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AAPS PharmSciTech

, Volume 19, Issue 7, pp 3097–3109 | Cite as

Solid Form of Lipid-Based Self-Nanoemulsifying Drug Delivery Systems for Minimization of Diacerein Adverse Effects: Development and Bioequivalence Evaluation in Albino Rabbits

  • Mohamed Ahmed Naseef
  • Howida Kamal Ibrahim
  • Samia Abd El-Kader Nour
Research Article
  • 65 Downloads

Abstract

This work aimed to enhance the oral bioavailability of diacerein. The drug was incorporated in self-nanoemulsifying drug delivery system. Ternary phase diagrams were constructed using Capryol™90, Miglyol®812 and isopropyl myristate as oils, Tween®80 and Tween®20 as surfactants and PEG 200 and PEG 300 as co-surfactants. Among a total of 432 formulae, 17 formulae were clear. They were assessed for mean droplet size, polydispersity index (PDI), saturation solubility and transmission electron microscopy. Solid granules were obtained by adsorption on Aeroperl®300. Results for DSC, PXRD, and SEM of prepared granules revealed that diacerein was molecularly dispersed within the formula. Desirability factor was adopted to find the granules with maximum solubility, maximum dissolution efficiency, maximum dissolution rate and percentage of drug dissolved at 5 min and minimum dissolution time and Carr’s index. The optimized formula consisted of 10% Miglyol®812, 70% Tween®80 and 20% PEG 200 adsorbed to Aeroperl® 300 with a ratio of 2:1 preconcentrate:carrier. It recorded a 3.77-fold increase in bioavailability, compared to the marketed product. Such enhancement means lower doses and less gastrointestinal side effects.

KEY WORDS

diacerein self-nanoemulsifying granules bioavailability Aeroperl dissolution 

Abbreviations

BCS

Biopharmaceutics Classification System

SNEDDS

Self-nanoemulsifying drug delivery systems

SNEG

Self-nanoemulsifying granules

MDS

Mean droplet size

PDI

Polydispersity index

TEM

Transmission electron microscopy

DSC

Differential scanning calorimetry

FTIR

Fourier transform infrared spectroscopy

PXRD

Powder X-ray diffraction

SEM

Scanning electron microscopy

D.E.0–30

Dissolution efficiency 30 min

MDT

Mean dissolution time

Q5

Percentage of drug released at time 5 min

DR5

Dissolution rate during first 5 min of dissolution

REC

Research Ethics Committee

LC-MS/MS

Liquid chromatography–tandem mass spectrometry

IS

Internal standard

HLB

Hydrophilic–lipophilic balance

IPM

Isopropyl myristate

Notes

Compliance with Ethical Standards

The experiment protocol was accepted by the Research Ethics Committee of Faculty of Pharmacy, Cairo University, Cairo, Egypt (PI 911).

Conflict of Interest

The authors declare that there is no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Mohamed Ahmed Naseef
    • 1
  • Howida Kamal Ibrahim
    • 1
  • Samia Abd El-Kader Nour
    • 1
  1. 1.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyCairo UniversityCairoEgypt

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