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Stability of high indomethacin (IMC) content formulations based on ordered mesoporous silica MCM-41 and SBA-15 materials was studied before and after a 3 month storage in stressed conditions (30°C/56% RH). Overall, the physical stability of the samples was found satisfactory after the storage. However, some issues with the chemical stability were noted, especially with the MCM-41 based samples. The stability issues were evident from the decreased HPLC loading degrees of the drug after stressing as well as from the observed extra peaks in the HPLC chromatograms of the drug in the stressed samples. Drug release from the mesoporous formulations before stressing was rapid at pH 1.2 in comparison to bulk crystalline IMC. The release profiles also remained similar after stressing. Even faster and close to complete IMC release was achieved when the pH was raised from 1.2 to 6.8. To our knowledge, this is the first report of chemical stability issues of drugs in mesoporous silica drug formulations. The present results encourage further study of the factors affecting the chemical stability of drugs in mesoporous silica MCM-41 and SBA-15 formulations in order to realize their potential in oral drug delivery., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In this paper, the thermodynamics of the anhydrate/dihydrate carbamazepine (CBZA/CBZH) in ethanol-water mixtures was studied by measuring the solubility of anhydrate and dihydrate carbamazepine at 0-60 degrees C. Both stable form solubility and metastable form solubility were measured, the latter with the assistance of Raman immersion probe. The thermodynamic properties of the anhydrate/dihydrate system, such as the relative stability, and enthalpy and entropy of dissolution, were estimated by plotting the measured solubility data according to the van't Hoff equation. The anhydrate/dihydrate carbamazepine showed an enantiotropic relationship in the studied mixtures and temperature ranges. It was shown that at a certain temperature, there was an equilibrium water activity value at which the anhydrate and dihydrate carbamazepine were in equilibrium. This equilibrium water activity value depends significantly on the temperature. The lower the temperature, the smaller is the water activity value needed to attain equilibrium between anhydrate and dihydrate. The obtained results are useful in determining crystallization parameters to achieve a desired anhydrate or hydrate phase. The approach can be applied to other anhydrate and hydrate systems.

Sonocrystallization has proved to be an efficient tool to influence the external appearance and structure of a crystalline product obtained by various crystallization methods. The present work focuses on high intensity sonocrystallization of glycine by varying amplitude of ultrasound with an ultrasound frequency of 20kHz at two temperature ranges 40-50 and 20-30 degrees C in a jacketed 250-ml cooling crystallizer equipped with a stirrer. The polymorph composition of the obtained crystals was analyzed with a temperature variable X-ray powder diffractometer (XRPD). XRPD results showed that, besides the operating temperature, the glycine polymorphism was affected also by insonation. This was especially the case at the lower temperature range. Furthermore, based on the heat balance within the crystallizer, an increase in required cooling capacity was presented as a function of increasing ultrasound power. This study also showed, the higher the ultrasound amplitude the smaller the crystals obtained.