Novel Gliclazide Electrosprayed Nano-Solid Dispersions: Physicochemical Characterization and Dissolution Evaluation.

Khosro Adibkia,Solmaz Ghajar,Shahram Emami,Niloufar Balaei,Mohammad Barzegar-Jalali,Karim Osouli-Bostanabad

doi:10.15171/apb.2019.026

Khosro Adibkia, Solmaz Ghajar + Show 4 more

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https://doi.org/10.15171/apb.2019.026

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Abstract

Purpose: In the current study, electrospraying was directed as a novel alternative approach to improve the physicochemical attributes of gliclazide (GLC), as a poorly water-soluble drug, by creating nanocrystalline/amorphous solid dispersions (ESSs). Methods: ESSs were formulated using Eudragit® RS100 and polyethylene glycol (PEG) 6000 as polymeric carriers at various drug: polymer ratios (i.e. 1:5 and 1:10) with different total solution concentrations of 10, 15, and 20% w/v. Morphological, physicochemical, and in-vitro release characteristics of the developed formulations were assessed. Furthermore, GLC dissolution behaviors from ESSs were fitted to various models in order to realize the drug release mechanism. Results: Field emission scanning electron microscopy analyses revealed that the size and morphology of the ESSs were affected by the drug: polymer ratios and solution concentrations. The polymer ratio augmentation led to increase in the particle size while the solution concentration enhancement yielded in a fiber establishment. Differential scanning calorimetry and powder X-ray diffraction investigations demonstrated that the ESSs were present in an amorphous state. Furthermore, the in vitro drug release studies depicted that the samples prepared employing PEG 6000 as carrier enhanced the dissolution rate and the model that appropriately fitted the release behavior of ESSs was Weibull model, where demonstrating a Fickian diffusion as the leading release mechanism. Fourier-transform infrared spectroscopy results showed a probability of complexation or hydrogen bonding, development between GLC and the polymers in the solid state. Conclusion: Hence the electrospraying system avails the both nanosizing and amorphization advantages, therefore, it can be efficiently applied to formulating of ESSs of BCS Class II drugs.

Highlights

One of the prevalent chronic metabolic disorders affecting seriously peoples’ health, is type II diabetes mellitus (T2DM), identified by pancreatic β-cell inadequate secretion of insulin and/or abnormal secretion of glucagon and/or tissue responses reduction to insulin.[1]
Corresponding to Field emission scanning electron microscopy (FE-SEM) images, it was recognized that the lower solution concentrations (i.e. 10 and 15% w/v) led to nanobeads/nanoparticles in a concave shape (Figure 1 (F1, F2, F4, F5)), whereas nanofibers formation resulted in the higher solution concentrations (i.e. 20% w/v) (Figure 1 (F3, F6))
Thermograms of electrosprayed samples (ESSs) prepared by using Eudragit® RS100 (Eudr) indicated the absence of GLC melting peak suggesting that GLC was entirely solubilized in the applied polymers, or its crystalline structure transformed to an amorphous state

Summary

Introduction

One of the prevalent chronic metabolic disorders affecting seriously peoples’ health, is type II (non-insulin dependent) diabetes mellitus (T2DM), identified by pancreatic β-cell inadequate secretion of insulin and/or abnormal secretion of glucagon and/or tissue responses reduction to insulin.[1]. Electrospraying (ECS)/electrospinning is a flexible approach with the potency of producing various formulations in the range of micro-nano size for a broad appeals scope in the pharmacy sector.[29,30] This economic, adjustable, and one-step system basically uses an electric power to atomize a polymer-drug solution In another word by imposing a high voltage electrical force, the polymer-drug solution droplets from a syringe will jet-out (atomize) and form micro/nano sized particles/ fibers on a grounded screen placed under the tip of the syringe.[25,31] The applied voltage, flow rate of the polymer-drug solution, and deposition distance as the system variables, surface tension, electrical conductivity, viscosity, and density as the polymer physical features, polymer to drug ratios and jetting behavior of the system (polymer-drug solution) are the affecting and controlling parameters that lead to nanofibers or nanoparticles (nanobeads) formation.[32,33]. In the present study Eudr and PEG 6000 were used as two appropriate candidates to prepare GLC NSDs conducting ECS method, with different drug to polymer ratios at various solution concentrations to enhance physicochemical characteristics of GLC

Materials and Methods

Results and Discussion

Conclusion