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AAPS PharmSciTech

, 20:82 | Cite as

Enhanced Oral Absorption of Amisulpride Via a Nanostructured Lipid Carrier-Based Capsules: Development, Optimization Applying the Desirability Function Approach and In Vivo Pharmacokinetic Study

  • Abd El-Halim I. El Assasy
  • Niha F. Younes
  • Amal I. A. MakhloufEmail author
Research Article
  • 59 Downloads

Abstract

Amisulpride (AMS), a second generation antipsychotic, suffers from low oral bioavailability (48%). This might be due to its pH-dependent solubility or being a substrate of P-glycoprotein efflux pump. Nanostructured lipid carriers (NLCs) were proposed in this study to enhance the oral absorption of AMS. AMS-NLCs were prepared by solvent evaporation technique according to (21.41.31) factorial design, whereas the type of solid lipid (tripalmitin or Gelucire® 43/1), lipid to drug ratio (7:1, 10:1, or 13:1) and type of external suspending medium (double distilled water, 0.5% TSP pH 12, 1% HPMC or 2.5% glycerin) were the independent variables. The average entrapment efficiency, particle size, polydispersity index, and zeta potential of the prepared formulations ranged from 29.01 to 69.06%, 184.9 to 708.75 nm, 0.21 to 0.59, and − 21 to − 33.55 mV, respectively. AMS-NLCs were optimized according to the desirability function to maximize the entrapment efficiency and minimize the particle size. Formulae G12, G10, and G7 with the highest desirability values of 0.915, 0.84, and 0.768, respectively, were chosen for further investigations. Novel AMS-NLCs capsules were prepared from the lyophilized formulations (TG7 and MG10) to enhance stability and increase patient compliance. The capsules were evaluated in terms of weight variation, content uniformity, and in vitro release pattern. The pharmacokinetics of AMS-NLCs capsules (formula TG7) were tested in rabbits compared to the commercial Amipride® tablets. The relative bioavailability of AMS-NLCs capsules was found to be 252.78%. In conclusion, the NLC-based capsules show potential to improve the oral bioavailability of AMS.

Key words

nanostructured lipid carriers amisulpride capsules oral drug delivery pharmacokinetics 

Abbreviations

AMS

Amisulpride

ANOVA

Analysis of variance

AUC(0-∞)

Area under plasma concentration-time curve extrapolated to infinity

CNS

Central nervous system

Cmax

Peak plasma concentration

DF

Desirability functions

DSC

Differential scanning calorimetry

DLS

Dynamic light scattering

DMSO

Dimethyl sulfoxide

ESM

External suspending medium

EE

Entrapment efficiency

FT-IR

Fourier-transform infrared

GIT

Gastrointestinal tract

HPMC

Hydroxypropyl methylcellulose

IS

Internal standard

K

Elimination rate constant

LC-MS/MS

Liquid chromatography-tandem mass spectroscopy

MRM

Multiple reaction monitoring

NLCs

Nanostructured lipid carriers

PS

Particle size

PDI

Polydispersity index

TSP

Tri-sodium ortho phosphate

TEM

Transmission electron microscopy

Tmax

Time to peak plasma concentration

XRD

X-ray diffractometry

Notes

Compliance with ethical standards

The study protocol was approved by the institutional review board; Research Ethics Committee-Faculty of Pharmacy, Cairo University (REC-FOPCU), Egypt, Serial No. (PI 1308).

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Abd El-Halim I. El Assasy
    • 1
  • Niha F. Younes
    • 1
  • Amal I. A. Makhlouf
    • 1
    Email author
  1. 1.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyCairo UniversityCairoEgypt

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