Molecular aggregation in aqueous media is one of the factors which largely affects the efficacy of photosensitizers in photodynamic therapy. Chlorin e6 (Ce6) in aggregated form is known to exhibit markedly reduced therapeutic effects. In the present study, aggregate to monomer conversion of Ce6 was investigated as a function of pH and polyvinylpyrrolidone (PVP) concentration by simple absorption and fluorescence spectroscopic techniques. Aggregation of Ce6 was observed in the pH range of 2 to 6 as indicated by changes in UV-vis absorption spectra, fluorescence emission spectra and relative quantum yield. Novel chemometric approach was considered for determining the relative monomerization efficiency of different grades of PVP. The chemometric analysis and binding constant study both strongly revealed that the Ce6-PVP complex was more efficiently formed with PVP of the lowest molecular weight (K17). Thermodynamic parameters, such as the heat of entropy and enthalpy, showed that complex formation was largely attributed to hydrophobic interaction between Ce6 and PVP. This was found to be consistent with the results obtained from molecular simulation study.

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Clear understanding of the relationships among crystal structure, mechanical properties, and tableting performance is of enormous importance for successful development of tablet products. This study was aimed at systematically examining such relationships using four salts of diphenhydramine (DPH), a first-generation H-receptor antagonist, i.e., hydrochloride (DPH-HCl), citrate (DPH-Cit), saccharinate (DPH-Sac), and acesulfamate (DPH-Acs). The conformation and intermolecular interactions of DPH as well as crystal packing in the four salts were considerably different. Both the energy framework and visualization of the crystal structure revealed the greatest plasticity of DPH-Acs, which was characterized by drastically different intermolecular interactions in orthogonal directions. This was consistent with its facile bending behavior and the lowest hardness. The most plastic DPH-Acs also exhibited the best tabletability, which was accompanied by greater compressibility and compactibility as well as smaller elastic recovery than the other three salts. Among the three hard brittle DPH salts, higher crystal hardness corresponded to poorer tabletability. This work demonstrates the technological feasibility of understanding or even predicting tableting performance based on crystal structures and mechanical properties.

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Wideband reflectance tympanometry was performed on twelve chinchillas ears. The complex input impedance of the middle ear, multifrequency admittance tympanograms, reflectance patterns (reflectance versus frequency), and reflectance tympanograms (reflectance versus ear-canal air pressure) were analyzed and compared to human data. The complex impedance of the chinchilla ear has a lower stiffness reactance at low frequencies, a higher mass reactance at high frequencies, and a lower resistance compared to the human. Multifrequency admittance tympanograms from chinchillas follow the same sequence of patterns as humans for low frequencies (<2 kHz). At higher frequencies tympanograms from both species are poorly organized and do not follow a consistent sequence of patterns. Reflectance patterns of chinchillas and humans are different. However, both species show high reflectance at low frequencies, regions of lower reflectance in mid-frequencies (2-6 kHz), and high reflectance at high frequencies (>8 kHz). Reflectance tympanograms for the two species show a single, centrally located minimum at low frequencies (<2 kHz) and are substantially different at higher frequencies. Results are shown for two animals that underwent eustachian tube obstruction. Reflectance patterns obtained with different ear-canal air pressures are substantially different. Reflectance results at any single ear-canal pressure (including ambient pressure) do not completely characterize the effects of middle-ear pathology.