The Self-Assembly Phenomenon of Poloxamers and Its Effect on the Dissolution of a Poorly Soluble Drug from Solid Dispersions Obtained by Solvent Methods

Abstract

The self-assembly phenomenon of amphiphiles has attracted particular attention in recent years due to its wide range of applications. The formation of nanoassemblies able to solubilize sparingly water-soluble drugs was found to be a strategy to solve the problem of poor solubility of active pharmaceutical ingredients. Binary and ternary solid dispersions containing Biopharmaceutics Classification System (BCS) class II drug bicalutamide and either Poloxamer®188 or Poloxamer®407 as the surface active agents were obtained by either spray drying or solvent evaporation under reduced pressure. Both processes led to morphological changes and a reduction of particle size, as confirmed by scanning electron microscopy and laser diffraction measurements. The increase in powder wettability was confirmed by means of contact angle measurements. The effect of an alteration of the crystal structure was followed by powder X-ray diffractometry while thermal properties were determined using differential scanning calorimetry. Interestingly, bicalutamide exhibited a polymorph transition after spray drying with the poloxamer and polyvinylpyrrolidone (PVP), while the poloxamer underwent partial amorphization. Moreover, due to the surface activity of the carrier, the solid dispersions formed nanoaggregates in water, as confirmed using dynamic light scattering measurements. The aggregates measuring 200–300 nm in diameter were able to solubilize bicalutamide inside the hydrophobic inner parts. The self-assembly of binary systems was found to improve the amount of dissolved bicalutamide by 4- to 8-fold in comparison to untreated drug. The improvement in drug dissolution was correlated with the solubilization of poorly soluble molecules by macromolecules, as assessed using emission spectroscopy.

Data-Driven Modeling of the Bicalutamide Dissolution from Powder Systems

“…It leads to the conclusion that thermal analysis and its parameters, e.g., glass transition point (T g ), do not exhibit quantitative relationships with BCL dissolution patterns. This conclusion is consistent with the findings of Szafraniec et al (10) of the mechanism responsible for promotion of dissolution rate and extent of BCL in BCLpoloxamer (PLX) solid dispersions, which is not based completely on amorphization but on the solubilizing effect of Fig. 2.…”

“…Bicalutamide (BCL), a non-steroidal antiandrogen drug, exhibits aqueous solubility as low as 3.7 μg/mL and is well absorbed following oral administration (3,4), which classifies BCL to class II of the Biopharmaceutics Classification System (BCS) (5). Researchers reported in the literature improved dissolution of the powder systems with BCL by complexation with β-cyclodextrin (6,7), preparation of solid dispersions using solvent evaporation method (8)(9)(10)(11), milling (12,13), hot melt extrusion (14,15), and formation of co-amorphous systems (16). Desired dissolution improvement was achieved by trial and error approach, applying various qualitative, quantitative composition, and preparation methods under different conditions.…”

Poloxamer 338 Affects Cell Adhesion and Biofilm Formation in Escherichia coli: Potential Applications in the Management of Catheter-Associated Urinary Tract Infections

“…It is then possible to speculate that the adsorbed P388 was in a brush-like configuration promoted by the high hydrophobicity of silicone [23]. The brush-like configuration is the preferred one for our purposes since the hydrophilic PEO brushes could hinder bacterial adhesion by hydration and steric hindrance effects [24].…”

Multiparticulate Systems of Ezetimibe Micellar System and Atorvastatin Solid Dispersion Efficacy of Low-Dose Ezetimibe/Atorvastatin on High-Fat Diet-Induced Hyperlipidemia and Hepatic Steatosis in Diabetic Rats

“…The micellar systems MS-EZ (1:0.25) and MS-EZ (1:1) showed significant increases of 2.46- and 2.59-fold ( p < 0.05) at 10 min compared to EZ-RM ( Figure 4 A). Different studies indicated that surfactants such as Kolliphor RH40 or Tween 80 are especially suitable for the formation of micelles and increase the solubility of poorly solubility drugs [ 27 , 28 ]. The commercial tablet Ezetrol showed a release percentage of 75.52 ± 2.13% at 10 min.…”