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Unusual solubilization capacity of hydrophobic drug olanzapine in polysorbate micelles

Updated: Mar 30

Polysorbates and Pluronic polymers are straightforward to use to improve the performance of hydrophobic molecules, however, colloidal systems of these polymers are not fully understood and loading of drug molecules in these Polysorbate micelles rely on a plethora of factors. Thus, it is a laborious task to select the optimal Polysorbate as a drug delivery vehicle. To pave the way for use of Polysorbates, three Polysorbates with different hydrophobicity were selected for oral delivery of the hydrophobic drug Olanzapine (OLZ). At higher concentration, Polysorbate T20 with low hydrophobicity accommodated a higher amount of OLZ than other Polysorbates T40 and T60 with higher hydrophobicity. The effect of mixed micelles of Pluronic P84 and Polysorbate (T20, T40, T60) on solubilization of OLZ was also studied at different concentration ratios and the higher OLZ solubilization was found to be in T20:P84 mixed micelles at 3:2 %w/v concentration ratio. Stronger interactions between OLZ and T20 were noticed with isothermal titration calorimetry (ITC), resulting in the higher OLZ solubilization in these micelles. Dynamic light scattering (DLS) and small angle neutron scattering (SANS) measurements revealed that mixed micelles of Polysorbates are greater in sizes than pure polysorbate micelles and the size decreased after loading of OLZ. Furthermore, SANS measurements suggested that decrease in the aggregation number after OLZ loading promoted the loading capacity of the Polysorbate micelle. Polysorbates micelles exhibited the sustained release behavior in biological relevant media, examined with in vitro dialysis release method. Therefore, it is believed that the finding of this work could be useful in the oral delivery formulations in which Polysorbates and Pluronics are primarily used.

Singla, P., Garg, S., Kaur, S., Kaur, N., Kaur, N., Aswal, V. K., ... & Mahajan, R. K. Unusual solubilization capacity of hydrophobic drug olanzapine in polysorbate micelles for improved sustained drug release. Journal of Molecular Liquids, 2022, 359, 119256.

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