AAPS PharmSciTech

, Volume 14, Issue 1, pp 78–85 | Cite as

Lyophilized Oral Sustained Release Polymeric Nanoparticles of Nateglinide

Research Article

Abstract

The objective of this study is to formulate lyophilized oral sustained release polymeric nanoparticles of nateglinide in order to decrease dosing frequency, minimize side effects, and increase bioavailability. Nateglinide-loaded poly Ɛ-caprolactone nanoparticles were prepared by emulsion solvent evaporation with ultrasonication technique and subjected to various studies for characterization including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, photon correlation spectroscopy and evaluated for in vitro drug release and pharmacodynamic studies. The influence of increase in polymer concentration, ultrasonication time, and solvent evaporation rate on nanoparticle properties was investigated. The formulations were optimized based on the above characterization, and the formulation using 5% polymer, 3-min sonication time, and rota-evaporated was found to have the best drug entrapment efficiency of 64.09 ± 4.27% and size of 310.40 ± 11.42 nm. Based on SEM, nanoparticles were found to be spherical with a smooth surface. In vitro drug release data showed that nanoparticles sustained the nateglinide release for over 12 h compared to conventional tablets (Glinate 60 mg), and drug release was found to follow Fickian mechanism. In vivo studies showed that nanoparticles prolonged the antidiabetic activity of nateglinide in rats significantly (p ≤ 0.05) compared to the conventional tablets (Glinate 60 mg) over a period of 12 h. Accelerated stability data indicated that there was minimal to no change in drug entrapment efficiency.

KEY WORDS

drug encapsulation efficiency nanoparticles poly Ɛ-caprolactone (PCL) probe sonication 

Notes

ACKNOWLEDGMENTS

The authors wish to thank Cadila Pharmaceuticals Ltd, Ahmadabad for providing them the drug sample. The authors also wish to thank Gland Pharma Ltd, Hyderabad for allowing them to carry out lyophilization studies in their facility.

REFERENCES

  1. 1.
    Krishna Reddy NV, Phani RSC, Rameshraju R. Validated RP-HPLC method for the estimation of nateglinide in formulation. Int J Res Pharm Chem. 2011;1(1):46–9.Google Scholar
  2. 2.
    McLeod JF. Clinical pharmacokinetics of nateglinide: a rapidly-absorbed, short-acting insulinotropic agent. Clin Pharmacokinet. 2004;43:97–120.PubMedCrossRefGoogle Scholar
  3. 3.
    Abdelwaheda W, Degoberta G, Stainmesseb S, Fessia H. Freeze-drying of nanoparticles: formulation, process and storage considerations. Adv Drug Deliv Rev. 2006;58:1688–713.CrossRefGoogle Scholar
  4. 4.
    Reis CP, Neufeld RJ, Ribeiro AJ, Veiga F. Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomedicine Nanotechnol Biol Med. 2006;2:8–21.CrossRefGoogle Scholar
  5. 5.
    Rieux Ad, Fievez V, Garinot M, Schneider Y-J, Préat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release. 2006;116:1–27.PubMedCrossRefGoogle Scholar
  6. 6.
    Galindo-Rodriguez SA, Allemann E, Fessi H, Doelker E. Polymeric nanoparticles for oral delivery of drugs and vaccines: a critical evaluation of in vivo studies. Crit Rev Ther Drug Carrier Syst. 2005;22:419–64.PubMedCrossRefGoogle Scholar
  7. 7.
    Sankalia JM, Sankalia MG, Sutariya VB, Mashru RC. Nateglinide quantification in rabbit plasma by HPLC: optimization and application to pharmacokinetic study. J Pharm Biomed Anal. 2007;44:196–204.PubMedCrossRefGoogle Scholar
  8. 8.
    Kim BK, Hwang SJ, Park JB, Park HJ. Characteristics of felodipine-located poly(ε-caprolactone) microspheres. J Microencapsul. 2005;22:193–203.PubMedCrossRefGoogle Scholar
  9. 9.
    Konan Y, Gurny R, Allemann E. Preparation and characterization of sterile and freeze dried sub-200 nm nanoparticles. Int J Pharm. 2002;233:239–52.PubMedCrossRefGoogle Scholar
  10. 10.
    Mainardes RM, Evangelista RC. PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution. Int J Pharm. 2005;290:137–44.PubMedCrossRefGoogle Scholar
  11. 11.
    Byuna Y, et al. Formulation and characterization of α-tocopherol loaded poly Ɛ-caprolactone (PCL) nanoparticles. LWT Food Sci Technol. 2011;44:24–8.CrossRefGoogle Scholar
  12. 12.
    Dhanalekshmi UM, Poovi G, Narra K, Neelakanta Reddy P. In vitro characterization and in vivo toxicity study of repaglinide loaded poly (methyl methacrylate) nanoparticles. Int J Pharm. 2010;396:194–203.CrossRefGoogle Scholar
  13. 13.
    Damgé C, Maincent P, Ubrich N. Oral delivery of insulin associated to polymeric nanoparticles in diabetic rats. J Control Release. 2007;117:163–70.PubMedCrossRefGoogle Scholar
  14. 14.
    Cuia F, Shia K, Zhanga L, Taoa A, Kawashima Y. Biodegradable nanoparticles loaded with insulin–phospholipid complex for oral delivery: preparation, in vitro characterization and in vivo evaluation. J Control Release. 2006;114:242–50.CrossRefGoogle Scholar
  15. 15.
    Thirupathi Reddy G, Ravi Kumar B, Krishna Mohan G, Ramesh M. Anithyperglycemic activity of Momordica dioica fruits in alloxan-induced diabetic rats. Asian J Pharmacodyn Pharmacokinet. 2006;6:327–9.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  1. 1.Department of Pharmaceutics, Sri Venkateshwara College of Pharmacy and Research CenterOsmania UniversityHyderabadIndia

Personalised recommendations