Unusual solubilization capacity of hydrophobic drug olanzapine in polysorbate micelles for improved sustained drug release

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

Volumetric, Viscometric and Spectroscopic Approach to Study the Solvation Behavior of Xanthine Drugs in Aqueous Solutions of NaCl at <i>T</i> = 288.15–318.15 K and at <i>p</i> = 101.325 kPa

The densities (ρ), viscosities (η), and ¹H nuclear magnetic resonance (NMR) studies for caffeine, theophylline, and theobromine in water and in aqueous solutions of 0.10, 0.25, 0.50, 0.75, and 1.00 mol·kg^–1 sodium chloride over a temperature range <i>T</i> = 288.15–318.15 K and at <i>p</i> = 101.325 kPa have been carried out using vibrating-tube digital densimeter, micro-Ubbelohde type capillary viscometer, and Bruker (AVANCE-III, HD 500 MHz) NMR spectrometer, respectively. From the density and viscosity data, apparent molar volume (<i>V</i>_2,ϕ), partial molar volume at infinite dilution (<i>V</i>_2,ϕ⁰), viscosity <i>B</i>-coefficient, corresponding transfer (Δ_tr<i>V</i>_2,ϕ⁰ and Δ_tr<i>B</i>) and other related parameters have been calculated. The trends in transfer parameters reveal the dominance of hydrophilic–ionic interactions at lower molalities of NaCl while hydrophobic–ionic interactions at higher molalities of NaCl. The expansibilities and d<i>B</i>/d<i>T</i> data show the structure-breaking behavior of theophylline and theobromine in water and in aqueous solutions of NaCl. However, behavior of caffeine is exceptional. The increase in chemical shift (δ) values with increasing molalities of NaCl also signifies the predominance of solute–cosolute interactions over the dehydration process. The results have further been discussed and rationalized in terms of various interactions