New biologically active sulfonamides as potential drugs for Alzheimer's disease.

A family of new compounds with sulfonamide and amide functional groups as potential Alzheimer's disease drugs were prepared by multistep synthesis. Thermal stability measurements recorded the initial decomposition in the range of 200-220°C, close above the melting point. The final compounds were tested for their ability to inhibit acetylcholinesterase and butyrylcholinesterase, and the in vitro dissolution behavior of selected compounds was studied through both lipophilic and hydrophilic matrix tablets.

Thermal stability of amorphous nimesulide: from glass formation to crystal growth and thermal degradation.

Thermally induced physico-chemical transformations in amorphous nimesulide were studied by means of differential scanning calorimetry (DSC), thermogravimetry, and Raman microscopy. The equilibrium glass transition temperature was found to be = 10-15 °C, and the relaxation motions were found to be temperature-dependent. Crystal growth from the amorphous phase was found to be crucially dependent on the presence of mechanical defects that serve as centers for heterogeneous nucleation.

Thermal degradation of Affinisol HPMC: Optimum Processing Temperatures for Hot Melt Extrusion and 3D Printing.

Purpose: Affinisol HPMC HME is a new popular form of hypromellose specifically designed for the hot melt extrusion and 3D printing of pharmaceutical products. However, reports of its thermal stability include only data obtained under inert N atmosphere, which is not consistent with the common pharmaceutical practice. Therefore, detailed investigation of its real-life thermal stability in air is paramount for identification of potential risks and limitations during its high-temperature processing.

Indomethacin: Effect of Diffusionless Crystal Growth on Thermal Stability during Long-Term Storage.

Differential scanning calorimetry and Raman spectroscopy were used to study the nonisothermal and isothermal crystallization behavior of amorphous indomethacin powders (with particle sizes ranging from 50 to 1000 µm) and their dependence on long-term storage conditions, either 0-100 days stored freely at laboratory ambient temperatures and humidity or placed in a desiccator at 10 °C. Whereas the γ-form polymorph always dominated, the accelerated formation of the α-form was observed in situations of heightened mobility (higher temperature and heating rate), increased amounts of mechanically induced defects, and prolonged free-surface nucleation. A complex crystallization behavior with two separated crystal growth modes (originating from either the mechanical defects or the free surface) was identified both isothermally and nonisothermally.

Indomethacin: The Interplay between Structural Relaxation, Viscous Flow and Crystal Growth.

Non-isothermal differential scanning calorimetry (DSC) was used to study the influences of particle size (d) and heating rate (q) on the structural relaxation, crystal growth and decomposition kinetics of amorphous indomethacin. The structural relaxation and decomposition processes exhibited d-independent kinetics, with the q dependences based on the apparent activation energies of 342 and 106 kJ·mol, respectively. The DSC-measured crystal growth kinetics played a dominant role in the nucleation throughout the total macroscopic amorphous-to-crystalline transformation: the change from the zero-order to the autocatalytic mechanism with increasing q, the significant alteration of kinetics, with the storage below the glass transition temperature, and the accelerated crystallization due to mechanically induced defects.

Matrix Tablets Based on Chitosan-Carrageenan Polyelectrolyte Complex: Unique Matrices for Drug Targeting in the Intestine.

The present study focused on the more detailed characterization of chitosan-carrageenan-based matrix tablets with respect to their potential utilization for drug targeting in the intestine. The study systematically dealt with the particular stages of the dissolution process, as well as with different views of the physico-chemical processes involved in these stages. The initial swelling of the tablets in the acidic medium based on the combined microscopy-calorimetry point of view, the pH-induced differences in the erosion and swelling of the tested tablets, and the morphological characterization of the tablets are discussed.

3D-Printed Coating of Extended-Release Matrix Tablets: Effective Tool for Prevention of Alcohol-Induced Dose Dumping Effect.

Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect.

A Critical Overview of FDA and EMA Statistical Methods to Compare In Vitro Drug Dissolution Profiles of Pharmaceutical Products.

A drug dissolution profile is one of the most critical dosage form characteristics with immediate and controlled drug release. Comparing the dissolution profiles of different pharmaceutical products plays a key role before starting the bioequivalence or stability studies. General recommendations for dissolution profile comparison are mentioned by the EMA and FDA guidelines.

Influence of particle size and manufacturing conditions on the recrystallization of amorphous Enzalutamide.

Non-isothermal differential scanning calorimetry was used to study the influences of particle size and mechanically induced defects on the recrystallization kinetics of amorphous Enzalutamide. Enzalutamide prepared by hot melt extrusion and spray-drying was used as a model material. The recrystallization rate was primarily accelerated by the presence of the processing-damaged surface of the powder particles.

The effect of alcohol on ionizing and non-ionizing drug release from hydrophilic, lipophilic and dual matrix tablets.

The aim of this work was to investigate and quantitatively evaluate the effect of presence of alcohol on release of ionizing and non-ionizing drug from hydrophilic, lipophilic and hydrophilic-lipophilic matrix tablets. The Food and Drug Administration (FDA) recommends dissolution testing of extended release formulations in ethanolic media up to 40% because of possible alcohol-induced dose dumping effect. This study is focused on comparison of the dissolution behavior of matrix tablets (based on hypromellose and/or glyceryl behenate as retarding agent) of the same composition containing different type of drug - ionizing tramadol hydrochloride (TH) and non-ionizing pentoxifylline (PTX).

Comparative evaluation of the use of dry binders in a physical mixture or as a coprocessed dry binder in matrix tablets with extended drug release.

This paper evaluates and compares the properties of directly compressible tabletting materials and matrix tablets containing a combination of α-lactose monohydrate and microcrystalline cellulose in the 3:1 ratio in a physical mixture and in a coprocessed dry binder. Tested parameters include flow properties, compressibility, compactibility and the rate of drug release from tablets. Compressibility is evaluated by means of the energy profile of the compression process.

Formulation and dissolution kinetics study of hydrophilic matrix tablets with tramadol hydrochloride and different co-processed dry binders.

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.

STUDY OF DUAL MATRIX TABLETS CONTAINING HYPROMELLOSE OF DIFFERENT VISCOSITY DEGREE AND GLYCERYL DIBEHENATE.

Studies are described on the compressibility of directly compressible tableting materials containing two viscosity types of hypromellose in two concentrations and tableting materials containing additional glyceryl dibehenate, also in two concentrations. Compressibility is evaluated by means of the energy profile of the compression process and determination of tensile strength of tablets. Dissolution test examines the rate of release of the active ingredient from matrix tablets, which is subsequently evaluated mathematically.

Compressibility of tableting materials and properties of tablets with glyceryl behenate.

The paper studies the compressibility of directly compressible tableting materials with dry binders, spray-dried lactose and microcrystalline cellulose, and glyceryl dibehenate at various concentrations. Compressibility was evaluated by means of the energy profile of compression and tensile strength of tablets. Release rate of the active ingredient, salicylic acid, from the tablets was also examined.

Inhibition of cholinesterase by dialkylcarbamates.

The pI50 index and separation coefficients of chosen 3-N,N-diethylaminophenyl-N',N'-dialkylcarbamates were determined. Index pL50 (pI50 = negative logarithm of molar concentration of inhibitor inhibiting the enzyme activity by 50%) describes the effectiveness of the inhibitor. The rate of ability of the inhibitor to pass the blood-brain barrier is usually described by the separation coefficient in a system n-octanol/water (K(ow)).

In vitro inhibition of cholinesterases by carbamates--a kinetic study.

Kinetics and mechanism of in vitro hydrolyses of acetylcholine and acetylthiocholine by carbamates were studied in a batch reactor at 25 degrees C, pH 8, and ionic strength of 0.11 M. Every hydrolysis was monitored by 3-4 independent methods.

New findings about Ellman's method to determine cholinesterase activity.

The original Ellman's spectrophotometrical method for cholinesterase activity determination uses 5,5'-dithiobis-2-nitrobenzoic acid (DTNB, Ellman's reagent) as a chromogen and records the level of cholinesterase activity as an increase of absorbance at 412 nm. Although this procedure usually poses no problem, exceptions arise when the concentration of DTNB is far higher than the concentration of acetylthiocholine (ATCH). It was found that the ratio of concentrations of DTNB/ATCH is an important parameter for the ATCH hydrolysis course: high excess of DTNB decreases the hydrolysis rate resulting in a lower measured enzyme activity.

Kinetics of 13 new cholinesterase inhibitors.

Kinetics of hydrolysis of acetylcholine and acetylthiocholine by two types of acetylcholinesterase and butyrylcholinesterase inhibited by 13 new inhibitors (5 carbamates and 8 carbazates--hydrazinium derivatives) was measured in vitro in a batch reactor at 25 degrees C, pH 8, ionic strength 0.11 M and enzyme activity 3.5 U by four nondependent analytical methods.

Kinetics of total enzymatic hydrolysis of acetylcholine and acetylthiocholine.

Kinetics and the mechanism of total in vitro hydrolyses (i.e. up to the exhaustion of substrate) of acetylcholine and acetylthiocholine by acetylcholinesterase and butyrylcholinesterase were studied in vitro in a batch reactor at 25 degrees C, pH 8 and ionic strength of 0.

Two new methods monitoring kinetics of hydrolysis of acetylcholine and acetylthiocholine.

Hydroxylamine and HPLC methods, measuring in vitro kinetics of enzymatic hydrolysis of acetylcholine or acetylthiocholine by cholinesterases, are described. The hydroxylamine method determines the dependence of substrate concentration vs. time, the HPLC method is able to measure simultaneously the time dependences of substrate and both primary products, choline or thiocholine, and acetic acid.