potassium-acetate and potassium-phosphate

Oral potassium replacement is still inevitable. To reduce the irritation of the gastric and intestinal mucosa, pellet and matrix based formulations ensuring extended release of potassium chloride are used. The dissolution tests may help to understand the in vivo steps of the release of potassium chloride and the absorption of potassium.. Using dissolution tests extended to 12 hours the authors evaluated potassium chloride release characteristics of pellet and matrix tablet based formulations used for potassium replacement.. The tests were performed in line with the CPMP/EWP/QWP/1401/98 guideline at nine time points (0, 1, 2, 3, 4, 5, 7, 9 and 12 hours) in three dissolution media (0.1 M hydrochloric acid, pH 1.2; acetate buffer, pH 4.5; phosphate buffer, pH 6.8).. Similar results were found in all three dissolution media.. It is conceivable, that the release of potassium chloride begins already in the stomach (pH = 1.2) and at an average speed of gastrointestinal transit - in about 6-7 hours - 80% of the potassium chloride content of both formulations is dissolved by the time of the entrance to the large bowel. It seems likely, that in vivo in the proximal section of the gastrointestinal tract more potassium chloride is dissolved out of the matrix based formulation, than from the pellet based one. Both formulations meet the clinical requirements of the effective potassium chloride release.. Bevezetés: Az orális káliumpótlás számos betegség esetében ma is elkerülhetetlen. A gyomor-, bélnyálkahártya irritációjának csökkentése végett általában elnyújtott kálium-klorid-leadású pelletizált vagy mátrixszerkezetű gyógyszerformákat használnak. A kioldódási vizsgálatok segítséget nyújthatnak a kálium-klorid-leadás és a káliumfelszívódás in vivo történéseinek megértéséhez. Célkitűzés: A szerzők egy pellet- és egy mátrixtabletta-szerkezetű, káliumpótlásra használatos gyógyszerforma kálium-klorid-leadását vizsgálták 12 óra időtartamra kiterjesztett kioldódási vizsgálattal. Módszer: A vizsgálatot a CPMP/EWP/QWP/1401/98 irányelvnek megfelelően végezték el. A mérések kilenc időpontban (0, 1, 2, 3, 4, 5, 7, 9, 12 óra) és három kioldóközegben (0,1 M sósav, pH 1,2; acetátpuffer, pH 4,5; foszfátpuffer, pH 6,8) történtek. Eredmények: Mindhárom kioldóközegben hasonló eredményeket kaptak. Következtetések: Feltételezhető, hogy a kálium-klorid felszabadulása mindkét gyógyszerforma esetében már a gyomorban (pH = 1,2) megkezdődik, és átlagos sebességű passzázs során – 6–7 óra alatt – a vastagbélbe való belépés idejére mindkét gyógyszerformából kioldódik a kálium-klorid-tartalom 80%-a. Valószínűnek látszik, hogy in vivo a mátrixtablettából a gastrointestinalis traktus proximalis szakaszán nagyobb arányban oldódik ki a kálium-klorid, mint a pellettechnológiával készült készítményből. Mindkét gyógyszerforma teljesíti a hatékony kálium-klorid-leadás klinikai feltételeit. Orv. Hetil., 2015, 156(12), 479–482.

Topics: Administration, Oral; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Implants; Humans; Hydrogen-Ion Concentration; Phosphates; Potassium Acetate; Potassium Chloride; Potassium Compounds; Solubility; Solvents; Tablets

This study investigates the thermodynamics of the interaction of the TATA box binding protein (TBP) from Pyrococcus woesei (Pw) with an oligonucleotide containing a specific binding site. Pw is a hyperthermophilic archeal organism which exists under conditions of high salt and high temperature. A measurable protein-DNA interaction only occurs at high salt concentrations. Isothermal titration calorimetric binding studies were performed under a range of salts (potassium chloride, potassium phosphate, potassium acetate and sodium acetate) at varying concentrations (0.8 to 1.6 M). At the high salt concentrations used the observed equilibrium binding constant increases with increasing salt concentration. This is very different to the effect reported for all other protein-DNA interactions which have been studied at lower salt concentrations. Thermodynamic data suggest that the protein-DNA interaction at high salt concentration is accompanied by the removal of large numbers of water molecules from the buried hydrophobic surface area. In addition, the involvement of ions appears to influence the binding which can be explained by binding of cations in the interface between the electrostatically negative lateral lobes on the protein and the negatively charged DNA.

Topics: Amino Acid Sequence; Archaeal Proteins; DNA-Binding Proteins; Gene Expression Regulation, Archaeal; Genes, Archaeal; Molecular Sequence Data; Oligonucleotides; Osmolar Concentration; Phosphates; Potassium Acetate; Potassium Chloride; Potassium Compounds; Pyrococcus; Salts; Sequence Alignment; Sequence Homology, Amino Acid; Sodium Acetate; TATA-Box Binding Protein; Temperature; Transcription Factors

The isolated, 101-residue long C-terminal (so called F2) fragment of the beta chain from Escherichia coli tryptophan synthase was shown previously to fold into an ensemble of conformations that are condensed, to contain large amounts of highly dynamic secondary structures, and to behave as a good model of structured intermediates that form at the very early stages of protein folding. Here, solvent perturbations were used to investigate the forces that are involved in stabilizing the secondary structure (monitored by far-UV CD) and the condensation of the polypeptide chain (monitored by dynamic light scattering) in isolated F2. It was observed that neither the ionic strength, nor the pH (between 7 and 10), nor salts of the Hofmeister series affected the global secondary structure contents of F2, whereas some of these salts affected the collapse slightly. Addition of trifluoroethanol resulted in a large increase in both the amount of secondary structure and the Stokes radius of F2. Conversely, F2 became more condensed upon raising the temperature from 4 to 60 degrees C, whereas in this temperature range, the secondary structure undergoes significant melting. These observations lead to the conclusion that, in isolated F2, there is no coupling between the hydrophobic collapse and the secondary structure. This finding will be discussed in terms of early events in protein folding.

Topics: Chemical Phenomena; Chemistry, Physical; Circular Dichroism; Dimerization; Enzyme Stability; Escherichia coli; Hydrogen-Ion Concentration; Molecular Weight; Osmolar Concentration; Peptide Fragments; Phosphates; Potassium Acetate; Potassium Chloride; Potassium Compounds; Protein Folding; Protein Structure, Secondary; Trifluoroethanol; Tryptophan Synthase