pH Independent Bi-layer Self-microemulsifying Tablets (SMETs) of Candesartan Cilexetil with Fujicalin® and Neusilin®

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)

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 some of the best adsorbent carriers available in the industry today.

In this newsletter, we summarized a recent study by Sohn et al, Pharmazie 67: 917–924 (2012). 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.

STEP 1: PREPARATION OF SMEDDS
SMEDDS was prepared using Capryol90 , Tween 80, and tetragylcol in the ratio
5:35:60. This ratio was arrived at after several trials for dispersibility, solubilizing
capacity, smallest particle size of micro-emulsion and polydispersibility index (PDI).

STEP 2: PREPARATION OF SMET
SMEDDS was adsorbed on to solid carrier materials- Neusilin® UFL2, Fujicalin®, and
Aeroperl® 300. Tablets were prepared as per composition given in Table 1.

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

DISSOLUTION PROFILE

Release of CDC from Fujicalin® SMET is comparable to CDC release from liquid SMEDDS (fig.1 ) in pH 1.2. While release of CDC from Neusilin® UFL2 SMET is comparable to CDC release from liquid SMEDDS ( fig.2 ) in pH 6.5.

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) — **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/g) is similar to that of Neusilin® UFL2. This could be due to the entrapment of CDC in the pores of Aeroperl® 300 through which the drug must migrate.

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ｮ20. — **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ｮ20.

Fuji Chemicals

After understanding the dynamics of Fujicalin® SMET and Neusilin® UFL2 SMET, a bi-layer tablet consisting of Fujicalin® in the first layer and Neusilin® UFL2 in the second layer was prepared.

The composition of the bi-layer was as mentioned in Table 1. The dissolution profile of the bi-layer SMET is as shown in Fig. 3.

CONCLUSIONS

Fujicalin® has high water adsorption capacity and erodes quickly at pH 1.2, thereby releasing CDC at a rate comparable to that of liquid SMEDDS. Whereas Neusilin® UFL2 has a 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 the pH of GIT.

Continue reading and see the full Pharmaceutical Technical Newsletter on “pH Independent Bi-layer Self-microemulsifying Tablets (SMETs) of Candesartan Cilexetil with Fujicalin® and Neusilin®” here:

(click the picture to download the technical newsletter)