Solid Self Emulsifying DDS of Paliperidone with Neusilin®

Issue 28: NOVEMBER 2012

Solid Self Emulsifying DDS of Paliperidone with Neusilin®

Ref: Swetha Kanuganti, Raju Jukanti, Prabhakar R. Veerareddy, and Suresh Bandari
Department of Pharmaceutics, St. Peter's Institute of Pharmaceutical Sciences, Warangal, Andhra Pradesh, India

INTRODUCTION
Self-Emulsifying Drug Delivery Systems (SEDDS) have proved to be the promising technology for improving bioavailability of poorly water soluble drugs. The commercialization of a few SEDDS such as Fortovase (saquinavir), Norvir (Ritonavir), and Neoral (cyclosporine) established interest in the commercial viability of these formulation systems. To overcome some complications in SEDDS, the liquid SEDDS are adsorbed on to inert carriers to produce solid SEDDS.
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 carriers today.
Paliperidone (9-hydroxyrisperidone, an active metabolite of risperidone a second-generation antipsychotic for the treatment of schizophrenia) has limited bioavailability of 28%.
Paliperidone loaded SEDDS was formulated into solid SEDDS by adsorbing on to Neusilin® as carrier. The in vitro dissolution study indicates improved dissolution characteristics with higher dissolution efficiency for solid SEDDS (SEDDS-N) compared to pure drug.

SOLID SEDDS (SEDDS-N)

POWDER PROPERTIES OF SOLID SEDDS (SEDDS-N)
Free flowable powder of SEDDS-N was obtained using Neusilin® (500 mg per g of SEDDS formulation). The angle of repose value was 31.62° which indicates good flowability. XRD studies were performed to confirm the physical nature of the drug in the solid SEDDS (Figure 1). The X-ray powder diffractogram of Paliperidone show intense peaks due to the native crystalline form of the drug. The disappearance of peaks in SEDDS-N clearly indicates the conversion of Paliperidone to amorphous or molecular form.

Figure 1. X-ray powder diffraction spectra of Paliperidone, SEDDS-N formulation, and Neusilin®

DISSOLUTION PROFILE
The drug release was faster and the dissolution efficiency was higher for the solid SEDDS compared to crystalline form. Cumulative percentage release from solid SEDDS was found to be 94.0 ± 7.1% within 60 minutes and was significantly higher than the control (29.08 ± 0.9%).

Figure 2. In vitro dissolution profiles of solid SEDDS (SEDDS-N) and control (paliperidone powder) (Mean ± SD; n = 3)

EX VIVO PERMEATION STUDY
Ex vivo permeation studies carried out using rat intestine suggests a 2- to 3-fold improvement in permeation for SEDDS compared to pure drug (Figure 3).

Figure 3. Ex vivo permeation profiles of various SEDDS formulation across rat intestine (Mean ± SD; n = 3)

CONCLUSIONS

Solid SEDDS of Paliperidone was successfully prepared using Neusilin® US2 as an adsorbent carrier. The in vitro dissolution study and ex vivo permeation study indicate that the SEDDS-N proves to be potential system for improved oral bioavailability of Paliperidone.

Neusilin® is a trademark or registered trademark of Fuji Chemical Industry Co., Ltd in Japan, United States of America, Europe and/or other countries.

To ensure to receive this newsletter in your inbox, please add pharma@fujichemical.co.jp to your address book.

The information found in this publication is presented in good faith with no guarantee or obligation as to accuracy and no assumption of liability. Users should make their own tests to determine the suitability of these products for their own particular purposes. However, because of numerous factors affecting results, Fuji Chemical Industry makes no warranty of any kind, express or implied, including those of merchantability and fitness for particular purpose other than the material conforms to its applicable current standard specifications. Statements concerning the use of the products or formulations described herein are not to be construed as recommending the infringement of any patent and seller assumes no liability for the infringement arising out of such use.