An experimental mixture design was applied to a differential scanning calorimetry (DSC) study performed to evaluate naproxen
compatibility in tablet formulations consisting of four classic excipients (sorbitol, sodium carboxymethylcellulose, poly(ethylene
glycol) 20000 and Veegum) each in adequate concentration ranges accounting for the relevant values actually used in pharmaceutical
formulations. Twenty-seven different tablets were obtained from as many mixtures prepared according to the experimental design
plan and analyzed in a random order by DSC. Statistical evaluation of experimental data enabled correlation of both enthalpy
and onset temperature variations of drug melting endotherm (selected as responses indicative of the presence of drug-excipient
interactions) with the mixture composition. Variance analysis (Anova) confirmed the reliability of the postulated polynomial
model in providing adequate prediction of true system behaviour.
Authors:S. Romero, P. Bustamante, B. Escalera, M. Cirri, and P. Mura
Differential scanning calorimetry (DSC), supported by hot stage microscopy, IR spectroscopy and X-ray powder diffractometry,
was used to investigate the characteristics of the solid phases of mefenamic, niflumic, and flufenamic acids and of paracetamol,
before and after equilibration with saturated solutions in different solvents. Mixtures of Lewis base (dioxane and ethyl acetate)
and amphiprotic solvents (ethanol and water) were prepared for evaluating the influence of both nature and polarity of the
solvents. Solid-state analysis performed on the original samples (commercial products) made it possible to establish that
paracetamol, mefenamic acid and flufenamic acid were in their respective Form I. No polymorphic modifications are known for
niflumic acid. Paracetamol, niflumic and mefenamic acids did not show any change after equilibration with the various solvents
or solvent mixtures, regardless of their different chemical nature. In contrast, DSC, IR and X-ray analyses revealed the partial
recrystallization of flufenamic acid into its polymorphic Form III in solid phases at equilibrium with ethanol, ethyl acetate
and their blends, as well as in dioxane-water mixtures containing 30 to 100% dioxane and in ethanol-water mixtures with a
water content less than 50%.
Authors:M. Cirri, F. Maestrelli, S. Furlanetto, and P. Mura
Natural crystalline (α-, β-, γ-) and amorphous derivative (hydroxypropyl-β- and methyl-β) cyclodextrins were selected as potential
carriers for obtaining, through a co-grinding technique, a stable activated amorphous form of glyburide with improved dissolution
properties. Differential scanning calorimetry (DSC) was used to investigate solid-state modifications of the drug induced
by co-grinding with the selected carriers in a high energy vibrational micro-mill. X-ray powder diffraction and FTIR spectroscopy
were employed as additional techniques to support DSC data. Equimolar drug : cyclodextrin physical mixtures were co-ground
for different times (up to 60 min) at constant vibration frequency (24 Hz). A progressive drug amorphization with increasing
grinding time was observed in all binary systems, but, interestingly, different degrees of sensitivity to the mechanical-chemical
activation were evident. In fact, blends with natural cyclodextrins, despite the initial higher crystallinity than those with
the amorphous derivatives, required the same or shorter co-grinding times (60 min) to achieve complete drug amorphization.
Stability studies indicated no appreciable drug recrystallization in co-ground products after 4 months storage in sealed containers
at 25°C or 1 month at 25°C and 75% RH. No stability differences were detected between products with natural or derivative
cyclodextrins. The results accounted for the suitability of cyclodextrin co-grinding technique to obtain and stabilize glyburide
in the activated amorphous form.
Authors:P. Mura, F. Maestrelli, M. Cirri, S. Furlanetto, and S. Pinzauti
The interactions of trimethoprim, sulphadiazine and sulphamethoxazole with natural (a- b-, g- ) and amorphous (RAMEB) or crystalline
(DIMEB) methylated b-cyclodextrins were investigated both in aqueous solution (using phase-solubility analysis) and in the
solid state (using DSC supported by X-ray analysis). In particular, DSC studies enabled determination of the relative degree
of crystallinity of each drug in its physical and ground mixtures with the different cyclodextrins on the basis of the variation
of its heat of fusion in comparison with that of the pure drug. In all cases, the host cavity size was a prevalent factor
for the inclusion complexation in liquid state. On the contrary, it had a negligible effect on solid-state interactions in
terms of drug amorphization. DIMEB and RAMEB exhibited similar performances in aqueous solution, showing that the presence
of methyl-groups improved the complexing and solubilizing properties of b-cyclodextrin. However, DSC studies revealed that
RAMEB was clearly more active in performing solid-state interactions, i.e. drug amorphization, and as stabilizing agent for
the amorphous state brought forth.
Authors:A. Swiderski, A. Wojtal, P. Muras, A. Mikulko, S. Wrobel, and H. Koloczek
method was used to study phase transitions in Rhododendron
L. leaf tissues caused by temperatures below the freezing point of water.
The curves show several stages of water crystallisation, demonstrating that
these processes do not occur simultaneously in various types of cell organelles.
Temperatures and enthalpies of the phase transitions were determined and significant
changes were found in the DSC curves when the sample was repeatedly subjected
to sub-zero temperature cooling and heating. Also, frost resistance of the
same rhododendron taxons was studied by conductometric analysis and the DSC
results were compared with the data from other laboratory studies.