Authors:Irene Pasquali, R. Bettini, and F. Giordano
This work aims to investigate the thermal behaviour of diclofenac, diclofenac sodium, and NaHCO3 both as single components and binary mixtures. In particular, the melting point and latent heat of fusion binary diagrams
of the diclofenac sodium/diclofenac mixtures at different mole fraction compositions were investigated in order to gain information
about the thermal behaviour of their solid mixtures. A good agreement between liquidus curves, calculated by the Schroeder-Van
Laar equation from fusion enthalpies and temperatures, and the experimental results was found. For all binary compositions,
an endothermic effect at 153�C, probably due to the eutectic fusion, is present.
Authors:F. Giordano, A. Rossi, R. Bettini, A. Savioli, A. Gazzaniga, and Cs. Novák
The thermal behavior of binary mixtures of paracetamol and a polymeric excipient (microcrystalline cellulose, hydroxypropylmethylcellulose
and cross-linked poly(vinylpyrrolidone)) was investigated. The physical mixtures, ranging from 50 to 90% by mass of drug,
were submitted to a heating-cooling-heating program in the 35–180C temperature range. Solid-state analysis was performed
by means of differential scanning calorimetry (DSC), hot stage microscopy (HSM), micro-Fourier transformed infrared spectroscopy
(MFTIR), and scanning electron microscopy (SEM).
The polymeric excipients were found to address in a reproducible manner the recrystallization of molten paracetamol within
the binary mixture into Form II or Form III. The degree of crystallinity of paracetamol in the binary mixtures, evaluated
from fusion enthalpies during the first and second heating scans, was influenced by the composition of the mixture, the nature
of the excipient and the thermal history. In particular, DSC on mixtures with cross-linked poly(vinylpyrrolidone) and hydroxypropylmethylcellulose
with drug contents below 65 and75%, respectively, evidenced the presence only of amorphous paracetamol after the cooling phase.
Microcrystalline cellulose was very effective in directing the recrystallization of molten paracetamol as Form II.
Authors:A. Cvetkovskii, R. Bettini, Lj. Tasic, M. Stupar, I. Casini, A. Rossi, and F. Giordano
The thermal behaviour of binary mixtures between β-cyclodextrin (β-CD) and either carbamazepine polymorphic Form I (CBZ I),
Form III (CBZ III) or dihydrate was investigated in order to assess possible interactions of CBZ solid phases with β-CD. Physical
mixtures and kneaded binaries of β-CD and different CBZ crystal forms were studied by differential scanning calorimetry, thermogravimetric
analysis and hot stage microscopy. The pattern of transition of CBZ Form III into Form I is strongly influenced by β-CD. The
liquid-solid transition is practically absent when anhydrous CBZ/β-CD mixes are tested, as a consequence of an interaction
between β-CD and liquid CBZ that hinders CBZ recrystallisation as Form I occurring after CBZ Form III melting.
Water loss on heating of CBZ dihydrate in the presence of β-CD leads in all cases to the formation of CBZ Form I.
Authors:R. Bettini, G. Bertolini, E. Frigo, A. Rossi, I. Casini, I. Pasquali, and F. Giordano
The aim of this work was to study the solubility in supercritical CO2 of the hydrated phase of three model drugs, namely theophylline, carbamazepine, and diclofenac sodium, in comparison with
the respective anhydrous form. Possible solid-state modifications, stemming from the interaction with supercritical CO2, were investigated by differential scanning calorimetry, thermogravimetric analysis, hot stage microscopy, Fourier Transform
infrared spectroscopy and Karl-Fischer titrimetry. It was found that all three pharmaceutical hydrates exhibited higher solubility
in supercritical CO2 than the relevant anhydrous phases. In the case of theophylline monohydrate, the instability of the crystal phase at the
experimental temperature adopted has been evidenced. Diclofenac sodium tetrahydrate represents a peculiar case of chemical
interaction with the acid supercritical fluid, mediated by crystal water.
Authors:R. Bettini, A. Rossi, E. Lavezzini, E. Frigo, I. Pasquali, and F. Giordano
Aim of this work was to investigate the solid-state characteristics of micronized acetylsalicylic acid (ASA), produced by
rapid expansion of a supercritical carbon dioxide solution (RESS) and to assess whether a correlation could be found between
process parameters and solid-state characteristics. Drug solubility in supercritical CO2 was first assessed under various pressure and temperature conditions. DSC, FT-IR, PXRD, SEM, laser light scattering and HPLC
were used to characterise the solid phases produced by the RESS. The obtained particles were crystalline, with spectroscopical
and diffractometrical pattern overlapping those of the starting available product. However, a strong reduction of particle
size was obtained, linearly correlated to pressure imposed during the RESS process, while temperature did not seem to have
a major effect. Similar influence of pressure was observed on the final melting temperature of the micronized ASA. The application
of a mathematical model allowed to conclude that the melting temperature depression of RESS-prepared ASA powders can be attributed
to the decrease of particle dimension rather than to the formation of different solid phases or impurities.
Authors:F. Giordano, A. Rossi, I. Pasquali, R. Bettini, E. Frigo, A. Gazzaniga, M. Sangalli, V. Mileo, and S. Catinella
The thermal behaviour of Diclofenac was investigated using Differential Scanning Calorimetry, Hot Stage Microscopy, and Thermogravimetric
Analysis. A discrepancy was observed between the melting point values recorded under dynamic flow of either dry nitrogen (180C)
or air (160C). By means of High Performance Liquid Chromatography/Mass Spectrometric analyses, it has been possible to ascribe
this difference in melting points to the formation of three degradation products as a result of intramolecular cyclization
and condensation reactions during the heating process in an oxidative atmosphere.