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Development and optimization of solid self-nanoemulsifying drug delivery system (S-SNEDDS) using Scheffe’s design for improvement of oral bioavailability of nelfinavir mesylate

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Abstract

The present research was aimed at development and evaluation of self-nanoemulsifying drug delivery system (SNEDDS) for improving bioavailability of nelfinavir mesylate (NFV), a protease inhibitor exhibiting pH dependent solubility and variable oral bioavailability. Maisine 35-1, Cremophor RH-40, and Labrasol were identified as oil, surfactant, and co-surfactant that had best solubility for NFV. Scheffe’s mixture design was used to optimize the amount of components in liquid self-nanoemulsifying drug delivery system (L-SNEDDS) by taking their amounts as independent variable, whereas globule size, drug loading, and percent transmittance were taken as dependent variable. Optimized NFV-L-SNEDDS was then adsorbed on Neusilin US2 to form solid self-nanoemulsifying drug delivery system (S-SNEDDS). NFV loaded L-SNEDDS and S-SNEDDS were characterized for various physicochemical properties, and solid-state properties were determined through differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy studies. In vitro dissolution using simulated gastric fluid and simulated intestinal fluid, ex vivo drug release study, and in vivo study were performed for pure NFV and NFV-S-SNEDDS. NFV-S-SNEDDS showed more than 90 % drug release in 20 min during drug release studies irrespective of pH of the dissolution medium. In vivo study revealed significant difference between release of NFV from suspension and NFV-L-SNEDDS and NFV-S-SNEDDS when given to rabbits (p < 0.001). NFV-L-SNEDDS and NFV-S-SNEDDS were subjected to stability study as per ICH guidelines, and NFV-S-SNEDDS was found to be stable during the period of study. S-SNEDDS could serve as a potential drug delivery system for NFV.

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Acknowledgments

The authors are thankful to Cipla Ltd. (Goa, India) for providing the gift sample of standard of Nelfinavir mesylate. The authors are also thankful to Abitec Corporation (OH, USA) Gattefosse (Lyon, France), and BASF (Ludwigshafen, Germany) for providing necessary excipients. The authors also express gratitude towards Mr. Punit Parejiya and Mr. Vinit Movaliya for helping in carrying out in vivo studies. It is a part of Ph.D. work carried out at Kadi Sarva Vishwavidyalaya (Gandhinagar, India). The authors express gratitude towards Gujarat Council on Science and Technology (GUJCOST) for funding the project under the scheme of Minor Research Project (MRP) having sanction order no. GUJCOST/MRP/201441/2009-10/3054.

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  1. K. B. Institute of Pharmaceutical Education and Research, Kadi Sarva Vishwavidyalaya, Gandhinagar, 382023, Gujarat, India

    Archita Patel, Pragna Shelat & Anita Lalwani

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Patel, A., Shelat, P. & Lalwani, A. Development and optimization of solid self-nanoemulsifying drug delivery system (S-SNEDDS) using Scheffe’s design for improvement of oral bioavailability of nelfinavir mesylate. Drug Deliv. and Transl. Res. 4, 171–186 (2014). https://doi.org/10.1007/s13346-014-0191-1

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