On the dimorphism of prednisolone: The topological pressure-temperature phase diagram involving forms I and II.

The dimorphism of the corticosteroid anti-inflammatory drug prednisolone has been investigated by the construction of a topological pressure-temperature phase diagram, using crystallographic and calorimetric data. The system is enantiotropic, because the temperature of the I-II equilibrium under atmospheric conditions (400-463 K) is lower than that of the two melting equilibria (518.7 K for form II and 526.3 K for form I). The slope of the I-II equilibrium in the pressure-temperature phase diagram is negative and relatively steep; therefore, form II, which is the stable form at room temperature, will not easily encounter conditions where form I will become stable even under industrial processing conditions. On the other hand, extreme small amounts of form I have been observed to spontaneously transform into form II in a time interval of about six years at room temperature and it can be concluded that although form I is very persistent under ambient conditions, it does slowly convert into form II. Moreover, the system does not obey the density rule.

PLGA nanospheres for the ocular delivery of flurbiprofen: drug release and interactions.

Poly(D,L-lactide-co-glycolide) nanospheres incorporating flurbiprofen were prepared by the solvent displacement technique for purposes of assessing (i) drug-polymer physicochemical interactions, (ii) flurbiprofen release from the polymer matrix and (iii) eye permeation of the drug formulated in the colloidal system. The resulting nanospheres were on average 200-300 nm in size and bore a negative charge (xi-potential around -25 mV). They were shown by atomic force microscopy and transmission electron microscopy to be spherical and regular in shape. Thermal methods, infrared spectroscopy and X-ray diffraction showed that the drug was dispersed inside the particles. These tests evidenced an eutectic mixture meaning more widespread dispersion of the drug in the polymer system. Entrapped flurbiprofen was released in vitro from the polymer system by dissolution and diffusion in high drug loaded nanospheres, whereas those with a lesser load showed only diffusion. The ex vivo corneal permeation study showed that flurbiprofen-loaded nanospheres enhanced drug penetration by about twofold over commercial eye drops containing poly(vinyl alcohol) and by about fourfold over flurbiprofen in pH 7.4 phosphate buffer. The corneal hydration level of each cornea was determined to evaluate potential corneal damage.

Stability and in vitro drug release of flurbiprofen-loaded poly-epsilon-caprolactone nanospheres.

The effects of temperature and two different initial pH (2.67 and 7.00) on poly-epsilon-caprolactone (P epsilon CL) nanospheres loaded with flurbiprofen (FB) (aqueous suspensions) were studied to investigate their influence on the stability and physicochemical characteristics of these drug delivery systems. The drug release behavior was also studied. Release of the associated FB occurred very fast on high dilution in a buffered medium. The stability of the polymeric system depends on the temperature and the initial pH value; it is more degradable with the particles stored at 40 degrees C with an initial pH value of 2.67.

Flurbiprofen-loaded nanospheres: analysis of the matrix structure by thermal methods.

We report the preparation and evaluation of flurbiprofen loaded-poly-epsilon-caprolactone nanospheres obtained by solvent displacement method. Characterization by thermal methods, infrared spectroscopy and X-ray diffraction analysis can reveal the dispersion state of the drug inside the nanospheres. Such information predicts the stability of the particles and the drug release behaviour. The study has indicated the presence of a molecular dispersed system. In addition, construction of a phase diagram has allowed us to determine the drug/polymer ratios at which flurbiprofen has the highest entrapment efficiency.

An investigation of FB interactions with poly(ethylene glycol) 6000, poly(ethylene glycol) 4000, and poly-epsilon-caprolactone by thermoanalytical and spectroscopic methods and modeling.

The interactions between flurbiprofen (FB) and different polymers are studied in order to improve the bioavailability of FB. FB-polymer phase diagrams [poly(ethylene glycol) (PEG) 4000, PEG 6000, and poly-epsilon-caprolactone] were constructed and compared with the modeling diagrams. Thermoanalytical methods (differential scanning calorimetry, thermomicroscopy) were used to construct the phase diagrams. Thermodynamic data were used to model the FB-polymer systems. The construction of the FB-polymer phase diagrams showed the existence of a stable invariant called "eutectic" characterized by (XE)exp, (TfE)exp, and (DeltaHfE)exp, the experimental eutectic composition, the experimental temperature, and the enthalpy of eutectic melting, respectively. Modeling confirmed the values for these parameters and was used to evaluate the different Flory-Huggins parameters chi for each FB-polymer mixture. chi values and the infrared spectra confirm that the interactions due to hydrogen bonds between FB and PEG 4000 are more numerous than between FB and PEG 6000 and also more numerous than between FB and poly-epsilon-caprolactone.