Interactions In Solid Dispersions Research Articles

Ammonio Methacrylate Copolymer (Type B)-Diltiazem Interactions in Solid Dispersions and Microsponge Drug-Delivery Systems.

This paper presents a complex analytical study on the distribution, solubility, amorphization, and compatibility of diltiazem within the composition of Eudragit RS 100-based particles of microspongeous type. For this purpose, a methodology combining attenuated total reflectance Fourier transform infrared (ATR-FTIR) absorption spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy with energy-dispersive X-ray microanalysis (SEM-EDX), and in vitro dissolution study is proposed. The correct interpretation of the FTIR and drug-dissolution results was guaranteed by the implementation of two contrasting reference models: physical drug–polymer mixtures and casting-obtained, molecularly dispersed drug–polymer composites (solid dispersions). The spectral behavior of the drug–polymer composites in the carbonyl frequency (νCO) region was used as a quality marker for the degree of their interaction/mutual solubility. A spectral-pattern similarity between the microsponge particles and the solid dispersions indicated the molecular-type dispersion of the former. The comparative drug-desorption study and the qualitative observations over the DSC and SEM-EDX results confirmed the successful synthesis of a homogeneous coamorphous microsponge-type formulation with excellent drug-loading capacity and “controlled” dissolution profile. Among them, the drug-delivery particles with 25% diltiazem content (M-25) were recognized as the most promising, with the highest population of drug molecules in the polymer bulk and the most suitable desorption profile. Furthermore, an economical and effective analytical algorithm was developed for the comprehensive physicochemical characterization of complex delivery systems of this kind.

Molecular Interactions in Solid Dispersions of Poorly Water-Soluble Drugs

Physicochemical characterization is a crucial step for the successful development of solid dispersions, including the determination of drug crystallinity and molecular interactions. Typically, the detection of molecular interactions will assist in the explanation of different drug performances (e.g., dissolution, solubility, stability) in solid dispersions. Various prominent reviews on solid dispersions have been reported recently. However, there is still no overview of recent techniques for evaluating the molecular interactions that occur within solid dispersions of poorly water-soluble drugs. In this review, we aim to overview common methods that have been used for solid dispersions to identify different bond formations and forces via the determination of interaction energy. In addition, a brief background on the important role of molecular interactions will also be described. The summary and discussion of methods used in the determination of molecular interactions will contribute to further developments in solid dispersions, especially for quick and potent drug delivery applications.

Solid-State Spectroscopic Investigation of Molecular Interactions between Clofazimine and Hypromellose Phthalate in Amorphous Solid Dispersions.

It has been technically challenging to specify the detailed molecular interactions and binding motif between drugs and polymeric inhibitors in the solid state. To further investigate drug-polymer interactions from a molecular perspective, a solid dispersion of clofazimine (CLF) and hypromellose phthalate (HPMCP), with reported superior amorphous drug loading capacity and physical stability, was selected as a model system. The CLF-HPMCP interactions in solid dispersions were investigated by various solid state spectroscopic methods including ultraviolet-visible (UV-vis), infrared (IR), and solid-state NMR (ssNMR) spectroscopy. Significant spectral changes suggest that protonated CLF is ionically bonded to the carboxylate from the phthalyl substituents of HPMCP. In addition, multivariate analysis of spectra was applied to optimize the concentration of polymeric inhibitor used to formulate the amorphous solid dispersions. Most interestingly, proton transfer between CLF and carboxylic acid was experimentally investigated from 2D 1H-1H homonuclear double quantum NMR spectra by utilizing the ultrafast magic-angle spinning (MAS) technique. The molecular interaction pattern and the critical bonding structure in CLF-HPMCP dispersions were further delineated by successfully correlating ssNMR findings with quantum chemistry calculations. These high-resolution investigations provide critical structural information on active pharmaceutical ingredient-polymer interaction, which can be useful for rational selection of appropriate polymeric carriers, which are effective crystallization inhibitors for amorphous drugs.

An investigation of nifedipine miscibility in solid dispersions using Raman spectroscopy.

Raman spectroscopy is potentially an extremely useful tool for the understanding of drug-polymer interactions in solid dispersions. This is examined and demonstrated for the case of solid dispersions of nifedipine in a polymeric substrate. Solid dispersions consisting of nifedipine and polyvinyl caprolactam--polyvinyl acetate--polyethylene glycol graft copolymer (Soluplus®) were prepared by freeze drying, melting and solvent evaporation at drug loadings of 10, 30, 50, 70 and 90% w/w. Drug-polymer interactions in the amorphous solid dispersion were estimated by Raman spectroscopy. The correlation between the solid state stability of the drug in a solid dispersion and the extent of drug-polymer interaction was monitored by X-ray diffractometry. The miscibility limit of nifedipine-Soluplus® was found to be 30% w/w drug loading for all preparation methods. The drug was found to interact with Soluplus®, through a hydrophilic interaction identified by infrared spectroscopy and a hydrophobic interaction which could be quantified by Raman spectroscopy. The average extent of the drug-polymer interaction in the studied amorphous samples at equivalent drug loading was similar, regardless of the preparation method. Inhomogeneities in samples prepared by melting contributed to a wider variation in drug-polymer interaction and poorer solid state stability, in terms of its crystallization tendency. Raman spectroscopy was shown to be a useful technique in classifying miscibility levels based on the hydrophobic interaction between the drug and the polymer. Different drug loadings showed varying degrees of drug-polymer interaction, and hence variable solid state stability of the solid dispersion.

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

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).

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

Correction for ‘Studies of intermolecular interactions in solid dispersions using advanced surface chemical analysis’ by M. Maniruzzaman et al., RSC Adv., 2015, 5, 74212–74219.

Effect of counterions on the interactions in solid dispersions between polyethylene glycol, griseofulvin and alkali dodecyl sulphates

Solid dispersions of polyethylene glycol (PEG) 3000 and 10% w/w griseofulvin with or without different surfactants incorporated were prepared by the melting method. The anionic surfactants lithium dodecyl sulphate (LiDS), sodium dodecyl sulphate (SDS) and potassium dodecyl sulphate (KDS) were added in equivalent amounts, ~ 2% w/w. Phase analysis was performed by X-ray powder diffraction and investigation of short-range structure by 13C-CP/MAS solid-state NMR. In all samples with surfactant added, solid solutions (PEG/MDS) 1− x griseofulvin x were formed. The properties of the solid solutions with Na + and K + ions were almost identical. The addition of LiDS created a structure of the solid solution that was more crystalline than that structure of the sodium- and potassium-containing compounds. The ion with the highest charge-to-radius ratio, Li +, formed chemical bonds that were different from those of the other ions. This was indicated by a changed influence on the hydrophilic parts of the griseofulvin molecules in the lithium compound. The melting behaviour of the solid solutions, investigated by DSC, showed a second transformation in the melt at 186–196°C, indicating a two-phase region in the liquid phase. For the lithium-containing compounds the transformation appeared at lower temperature than for the sodium- and potassium-containing compounds.

Structures formed by interactions in solid dispersions of the system polyethylene glycol-griseofulvin with charged and non charged surfactants added

Solid dispersions of polyethylene glycol (PEG) 3000 and 10% w/w griseofulvin with incorporation of different types of surfactants were prepared by the melting method. The anionic surfactant sodium dodecyl sulphate (SDS), the cationic surfactant dodecyltrimethylammonium bromide (DTAB) and the nonionic surfactant polyoxyethylene dodecyl ether (Brij) were added in equivalent amounts. Phase analysis was made by X-ray powder diffraction and investigation of the short-range structure by 13C-CP/MAS solid-state NMR. The addition of the different types of surfactants influences the structure of the dispersions in a varying manner. The anionic surfactant SDS forms a solid solution, the nonionic Brij does not influence the particulate dispersion and the cationic DTAB creates a dispersion, that only to a certain extent is a solid solution. The extent of interaction between polymer and surfactant aggregates (micelles) seems to be crucial for the formation of solid solutions of griseofulvin in the polymer phase. The charged surfactants can interact with the polymer forming aggregates, while the nonionic ones show no interaction. When a solid solution is formed, the hydrophilic parts of the griseofulvin molecule are significantly influenced. The surfactant aggregates bind griseofulvin in a molecular form at the surface or, more probably, in the interior of the aggregate.