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

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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.

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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

Q 5 :

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

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, PO Box 11562, Cairo, Egypt

    Mohamed Ahmed Naseef, Howida Kamal Ibrahim & Samia Abd El-Kader Nour

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  1. Mohamed Ahmed Naseef
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  2. Howida Kamal Ibrahim
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  3. Samia Abd El-Kader Nour
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Corresponding author

Correspondence to Mohamed Ahmed Naseef.

Ethics declarations

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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Naseef, M.A., Ibrahim, H.K. & Nour, S.A.EK. Solid Form of Lipid-Based Self-Nanoemulsifying Drug Delivery Systems for Minimization of Diacerein Adverse Effects: Development and Bioequivalence Evaluation in Albino Rabbits. AAPS PharmSciTech 19, 3097–3109 (2018). https://doi.org/10.1208/s12249-018-1138-5

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