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Evaluation of niosome formulations containing methylene blue and cinnarizine manufactured by thin film hydration and microfluidic methods

Yeo, Li Key (2022) Evaluation of niosome formulations containing methylene blue and cinnarizine manufactured by thin film hydration and microfluidic methods. Doctoral thesis, University of Sunderland.

Item Type: Thesis (Doctoral)

Abstract

Enabling formulations has been emerging in formulation development owing to their characteristics to improve critical quality attributes of the drug delivery systems. This study focused on the preparation of niosome formulation as nanocarrier drug delivery system for the delivery of small drug molecules. This study was aimed to prepare niosome formulations to encapsulate cinnarizine, a poorly water-soluble drug with narrow absorption window in the stomach using the conventional thin film hydration (TFH) method and microfluidic (MF) method. Small drug molecule methylene blue was used as a model hydrophilic drug for optimisation of manufacturing and formulation parameters in order to pave the way for cinnarizine-containing niosome formulations.

The self-assembled niosomes were based on a 45/45/10 molar ratio of Span® 60 surfactant, cholesterol, and co-surfactant, respectively. Different drug-excipient ratios and different co-surfactant types (i.e. Cremophor® ELP, Cremophor® RH40 and Solutol® HS15) were investigated. Manufacturing variables in thin film hydration method were investigated, such as the hydration time and hydration volume. The effect of sonication on TFH-based niosomes was investigated. On the other hand, in microfluidic method, investigated manufacturing variables were total flow rate (mL/min) and flow rate ratio of the aqueous to organic solvents of the system parameters. Formulation parameters were drug concentration and total surfactant/lipid concentration. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were used to analyse the interactions between the model drug and formulation excipients. Additionally, the shape and size of all prepared niosome formulations were analysed using transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. The drug release characteristics of the formulations were evaluated using dialysis technique in 0.1M hydrochloric acid (pH1.2) at 37±1 °C under agitation. Determination and quantification of drug were obtained using high-performance liquid chromatography (HPLC) for encapsulation efficiencies and release data. Release data were analysed by fitting to release kinetic model to describe drug release behaviour. Stability studies of niosome formulations at a refrigeration temperature (2-8 °C) and room temperature (21-25 °C) for one month were evaluated for their size and distribution. The incorporation of different mucoadhesive polymers (chitosan solution and alginate-based Gaviscon® suspension) with MF-based niosomes were prepared to study their feasibility to adhere to gastric mucosa for prolonged retention of the formulation system containing drug with an absorption window in the stomach, in order to enhance drug absorption and bioavailability. A modified HPLC with evaporative light scattering detection (HPLC-ELSD) method was employed in the direct quantification of Span® 60 and cholesterol recovery of the MF-based niosomes before and after purification process (gel chromatography filtration), in order to understand the applicability on preparation of niosomes using microfluidics.

Generally, based on the size and distribution data, it was found that TFH-based niosome formulations showed large and highly polydisperse, comparing to MF-based niosome formulations. Niosome formulations released entrapped drug in a slow release pattern, offering a more consistent drug absorption with a prolonged gastric retention time. At the same time, mucoadhesive formulations have shown adhesion to the stomach mucosa, showing retentive potential for drug absorption. This study demonstrated and evaluated both the conventional TFH-based niosome and advanced MF-based niosome formulations encapsulating small drug molecules – cinnarizine (poorly water-soluble) and methylene blue (hydrophilic), offers insights on controlling manufacturing parameters to produce niosome formulations for their applicability as dosage forms.

Keywords: Niosome, methylene blue, cinnarizine, thin film hydration, microfluidics

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More Information

Depositing User: Veronique Laniel

Identifiers

Item ID: 14697
URI: http://sure.sunderland.ac.uk/id/eprint/14697

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Catalogue record

Date Deposited: 24 Mar 2022 15:57
Last Modified: 24 Mar 2022 16:00

Contributors

Author: Li Key Yeo

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Faculty of Health Sciences and Wellbeing

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