Self-Nano Emulsifying Powders (SNEPs) of Zaleplon with Neusilin®

Issue 27: OCTOBER 2012

Self-Nano Emulsifying Powders (SNEPs) of Zaleplon with Neusilin®

Ref: Karthik Y. Janga, Raju Jukanti, Sharath Sunkavalli, Ashok Velpula, Suresh Bandari, Prabhakar Kandadi and Prabhakar Reddy Veerareddy

Department of Pharmaceutics, St. Peter's Institute of Pharmaceutical Services, Hanamkonda, Warangal, Andhra Pradesh, India. Journal of Microencapsulation (2012)

INTRODUCTION

Enhancing the oral bioavailability of poorly water soluble drugs is one of the biggest challenges facing formulators. Solid dispersions and in particular Self-(nano)Emulsifying Drug Delivery Systems (SEDDS/SNEDDS) have proved to be the most practical route to commercialization. Successof Fortovase® (Saquinavir), Norvir® (Ritonavir) and Neoral® Cyclosporine) as lipid suspensions have prompted formulators to develop more stable forms by converting these suspensionsinto powder. Neusilin®'s high specific area, increased surface adsorption, porosity, anticaking, flow enhancing properties and its ability to keep the drug stable under amorphous state make
it one of the best choice among adsorbents available today.
Zaleplon (a nonbenzadiazepine sedative and hypnotic drug used in treatment of insomnia) has bioavailability of only 30%. Janga et al 2012 demonstrated that Zaleplon SNEP-Neusilin® powder formulation had higher predicted human permeability coefficient and percentage fraction oral dose adsorption in model systems.

The authors chose Neusilin® over Aerosil® 200, Maltodextrin and Pearlitol® SD200 due to it's improved performance.

SELF-NANO EMULSIFYING POWDERS (SNEPs)

Table 1. Flow properties of SNEP-N and other adsorbents

Z-SMEDDS was loaded on to 750 mg of adsorbents and evaluated to select the best carrier. Globule size, Polydispersity Index (PI) and zeta potential, the parameters critical for drug absorption of Zaleplon-SNEDDS were compared to SNEP-N.

Table 2. Mean size, zeta potential of Z-SNEDDS and reconstituted SNEP-N formulation

table2

Note: Each point represents mean ± SD ( n=3); PI: polydispersity index.

Z-SNEDDS : Zaleplon loaded SNEDDS; SNEP-N : Zaleplon loaded SNEDDS adsorbed onto Neusilin®

DISSOLUTION PROFILE
As shown in Figure 1, release of Zaleplon was over 80% in 60min and is significantly higher than 31% release from control.

Figure 1. In vitro dissolution profiles of Zaleplon from SNEP-N formulation and control (pure drug) (mean ± SD; n=3)

PHARMACOKINETIC STUDIES
The pharmacokinetic studies revealed that Cmax after treatment with SNEP-N formulation was significantly higher when compared to control formulation.

Figure 2. Pharmacokinetic profiles of Zaleplon in serum following oral administration of
SNEP-N formulation and control suspension (mean ± SD; n=6)

STABILITY OF SNEP-N
The SNEP-N is very stable free flowing powder even after storage at refrigerated temperature for 3 months (Figure 3). There was no change in colour, formation of emulsion globules after reconstitution was rapid without aggregation of molecules.

Figure 3. Stability profile of SNEP-N formulation with respect to globule size (nm) and zeta potential (mV) upon storage for 90 days at refrigerated temperature

CONCLUSIONS

Stable powder formulations of Zaleplon SNEDDS were successfully prepared using Neusilin® US2 as an adsorbent carrier. The performance of other common adsorbents like Aerosil® 200, Pearlitol® SD 200, Maltodextrin were inferior to that of Neusilin® US2.

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