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. 2013 Sep;14(3):994-1003.
doi: 10.1208/s12249-013-9990-9. Epub 2013 Jun 18.

Design and evaluation of self-nanoemulsifying pellets of repaglinide

N S Desai  1 , M S Nagarsenker
Affiliations

Design and evaluation of self-nanoemulsifying pellets of repaglinide

N S Desai et al. AAPS PharmSciTech. 2013 Sep.

Abstract

The aim of study was to develop self-nanoemulsifying pellets (SNEP) for oral delivery of poorly water soluble drug, repaglinide (RPG). Solubility of RPG in oily phases and surfactants was determined to identify components of self-nanoemulsifying drug delivery system (SNEDDS). The surfactants and cosurfactants were screened for their ability to emulsify oily phase. Ternary phase diagrams were constructed to identify nanoemulsification area for the selected systems. SNEDDS formulations with globule size less than 100 nm were evaluated for in vivo anti-hyperglycemic activity in neonatal streptozotocin rat model. A significant reduction in glucose levels was produced by optimized SNEDDS formulation in comparison to the control group. The optimized SNEDDS formulations were pelletized via extrusion/spheronization technique using microcrystalline cellulose and lactose. SNEP were characterized by X-ray powder diffraction and scanning electron microscopy. X-ray diffraction study indicated loss of crystallinity of RPG in SNEP. The SNEP exhibited good flow properties, mechanical strength and formed nanoemulsion with globule size less than 200 nm. SNEP showed in vitro release of more than 80% RPG in 10 min which was significantly higher than RPG containing reference pellets. In conclusion, our studies illustrated that RPG, a poorly water soluble drug can be successfully formulated into SNEP which can serve as a promising system for the delivery of poorly water soluble drugs.

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Figures

Fig. 1
Fig. 1
Solubility of RPG in various oily phases. Data expressed as mean ± SD, n = 3
Fig. 2
Fig. 2
Solubility of RPG in various surfactants and cosurfactants. Data expressed as mean ± SD, n = 3
Fig. 3
Fig. 3
Ternary phase diagram of CP, CR and PEG 400 system
Fig. 4
Fig. 4
Ternary phase diagram of CP, SHS-15, Ac system
Fig. 5
Fig. 5
Effect of SNEDDS formulation on oral glucose tolerance test in rats. Value is expressed as mean ± SEM (n = 5), *significant with respect to control group, #significant with respect to RPG suspension treated group
Fig. 6
Fig. 6
XRD spectra of (a) F4 SNEP, (b) F6 SNEP, (c) reference RPG pellets, (d) RPG
Fig. 7
Fig. 7
Scanning electron micrographs of optimized SNEP
Fig. 8
Fig. 8
Comparison of dissolution profile of capsules filled with SNEP and reference RPG pellets
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