Studies of intermolecular interactions in solid dispersions using advanced surface chemical analysis

Abstract

The aim of this study is to utilise an advanced surface chemical analysis based on X-ray photoelectron spectroscopy (XPS) to determine and characterise drug/polymer interactions in solid dispersions manufactured via hot melt extrusion (HME). Cetirizine HCl (CTZ) and verapamil HCl (VRP) were used as model cationic drugs while Eudragit® grade L100 and L100-55 polymers were used as anionic carriers. A molecular dynamics (MD) based simulation approach predicted drug/polymer interactions while scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS) mapping showed homogenous distribution of the drug particles onto the polymer matrices. Hot stage microscopy (HSM) characterised the solid state of the drugs in extruded formulations. XPS analysis revealed the strength and nature of interaction between the -NH 3 groups of the APIs with the -COOH groups of the polymers.The results obtained from XPS were supported by XRD and NMR studies. The estimation of non-protonated/ protonated N atom (N/N 0 ) ratios using XPS revealed the strength of the intermolecular interaction in drug/ polymer extrudates which can be used as an efficient tool to study the drug/polymer interaction.

RETRACTED: Evaluation of the surface chemistry and drug-polymer interaction of semi-crystalline micro-particles for the development of controlled release formulations

“…The calculated low N coefficient values in the formulations revealed that the interactions between the drug and polymers are quite strong. It has been reported that the lower N coefficient value leads to a high number of protonated N atoms that take part in the interactions making it stronger [27][28][29][30].…”

RETRACTED: Development and characterisation of semi-crystalline composite granules: The effect of particle chemistry and the electrostatic charging

“…Similar results were found in one of our previously reported study [20]. Moreover, EDS analysis was performed to map the distribution of IBU and homogeneity of the composite granules [24,25]. Both the drug and polymeric career used in this study mainly contain C and O atoms likewise most of the polymers.…”

The Effect of Cooling on the Degree of Crystallinity, Solid-State Properties, and Dissolution Rate of Multi-Component Hot-Melt Extruded Solid Dispersions

“…Maniruzzaman et al (2015) used the Flory-Huggins (F-H) lattice-based theory to explain intermolecular interactions between polymer and API is limited as it does not take into consideration the various multiple interactions in drug-polymer systems [20]. Therefore, the HSPs developed by Van Krevelen and Hoftyzer group were used as a substitute for the Flory-Huggins theory to explore the nature of interactions that occur within drug-polymer systems and is mainly based upon the chemical structures of each of the pure components.…”

“…where ∆G mix , ∆H mix , ∆S mix and T are the Gibbs free energy, enthalpy of mixing, entropy of mixing and absolute temperature, respectively. The free energy change is spontaneous as a result of the increase in entropy of mixing and is therefore negative [20]. However, the presence of repulsive and cohesive intermolecular and intramolecular forces (e.g., dispersion force, hydrogen bonding and dipole-dipole interaction) which are present within the amorphous SD, making the intermolecular interaction between drug and polymer more complex.…”

“…Calculated HSPs of and drug-polymer interaction factor for drug and polymers. Maniruzzaman et al (2015) prepared amorphous solid dispersions using hot-melt extrusion using the BCS class II drug Verapamil HCL, which had a molar attraction constant of 6.95 MPa 1/2 and reported that due to the high molar attraction constants of the APIs and polymeric carriers, they were able to contribute to hydrogen bonding [20]. As the HSPs are only theoretical, drug-polymer miscibility was further examined using various characterization, thermal analysis and solubility techniques to determine if the drug-polymer mixtures were miscible.…”