • D-optimal design
  • extrusion spheronization
  • SNEDDS
  • pharmacokinetics
  • single-pass intestinal perfusion
  • self-nanoemulsifying powder