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.

• Klíčová slova
• co-milling, dissolution kinetics, dissolution rate, enhanced dissolution, meloxicam, sodium lauryl sulfate, surface modification,
• Publikační typ
• časopisecké články MeSH

The aim of this study is to present the possibility of using of co-processed dry binders for formulation of matrix tablets with drug controlled release. Hydrophilic matrix tablets with tramadol hydrochloride, hypromellose and different co-processed dry binders were prepared by direct compression method. Hypromelloses Methocel™ K4M Premium CR or Methocel™ K100M Premium CR were used as controlled release agents and Prosolv® SMCC 90 or Disintequik™ MCC 25 were used as co-processed dry binders. Homogeneity of the tablets was evaluated using scanning electron microscopy and energy dispersive X-ray microanalysis. The release of tramadol hydrochloride from prepared formulations was studied by dissolution test method. The dissolution profiles obtained were evaluated by non-linear regression analysis, release rate constants and other kinetic parameters were determined. It was found that matrix tablets based on Prosolv® SMCC 90 and Methocel™ Premium CR cannot control the tramadol release effectively for >12h and tablets containing Disintequik™ MCC 25 and Methocel™ Premium CR >8h.

• Klíčová slova
• Co-processed dry binders, Dissolution kinetics, Hypromellose, Matrix tablets, Tramadol hydrochloride,
• MeSH
• deriváty hypromelózy chemie   farmakokinetika   MeSH
• farmaceutická chemie metody   MeSH
• hydrofobní a hydrofilní interakce * MeSH
• rozpustnost MeSH
• tablety MeSH
• tramadol chemie   farmakokinetika   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• deriváty hypromelózy MeSH
• tablety MeSH
• tramadol MeSH

Biorelevant dissolution instruments represent an important tool for pharmaceutical research and development. These instruments are designed to simulate the dissolution of drug formulations in conditions most closely mimicking the gastrointestinal tract. In this work, we focused on the optimization of dissolution compartments/vessels for an updated version of the biorelevant dissolution apparatus-Golem v2. We designed eight compartments of uniform size but different inner geometry. The dissolution performance of the compartments was tested using immediate release caffeine tablets and evaluated by standard statistical methods and principal component analysis. Based on two phases of dissolution testing (using 250 and 100 mL of dissolution medium), we selected two compartment types yielding the highest measurement reproducibility. We also confirmed a statistically ssignificant effect of agitation rate and dissolution volume on the extent of drug dissolved and measurement reproducibility.

• Klíčová slova
• Golem, biorelevant, caffeine, dissolution, multivariate data analysis,
• MeSH
• biologické modely * MeSH
• design vybavení MeSH
• farmaceutická chemie * MeSH
• farmakokinetika * MeSH
• gastrointestinální absorpce MeSH
• gastrointestinální trakt metabolismus   MeSH
• multivariační analýza MeSH
• počítačová simulace MeSH
• rozpustnost * MeSH
• Publikační typ
• časopisecké články MeSH

The effect of process scale-up from 4 to 400-L high-shear granulator on the release kinetics of the active ingredient from pharmaceutical granules has been investigated. The dissolution and disintegration rates of the granules were measured simultaneously by the combination of UV/vis spectroscopy and static light scattering. The granule batches were found to consist of sub-populations with qualitatively different dissolution behavior: "weaker" granules that disintegrated during dissolution, and "stronger" granules that retained their size and from which the active ingredient was gradually leached. The existence of these sub-populations was attributed to non-uniform distribution of normal and shear forces that prevail in granulators of different size. This hypothesis was confirmed by preparing granules at increasing values of the Froude number at the 4-L scale, and observing a transition from the break-up dissolution mode to the leaching dissolution mode with increasing granule densification. The simultaneous observation of solute concentration and particle size distribution during granules dissolution proved to be a useful tool for the understanding of dissolution mechanisms and for identifying non-uniformities of process conditions that can occur during scale-up.

• Klíčová slova
• High-shear granulation, Laser diffraction, Particle size distribution, Release curve, Scale-up,
• MeSH
• farmaceutická chemie * MeSH
• kinetika MeSH
• mikroskopie elektronová rastrovací MeSH
• rentgenová mikrotomografie MeSH
• rozpustnost * MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• Weibull dissolution model, Wood’s apparatus, dissolution rate, intrinsic dissolution rate, solid dispersion, tadalafil,
• Publikační typ
• časopisecké články MeSH

The sorption of poorly aqueous soluble active pharmaceutical ingredients (API) to mesoporous silica carriers is an increasingly common formulation strategy for dissolution rate enhancement for this challenging group of substances. However, the success of this approach for a particular API depends on an array of factors including the properties of the porous carrier, the loading method, or the attempted mass fraction of the API. At present, there is no established methodology for the rational selection of these parameters. In the present work, we report a systematic comparison of four well-characterised silica carriers and seven APIs loaded by the same solvent evaporation method. In each case, we find the maximum amorphization capacity by x-ray powder diffraction analysis and measure the in vitro drug release kinetics. For a selected case, we also demonstrate the potential for bioavailability enhancement by a permeation essay.

• Klíčová slova
• Amorphization, Dissolution kinetics, Evaporation loading, Mesoporous silica particles,
• MeSH
• kinetika MeSH
• nosiče léků * MeSH
• oxid křemičitý * MeSH
• poréznost MeSH
• rozpouštědla MeSH
• rozpustnost MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nosiče léků * MeSH
• oxid křemičitý * MeSH
• rozpouštědla MeSH

On modelling the kinetics of dissolution, two variants of Weibull equation in a two-parameter or tree-parameter form are used, the estimations of their parameters not being quite comparable. The introductory part of the paper sums up four variants of the equation and chracterized their relationship to granulometric Rosin-Rammler-Sperling equation. The kinetics of liberation of pilocarpinium chloride from lyophilized lamellae with graded amounts of hydroxypropylmethylcellulose is expressed by the above-mentioned equations and their parameters are compared. The conclusions generally discusses the usability of equations and their correct interperetation in modelling dissolution of active ingrediens from dosage forms.

• MeSH
• chemické jevy MeSH
• deriváty hypromelózy MeSH
• fyzikální chemie MeSH
• kinetika MeSH
• methylcelulosa * analogy a deriváty   MeSH
• pilokarpin * MeSH
• rozpustnost * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• deriváty hypromelózy MeSH
• methylcelulosa * MeSH
• pilokarpin * MeSH

Development of new pharmaceutical compounds and dosage forms often requires in vitro dissolution testing with the closest similarity to the human gastrointestinal (GI) tract. To create such conditions, one needs a suitable dissolution apparatus and the appropriate data on the human GI physiology. This review discusses technological approaches applicable in biorelevant dissolutions as well as the physiology of stomach and small intestine in both fasted and fed state, that is, volumes of contents, transit times for water/food and various solid oral dosage forms, pH, osmolality, surface tension, buffer capacity, and concentrations of bile salts, phospholipids, enzymes, and Ca(2+) ions. The information is aimed to provide clear suggestions on how these conditions should be set in a dynamic biorelevant dissolution test.

• Klíčová slova
• bioavailability, bioequivalence, biorelevant dissolution, dissolution, dynamic dissolution, gastrointestinal physiology, gastrointestinal transit, in vitro models,
• MeSH
• farmaceutická chemie metody   MeSH
• farmakokinetika * MeSH
• gastrointestinální trakt fyziologie   MeSH
• léčivé přípravky chemie   MeSH
• lidé MeSH
• rozpustnost MeSH
• tenké střevo fyziologie   MeSH
• žaludek fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• léčivé přípravky MeSH

The aim of this study was to improve rivaroxaban water-solubility by cocrystal preparation and to understand this process. The screening with water-soluble coformers was performed via both mechanochemical and solution-mediated techniques. Two cocrystals of rivaroxaban with malonic acid and oxalic acid were prepared, and the structure of the cocrystal with oxalic acid was solved. Both cocrystals exhibit improved dissolution properties. The mechanism of the supersaturation maintenance was studied by in-situ Raman spectroscopy. The transformation into rivaroxaban dihydrate was identified as the critical step in the improved dissolution properties of both cocrystals. Moreover, the transformation kinetics and solubilization effects of the coformers were identified as responsible for the differences in the dissolution behavior of the cocrystals. In-vivo experiments proved that the use of cocrystal instead of form I of free API helped to increase the bioavailability ofrivaroxaban.

• Klíčová slova
• Cocrystal, Dissolution, In-vivo studies, Rivaroxaban, Solid form transformation, Solubilization,
• MeSH
• difrakce rentgenového záření MeSH
• krystalizace MeSH
• kyselina oxalová MeSH
• rivaroxaban * MeSH
• rozpustnost MeSH
• voda * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyselina oxalová MeSH
• rivaroxaban * MeSH
• voda * MeSH

Powder samples prepared from gasoline (Pt, Pd, Rh, new GN/old GO) and diesel (Pt, new DN/old DO) catalysts and recycled catalyst NIST 2556 were tested using kinetic leaching experiments following 1, 12, 24, 48, 168, 360, 720 and 1440-h interactions with solutions of 20mM citric acid (CA), 20 mM Na(2)P(4)O(7) (NaPyr), 1 g L(-1) NaCl (NaCl), a fulvic acid solution (FA-DOC 50 mg L(-1)) and 20 mM CA at pH 3, 4, 5, 6, 7, 8 and 9. The mobilisation of platinum group elements (PGEs) was fastest in solutions of CA and NaPyr. In the other interactions (NaCl, FA), the release of PGEs was probably followed by immobilisation processes, and the interactions were not found to correspond to the simple release of PGEs into solution. Because of their low concentrations, the individual complexing agents did not have any effect on the speciation of Pd and Pt in the extracts; both metals are present in solution as the complexes Me(OH)(2), Me(OH)(+). Immobilisation can take place through the adsorption of the positively charged hydroxyl complexes or flocculation of fulvic acid, complexing the PGEs on the surface of the extracted catalysts. The calculated normalised bulk released NRi values are similar to the reaction rate highest in the solutions of CA and NaPyr.

• MeSH
• automobily MeSH
• katalýza MeSH
• kinetika MeSH
• mikroskopie elektronová rastrovací MeSH
• palladium chemie   MeSH
• platina chemie   MeSH
• rozpustnost MeSH
• výfukové emise vozidel * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• palladium MeSH
• platina MeSH
• výfukové emise vozidel * MeSH