In this study two solubility-parameter models have been compared using as dependent variables the logarithm of the mole fraction solubility, lnX2e, and ln(alpha)/U (originally used in the extended Hansen method), where alpha is the activity coefficient and U is a function of the molar volume of the solute and the volume fraction of the solvent. The results show for the first time the proton-donor and -acceptor hydrogen-bonding capacities of paracetamol, as measured by the acidic and basic partial-solubility parameters. The influence of solvents on the differential scanning calorimetry (DSC) pattern of the solid phases was also studied in relation to the solubility models tested. Citric acid was chosen as a test substance because of its high acidity and its proton donor capacity to form hydrogen bonds with basic solvents. The partial acidic and basic solubility parameters obtained from multiple regression were consistent with this property, validating the model chosen. The results show that the more direct lnX2e variable was more suitable for fitting both models, and the four-parameter model seemed better for describing the interactions between solvent and solute.

Poly(methylidene malonate 2.1.2.) (PMM 2.1.2.) nanoparticles were prepared in phosphate buffer through emulsion polymerization of monomeric units; the kinetics of the reaction was monitored by spectrophotometry at 400 nm. Average nanoparticle sizes, molecular weights, and biodegradability of this potential drug carrier were determined under various conditions. As previously demonstrated for other similar monomers, i.e. IHCA or IBCA, pH influenced the physico-chemical characteristics of the nanoparticles obtained. Ethanol release from the ester-bearing side chains indicated that the polymers were susceptible to hydrolysis when incubated in basic pH or in rat plasma. A secondary degradation pathway, yielding formaldehyde through a reverse Knoevenagel's reaction, was minimal. Cytotoxicity studies of this new vector, in vitro, against L929 fibroblast cells demonstrated that PMM 2.1.2. nanoparticles were better tolerated than other poly(alkylcyanoacrylate) (PACA) carriers. Pharmacokinetic studies were also carried out to observe the fate of 14C-labelled PMM 2.1.2. nanoparticles after intravenous administration to rats. Forty eight hour post-injection, more than 80% of the radioactivity was recovered in urine and faeces. The body distribution of the polymer was estimated by measuring the radioactivity associated with liver, spleen, lung and kidneys. Five minutes after injection, a maximum of 24 +/- 2% of the total radioactivity was detected in the liver and less than 0.4% in the spleen. The liver-associated radioactivity decreased according to a biphasic profile and less than 8% of the total radioactivity remained after 6 days.

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