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Meloxicam (MLX) is a poorly soluble drug exhibiting strong hydrophobicity. This combination of properties makes dissolution enhancement by particle size reduction ineffective; therefore, combined formulation approaches are required. Various approaches were investigated in this study, including milling, solid dispersions, and self-emulsified lipid formulations. Whereas milling studies of MLX and its co-milling with various polymers have been reported in recent literature, this study is focused on investigating the dissolution kinetics of particulate formulations obtained by co-milling MLX with sodium lauryl sulfate (SLS) in a planetary ball mill with 5–25 wt.% SLS content. The effects of milling time and milling ball size were also investigated. No significant reduction in drug crystallinity was observed under the investigated milling conditions according to XRD data. For the dissolution study, we used an open-loop USP4 dissolution apparatus, and recorded dissolution profiles were fitted according to the Weibull model. The Weibull parameters and a novel criterion—surface utilization factor—were used to evaluate and discuss the drug release from the perspective of drug particle surface changes throughout the dissolution process. The most effective co-milling results were achieved using smaller balls (2 mm), with a co-milling time of up to 15 min SLS content of up to 15 wt.% to increase the dissolution rate by approximately 100 times relative to the physical mixture reference. The results suggest that for hydrophobic drugs, particle performance during dissolution is very sensitive to surface properties and not only to particle size. Co-milling with SLS prepares the surface for faster drug release than that achieved with direct mixing. [ABSTRACT FROM AUTHOR]

The aims of this study were to investigate how the release of tadalafil is influenced by two grades of polyvinylpyrrolidone (Kollidon® 12 PF and Kollidon® VA 64) and various methods of preparing solid dispersions (solvent evaporation, spray drying and hot-melt extrusion). Tadalafil is poorly water-soluble and its high melting point makes it very sensitive to the solid dispersion preparation method. Therefore, the objectives were to make a comparative evaluation among different solid dispersions and to assess the effect of the physicochemical nature of solid dispersions on the drug release profile with respect to the erosion-diffusion mechanism. The solid dispersions were evaluated for dissolution profiles, XRD, SEM, FT-IR, DSC, and solubility or stability studies. It was found that tadalafil release was influenced by polymer molecular weight. Therefore, solid dispersions containing Kollidon® 12 PF showed a faster dissolution rate compared to Kollidon® VA 64. Tadalafil was released from solid dispersions containing Kollidon® 12 PF because of the combination of erosion and diffusion mechanisms. The diffusion mechanisms were predominant in the initial phase of the experiment and the slow erosion was dissolution-controlling at the second stage of the dissolution. On the contrary, the tadalafil release rate from solid dispersions containing Kollidon® VA 64 was controlled solely by the erosion mechanism. [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]

[Display omitted] • Co-milling of drugs having different glass forming ability with suitable co-formers. • Characterization of dissolution properties of physical and co-milled mixtures. • Solid state characterization of prepared mixtures. • The proper choice of excipient is the key to maximizing the dissolution rates. • The glass forming ability of the drug affects the properties of composite particles. Co-milling of a drug with a co-former is an efficient technique to improve the solubility of drugs. Besides the particle size reduction, the co-milling process induces a structural disorder and the creation of amorphous regions. The extent of drug solubility enhancement is dependent on the proper choice of co-milling co-former. The aim of this work was to compare the effects of different co-formers (meglumine and polyvinylpyrrolidone) on the dissolution rates of glass forming (indomethacin) and non-glass forming (mefenamic acid) model drugs. A positive impact of the co-milling on the dissolution behavior was observed in all co-milled mixtures, even if no substantial amorphization was observed. While meglumine exhibited pronounced effects on the dissolution rate of both drugs, the slightest enhancement was observed in mixtures with polyvinylpyrrolidone. The evaluation of specific release rate revealed the surface activation of drug particle is responsible for improving the dissolution rate of both drug types, but for the glass former, this surface activation could be persistent while maintaining a high dissolution rate even until a high fraction of drug is released. Our results, therefore, indicate that adequate co-former choice and consideration of drug glass forming ability are important for a successful co-milling approach to poorly water-soluble drugs. [ABSTRACT FROM AUTHOR]