Revision of Viable Environmental Monitoring in a Development Pilot Plant Based on Quality Risk Assessment: A Case Study.

In this case study, the principles of quality risk management were applied to review sampling points and monitoring frequencies in the hormonal tableting unit of a formulation development pilot plant. In the cleanroom area, premises of different functions are located. Therefore a general method was established for risk evaluation based on the Hazard Analysis and Critical Control Points (HACCP) method to evaluate these premises (i.e., production area itself and ancillary clean areas) from the point of view of microbial load and state in order to observe whether the existing monitoring program met the emerged advanced monitoring practice.LAY ABSTRACT: In pharmaceutical production, cleanrooms are needed for the manufacturing of final dosage forms of drugs-intended for human or veterinary use-in order to protect the patient's weakened body from further infections. Cleanrooms are premises with a controlled level of contamination that is specified by the number of particles per cubic meter at a specified particle size or number of microorganisms (i.e. microbial count) per surface area. To ensure a low microbial count over time, microorganisms are detected and counted by environmental monitoring methods regularly. It is reasonable to find the easily infected places by risk analysis to make sure the obtained results really represent the state of the whole room. This paper presents a risk analysis method for the optimization of environmental monitoring and verification of the suitability of the method.

Vibrational spectroscopic study of sodium-1,2,4-triazole, an important intermediate compound in the synthesis of several active substances.

The molecular properties, geometric parameters, atomic charges, and vibrational spectra of sodium 1,2,4-triazolate were investigated with both experimentally and quantum chemical modeling. During the quantum chemical calculations the possible tautomery and the aqueous environment were considered since the compound is hygroscopic. The polar environment was modeled as an aqueous solvent, and by adding water molecules as structural water. The two kinds of effects were also applied together.

Transportation behavior of alkali ions through a cell membrane ion channel. A quantum chemical description of a simplified isolated model.

Quantum chemical model calculations were carried out for modeling the ion transport through an isolated ion channel of a cell membrane. An isolated part of a natural ion channel was modeled. The model channel was a calixarene derivative, hydrated sodium and potassium ions were the models of the transported ion. The electrostatic potential of the channel and the energy of the channel-ion system were calculated as a function of the alkali ion position. Both attractive and repulsive ion-channel interactions were found. The calculations - namely the dependence of the system energy and the atomic charges of the water molecules with respect to the position of the alkali ion in the channel - revealed the molecular-structural background of the potassium selectivity of this artificial ion channel. It was concluded that the studied ion channel mimics real biological ion channel quite well.

Increased importance of the documented development stage in process validation.

Current trends in pharmaceutical quality assurance moved when the Federal Drug Administration (FDA) of the USA published its new guideline on process validation in 2011. This guidance introduced the lifecycle approach of process validation. In this short communication some typical changes from the point of view of practice of API production are addressed in the light of inspection experiences. Some details are compared with the European regulations.

Methanol in its own gravy. A PCM study for simulation of vibrational spectra.

For studying both hydrogen bond and dipole-dipole interactions between methanol molecules (self-association) the geometry of clusters of increasing numbers of methanol molecules (n = 1,2,3) were optimized and also their vibrational frequencies were calculated with quantum chemical methods. Beside these B3LYP/6-311G** calculations, PCM calculations were also done for all systems with PCM at the same quantum chemical method and basis set, for considering the effect of the liquid continuum on the cluster properties. Comparing the results, the measured and calculated infrared spectra are in good accordance.

Formyl- and acetylindols: vibrational spectroscopy of an expectably pharmacologically active compound family.

In the present paper, indole and its seven derivatives were compared, namely 3-formylindole, 1-methyl-3-formylindole, 1-ethyl-3-formylindole, 3-acetylindole, 1-methyl-3-acetylindole, 1-ethyl-3-acetylindole and 1,3-diacetylindole. The substitution of indole in position 3 with aldehydes and with alkyl groups cause only minor changes in the molecular geometry, however, substantially larger alterations are found in the charge distribution and in the vibrational force constants. The appearance of the aldehyde groups increased the degree of association as it was observable on the shape of infrared NH stretching band and its shifts. The alkyl substitution shifts the aldehyde carbonyl stretch band frequencies to somewhat higher values. The effect of the second acetyl group in position 1 is not comparable with those of the 1-alkyl groups. The latter effect is observable in the molecular geometry, however, it is more pronounced in the changes of the net charge distribution, the vibrational force constants and the infrared spectra.

Vibrational spectroscopy of resveratrol.

In this article the authors deal with the experimental and theoretical interpretation of the vibrational spectra of trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene) of diverse beneficial biological activity. Infrared and Raman spectra of the compound were recorded; density functional calculations were carried out resulting in the optimized geometry and several properties of the molecule. Based on the calculated force constants, a normal coordinate analysis yielded the character of the vibrational modes and the assignment of the measured spectral bands.

Complex formation between aliphatic amines and chromogenic calix[4]arene derivatives studied by FT-IR spectroscopy.

Complex formation of two calix[4]arene derivatives - containing two ethoxycarbonylmethoxy groups or a bridge including two carboxamide moieties in the coordination sphere - with aliphatic amines (n-octylamine, OA and triethylamine, TEA) were the subject of FT-IR studies. Two nitrophenyl type auxochromic moieties were also present in both of the ligands. Solvent effects were studied in chloroform, diiodomethane and dichloromethane. Presumably, in these reactions, the reactants undergo phenol-amine type interactions and, simultaneously, coordinative interaction takes place between the carbonyl group of the ligand and the protonated form of the aliphatic amine. Complex formation of calixarene 1a with n-octylamine was complete resulting in drastic changes in the FT-IR spectra. Moreover, the possibility of the formation of a new compound by the reaction between the ester type functionalities and octylamine was precluded. The expected ligand was synthesized and its spectra were compared with those of calixarene 1a. In most of the cases of calixarene 1b, the amide moiety of the carboxamide bridge does not participate in the complex formation with the exception of complexes formed in diiodomethane solution and of the 1b-TEA complex observed in dichloromethane.

Selective complex formation of some chromogenic calix[4]arene derivatives detected by Fourier transform infrared spectroscopy 2. Solid experiments.

Two chromogenic calix[4]arene derivatives having identical coordination sphere (consisting of ester groups) but different chromogenic units (pyridinium type and dinitro-phenyl type) were the subject of structural studies with sodium(I) and thallium(I) ions in solid state, both as bulk and surface complexes. Their diffuse reflectance infrared Fourier transform (DRIFTS) spectra were recorded and the characteristic changes of the vibrational spectra due to complex formation were analysed based on curve fitting.

Selective complex formation of some chromogenic calix[4]arene derivatives detected by Fourier transform infrared spectroscopy 1. Solution experiments.

A calix[4]arene derivative containing ethoxycarbonylmethoxy groups in the coordination sphere and an iminopyridinium indicator group was studied by FT-IR spectroscopy in acetonitrile solution. The characteristic changes of v(C=O) stretching vibration offered an opportunity for the improvement on selectivity of the ion recognition process of this ligand. The shift of the carbonyl stretching vibration band depended on complex formation as well as on the equilibrium constants of complex formation. In the case of sodium complex, a well-defined isobestic point was detected in the v(C=O) region while altering the sodium concentration. The affinity of thallium(III) to form complex with calixarene 1 was found comparable with those of lithium, sodium or calcium. The complex was found to be an M2L type supramolecule, whereas one molecule of triethylamine was necessary for the formation of each complex.