Design and evaluation of self-emulsifying drug delivery systems (SEDDS) of nimodipine

Abstract

The ability of self-emulsifying drug delivery systems (SEDDS) to improve solubility, dissolution rate and bioavailability of a poorly water-soluble calcium channel blocker, nimodipine (NM) was evaluated in the present investigation. Solubility of NM in various oils, surfactants and cosurfactants was determined. The influence of the ratio of oil to surfactant + cosurfactant, pH of aqueous phase on mean globule size of resulting emulsions was studied by means of photon correlation spectroscopy. The NM loaded SEDDS selected for the in vitro and in vivo studies exhibited globule size less than 180 nm. In vitro dissolution studies indicated that NM loaded SEDDS could release complete amount of NM irrespective of the pH of the dissolution media. Pharmacokinetics of NM suspension, NM oily solution, NM micellar solution and NM SEDDS were evaluated and compared in rabbits. Relative bioavailability of NM in SEDDS was significantly higher than all the other formulations. NM loaded SEDDS were subjected to various conditions of storage as per ICH guidelines for 3 months. NM SEDDS successfully withstood the stability testing.

Fig. 1

Solubility of NM in various oils; data expressed as mean ± SD (n = 3)

Fig. 2

Solubility of NM in various co-surfactants and surfactants; data expressed as mean ± SD (n = 3). Double asterisk Cosurfactant; asterisk surfactant

Fig. 3

Effect of O:SC ratio and pH of dilution medium on the mean globule size of various SEDDS (Mean globule size expressed as mean, n = 3, where relative standard deviation was <5%)

Fig. 4

Dissolution profiles SEDDS of NM in various dissolution media (Data expressed as mean, n = 3, where relative standard deviation was <5%)

Fig. 5

Plasma concentrations of NM after oral administration of various NM formulations to rabbits (n = 5). ^** P < 0.05 when compared to NM suspension