Aprepitant loaded solid preconcentrated microemulsion for enhanced bioavailability: A comparison with micronized Aprepitant

Abstract

Aprepitant (APT) is a lipophilic, poorly water soluble drug with moderate permeability characteristic. Therefore, we aimed to improve solubility as well as permeability that could possibly improve oral bioavailability of APT. For this purpose, Quality by design (QbD) approach employing simplex lattice mixture design was used to prepare solid preconcentrated microemulsion (S-PCM). Further, the software generated numerically optimized S-PCM formulations were developed by utilizing desirability function. The spectral attributes (powder X-ray diffraction, ATR-FTIR, and differential scanning calorimetry) of S-PCM formulations suggested that APT was present in amorphous form. The results of droplet size (150-180 nm), zeta potential (-13 to -15 mV), poly dispersity index (PDI) (0.211-0.238) and emulsification time (<1 min), of these S-PCM formulations (SP1, SP2 and SP3) suggested spherical shape morphology (Transmission electron microscopy) with thermodynamic stability. The comparison of in vitro/ex vivo behavior of S-PCM (SP1) with micronized and non-micronized formulations of APT suggested 2-fold and 5-fold enhancement in solubility and permeability, respectively. This was further evident from pharmacokinetic studies in rabbits that showed 1.5-fold enhancement in bioavailability of S-PCM with respect to micronized APT. Thus, it could be envisaged that development of S-PCM formulation of APT is the best alternative to micronization technology based APT formulations reported earlier.

Keywords: Apparent permeability; Oral bioavailability; Preconcentrated microemulsion (PCM); Simplex lattice design; Spray drying.