pH independent bi-layer Self-microemulsifying tablets ( SMETs) of Candesartan with Fujicalin ® and Neusilin ®

Issue 30: FEBRUARY 2013

pH independent bi-layer self-microemulsifying tablets (SMETs) of Candesartan cilexetil with Fujicalin^® and Neusilin^®

Ref: Yesung Sohn, Su Yeon Lee, Ga Hyeon Lee, Yeon-Joo Na, Seong Yeon Kim, Ilkyeong Seong, Beom-Jin Lee, Hyo-Jeong Kuh, Jaehwi Lee. Pharmaceutical Formulation Design Laboratory, College of Pharmacy, Chung-Aug University, Seoul; College of Pharmacy, Kangwon National University, Chuncheon; Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.

INTRODUCTION

Candesartan cilexetil (CDC), an angiotensin II receptor antagonist is a prodrug which gets converted to active drug Candersartan during absorption from the gastrointestinal tract. The conventional CDC tablets have a significantly low bioavailability of approximately 14% after oral administration.

Self-microemulsifying drug delivery system (SMEDDS) approach is becoming a common practice to enhance oral bioavailability of poorly water soluble drugs. To produce tablets of SMEDDS and to have a desired dissolution profile is considered one of the most difficult tasks for a formulator. Through several publications and commercial products, Neusilin^® and Fujicalin^® have proved to be one of the best adsorbent carriers available　in the industry today. In this newsletter, we summarized a recent study by Sohn et al. where a-pH-independent fast release bi-layer self-microemulsifying tablets (SMETs) of Candesartan cilexetil were prepared using Neusilin^® and Fujicalin^® as adsorbent carriers.

FORMULATION

The preparation was done in 2 steps.

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Table 1: Tableting formulation for development of self-microemulsifying tablets (SMET)
table1

DISSOLUTION PROFILE

Release of CDC from Fujicalin® SMET is comparable to CDC release from liquid SMEDDS (fig.1 ) in pH1.2. While release of CDC from Neusilin® UFL2 SMET is comparable to CDC release from liquid SMEDDS ( fig.2 ) in pH 6.5.

Fig. 1:

Dissolution profiles of CDC in SMETs in simulated gastric juice(pH 1.2)with 0.5% Tween^® 20. Data expressed as mean ± SD (n=3)

Fig. 2:

Dissolution profiles of CDC in SMETs in 0.05M phosphate buffer (pH 6.5)with 0.35% Tween^® 20. Data expressed as mean ± SD (n=3)

As seen in the above two graphs the release of CDC from Aeroperl^® 300 is comparatively low even though its specific surface area (300 m²/gm) is similar to that of Neusilin^® UFL2. This could be due to the entrapment of CDC in the pores of Aeroperl^®300 through which drug must migrate.

After understanding the dynamics of Fujicalin^® SMET and Neusilin^® UFL2 SMET, bi-layer tablet consisting of Fujicalin^® in first layer and Neusilin^® UFL2 in second layer was prepared. The composition of bi-layer was as mentioned in table 1. The dissolution profile of bi-layer SMET is as shown in fig.3.

Fig. 3:

Dissolution profiles of CDC in self-microemulsifying bi-layer tablets at different conditions (pH 1.2, pH 4.5 and pH 6.5) containing 0.35% Tween^®20.

Data are expressed as mean ± SD (n=3)

CONCLUSIONS

Fujicalin^® has high water adsorption capacity and erodes quickly at pH 1.2 thereby releasing CDC at the rate comparable to that of liquid SMEDDS. Whereas Neusilin^® UFL2 has very small particle size, high surface area and high oil adsorption capacity. The release of CDC at pH 6.5 from Neusilin^® UFL2 based SMET is comparable to that of liquid SMEDDS.

Thus by preparing bi-layer SMET of CDC with Fujicalin^® and Neusilin^® UFL2, it is possible to get immediate release of CDC which is independent of pH of GIT.

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