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Many newly developed active pharmaceutical ingredients (APIs) have very low solubility in aqueous media. The preparation of solid dispersions (SDs) is one way of avoiding this problem. However, compound wettability and thus solubility are influenced by surface energy. In this study, we used inverse gas chromatography (IGC) to evaluate the surface energies of prepared SDs, and compared them with those obtained for physical mixtures (PMs). SDs containing different weight ratios of crystalline acetaminophen and one of three polymers (Kollidon ® 12 PF, Kollidon ® VA 64 or Soluplus ® ) were prepared by the melt-quenching of corresponding PMs. In all cases, as the polymer content increased, the surface energy decreased significantly. For the SDs and PMs containing Soluplus ® , this decrease in surface energy showed the same non-linear trend. In the cases of Kollidon ® 12 PF and Kollidon ® VA 64, the trend was linear, with the SDs showing a steeper decrease in surface energy than the corresponding PMs. Typically, such decreases are ascribed to the dissolution of the crystalline structure of an API. Our results suggest that in the case of the Kollidons, the steeper decrease is caused by another mechanism, namely, strong API-Kollidon interaction leading to the less wettable surface of SDs. [ABSTRACT FROM AUTHOR]

• Mixing/co-milling with chitosan increased dissolution rate of meloxicam greatly. • The observed effect was facilitated by meloxicam-chitosan interactive mixtures. • Specific surface area and total amount of the mixture were controlling parameters. • Work of adhesion/cohesion ratio of 0.9 indicated stability of interactive mixtures. • No marked drug amorphization or other crystalline structure changes were detected. To enhance dissolution rate of meloxicam (MX), a poorly soluble model drug, a natural polysaccharide excipient chitosan (CH) is employed in this work as a carrier to prepare binary interactive mixtures by either mixing or co-milling techniques. The MX-CH mixtures of three different drug loads were characterized for morphological, granulometric, and thermal properties as well as drug crystallinity. The relative dissolution rate of MX was determined in phosphate buffer of pH 6.8 using the USP-4 apparatus; a significant increase in MX dissolution rate was observed for both mixed and co-milled mixtures comparing to the raw drug. Higher dissolution rate of MX was evidently connected to surface activation by mixing or milling, which was pronounced by the higher specific surface energy as detected by inverse gas chromatography. In addition to the particle size reduction, the carrier effect of the CH was confirmed for co-milling by linear regression between the MX maximum relative dissolution rate and the total surface area of the mixture (R2 = 0.863). No MX amorphization or crystalline structure change were detected. The work of adhesion/cohesion ratio of 0.9 supports the existence of preferential adherence of MX to the coarse particles of CH to form stable interactive mixtures. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Surface energy is extensively adopted to predict the surface properties of materials nowadays. Our study was aimed at utilizing the surface free energy measured by inverse gas chromatography to determine inter-particle interactions and to describe the overall behaviour of mixtures. The model drugs of different solubility (tadalafil, levocetirizine dihydrochloride, vardenafil hydrochloride, and amlodipine besylate) and two grades of polyvinylpyrrolidone (Kollidon® 12 PF, Kollidon® VA 64) were mixed in various ratios. Investigated components were characterized using inverse gas chromatography, particle size distribution and specific surface area. We also determined the work of adhesion and cohesion between the components in the binary mixtures. Due to the formation of levocetirizine agglomerates, the effect of mixing time on both components of the surface free energy was also studied for the binary mixture with Kollidon® VA 64. The results based on the energy analysis, especially positive or negative excess surface energies in theoretical and real binary mixtures, indicate that we can predict whether the components can form the desired ordered (interactive) mixture. For this reason, we have proposed, to the best of our knowledge, different approach to predict the interactions between components and their behaviour in the binary mixtures using inverse gas chromatography in terms of the energy balance based only on the surface parameters (surface free energy, dispersive and specific surface energy). Therefore, the approach of energy balance is an innovative and comparatively simple tool for analysis and identification of interactions between components in particulate systems, which can also predict the quality of the mixing. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

[Display omitted] The aim of this study was to investigate the molecular structures of tadalafil solid dispersions prepared by different techniques and further to relate them to surface free energy information indicating the final amorphousness of the product. Thus, we tried to complement the existing knowledge of solid dispersion formation. Poorly water-soluble tadalafil was combined with different polymers, i.e. Kollidon® 12 PF, Kollidon® VA 64 and Soluplus®, to form model systems. To assess the extent of drug-polymer miscibility, we studied model solid dispersion surface energy using inverse gas chromatography and phase micro-structure using confocal Raman microscopy. The selection of the preparation method was found to play a crucial role in the molecular arrangement of the incorporated drug and the polymer in resulting solid dispersion. Our results showed that a lower surface free energy indicated the formation of a more homogeneous solid dispersion. Conversely, a higher surface free energy corresponded to the heterogeneous systems containing tadalafil amorphous clusters that were captured by Raman mapping. Thus, we successfully introduced a novel evaluation approach of the drug molecular arrangement in solid dispersions that is especially useful for examining the miscibility of the components when the conventional characterizing techniques are inconclusive or yield variable results. [ABSTRACT FROM AUTHOR]