Design and development of microemulsion drug delivery system of atorvastatin and study its intestinal permeability in rats

Surjyanarayan Mandal, Snigdha S. Mandal, Krutika K. Sawant

Abstract


The objective of this study was to design and develop microemulsion drug delivery system of Atorvastatin and to investigate its intestinal transport behavior using the single-pass intestinal perfusion method in rat. Microemulsion drug delivery system of Atorvastatin was prepared by water titration method and optimized formulation was characterized. The permeability behavior of Atorvastatin over three different concentrations (10, 20 and 40 μg/mL) was studied in each isolated region of intestine (i.e. duodenum, jejunum, ileum and colon) of rat by single-pass intestinal perfusion method in rat method at a flow rate of 0.2 ml/min. The concentration of the sample was determined by HPLC and the effective permeability coefficients were calculated. Considering the high correlation of rat permeability coefficient values with those of human, the human intestinal permeability was predicted using the Lawrence compartment absorption and transit model. The intestinal permeability of Atorvastatin in microemulsion, plain drug suspension and marketed formulation was also compared. The particle size and zeta potential of Atorvastatin microemulsion were (18.2±0.3) nm and (–9.19±0.8) mV respectively. There was no significant difference in permeability coefficient in jejunum, duodenum and ileum with same concentration but higher in colon was observed. The permeability coefficient in jejunum at 10 μg/mL was significantly higher than that at 40 μg/mL (p< 0.01). The estimated human intestinal permeability of Atorvastatin for the microemulsion was relatively higher. Based on the above results, it could be concluded that microemulsion formulation could enhance the intestinal permeability of Atorvastatin and thus could be presented as a possible alternative to traditional oral formulations for improving the oral absorption of Atorvastatin.

Keywords: Microemulsion;, Zeta potential; Atorvastatin; Single-pass intestinal perfusion (SPIP) method; Compartment absorption and transit model (CAT)


Keywords


Microemulsion;, Zeta potential; Atorvastatin; Single-pass intestinal perfusion (SPIP) method; Compartment absorption and transit model (CAT)

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