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Ageing as a Stabilising Process for Sustainable Dissolution Enhancement in a Carrier Tailored Atovaquone Electrospun
Xin Yi Teoh
Affiliation: Universiti Sains Malaysia
This study intends to investigate the performance of supersaturated atovaquone (ATQ) amorphous solid dispersion (ASD) electrospun systems after the ageing process, particularly the sustainable dissolution enhancement attained in the optimised freshly prepared electrospun samples.
Electrospun samples were maintained under accelerated condition (75% RH, 40°C) for 3 months and dry and temperate condition (0% RH, 25°C) and 12 months. Aged electrospun samples were analysed with polarised light microscopy, Attenuated Total Reflectance-Fourier Transform Infrared and Differential Scanning Calorimetry. Drug stability after the ageing process was determined via drug content assay using HPLC analysis. A non-sink condition was employed to study the dissolution performance of aged electrospun samples. Electrospun samples aged under accelerated condition recrystallised and completely reversed the advantage of ASD formulation in achieving supersaturation level, resulting in resembling raw ATQ in the drug release profile. In contrast, the electrospun sample aged under dry and temperate condition successfully preserved the sample amorphicity and exerted a positive effect in sustaining the dissolution enhancement. It was proposed that a dry storage condition avoided the moisture-induced recrystallisation, consequently allowing the amorphous content to structurally relax to its equilibrium glassy state through ageing. A more pronounced stabilising effect through ageing under dry and temperate condition was reported in the formulation with only hydrophilic components as carrier matrix (ES ATQ/K90) comparing the rest with hydrophobic components. This serves as an alternative method for stabilising the supersaturation achieved by ASD systems which was not previously achieved through the optimisation of the hydrophilic-hydrophobic balance of the polymeric carrier system.
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