Method for the development of topical medicinal aerosols using liquified hydrocarbon gas.

Low chain liquid hydrocarbons (LH) at room temperature and atmospheric pressure can be used to simulate the effect of gas hydrocarbons (GH) in aerosol systems without the need of using pressured flasks. Samples of different tetracycline formulations were tested with LH and GH in order to study their behaviour and physicochemical stability in the system. The results showed a similar behaviour between samples when LH or GH were used, suggesting the use of LH to simulate the effect of GH introduction in the system, as a useful predictive method for the development of pressured aerosol formulations without using pressured containers in early steps of the process, such as pre-formulation studies.

Influence of the solvent system on the stability of doxycycline solutions.

Concentrated solutions of doxycycline are often added to drinking water of animals for oral antibiotic therapy. However, stability concerns of doxycycline in solution involve an accurate selection of the solvent system to ensure that the active substance will remain within the acceptance range during the product shelf-life and to avoid sub-therapeutic dosage. Different solvent systems have been evaluated in order to determine their influence on the stability of concentrated doxycycline solutions. The results showed differences in the degradation kinetics of doxycycline depending on the co-solvent used and they permitted to select a solvent system for liquid doxycycline hyclate formulations with low rate of degradation even after several months of storage. So, the inclusion of ethanol together with propylene glycol as main excipient was found to be beneficial, while no benefit was observed concerning the addition of citric acid. Once administered to drinking water, the solutions were stable for 24 h with no influence of the solvent system.

Serum-liposome interaction is an oxygen-dependent process.

Measurements of heat dissipation, oxygen concentration and average vesicle size were correlated to study the effect of serum components on different types of liposome. The results indicate that the interaction between serum components and liposomes is exothermic and oxygen dependent, and leads to disruption of vesicles. The dependence of this effect on serum concentration, vesicle surface charge and type of liposome was also evaluated. Serum components did not produce any effect on conventional liposomes in the absence of oxygen. Moreover, in hypoxic conditions the serum-liposome interaction was delayed. Both results suggest that this interaction is an oxygen-dependent event. Finally, we confirmed that sterically stabilised liposomes remain unalterated in the presence of serum.

Chemical degradation of liposomes by serum components detected by NMR.

Interaction between serum components and liposomes is an oxygen-dependent exothermic process. We studied the interaction of 100 nm extruded liposomes (bearing positive, negative or no charge) with foetal calf serum by 1H NMR and 13C NMR, in order to further our understanding of these reactions. Studies of aqueous or organic extracts obtained after 2 h, 1 day or 1 week, showed hydrolysis to be a degradation process concomitant with the interaction with serum. Oxidation was identified as additional to hydrolysis in the process of degradation. Oxidation produced aldehydes, acids and alcohols, although aldehydes and alcohols were prone to further decomposition and only appeared transiently. Alkenes and other oxidized compounds predominated in those products derived from oxidation. In stearylamine-containing liposomes some aldehydes and a nitroderivative were found as degradation products. Such metabolites are apolar and their presence might explain the intrinsic toxicity of this kind of liposome in cell cultures. The work described in the present study revealed the chemical degradation of liposomes in the serum used. In all cases the results obtained were compared with liposomes not incubated with serum.

Design and applications of a new fluorimetric assay of thioguanine in liposomes.

This paper describes the systematic design of a modification that overcomes the difficulties encountered with the original fluorimetric method for thioguanine. It allows the determination of thioguanine alone, as well as in a lipid medium (specifically in liposomes). It consists of an earlier lipid extraction based on liquid-solid extraction cartridges; then the oxidation of thioguanine in the lipid-free solution is performed by adding hydrogen peroxide in pH 4.7 acetate buffer at 50 degrees C for 30 min. A central composite design was used to finally optimize the method. The assay is precise (RSD values were 1.8 and 2.1% for intra-day and between-day precision, respectively). The detection limit was 0.05 microM and the limit of quantitation 0.08 microM.

Characterization of alginate beads loaded with ibuprofen lysine salt and optimization of the preparation method.

The parameters influencing alginate ionotropic gelation and the production of alginate beads loaded with hydrosoluble ibuprofen lysine salt (IBU-L) were studied, as well as the optimization of the method for its attainment. A three-factor and three-level factorial design (3(3)) was carried out to determine the influence of three experimental variables: polymer concentration, CaCl2 concentration, and curing time on the dependent variables drug load and encapsulation efficiency. The effect of the pH used in the preparation bath was also evaluated. Concentrations of CaCl2 and pH of gelling bath were seen to affect bead formation and stability as well as their ability to properly entrap the drug. In this work, IBU-L was used as a model of a non-steroidal anti-inflammatory drug with good solubility in alginate solutions. IBU-L was successfully encapsulated in alginate beads obtained by the ionotropic gelation method. The obtained alginate matrixes are able to modify the release of the entrapped IBU-L and this occurs in a pH-sensitive way that can be correlated with the swelling behaviour of the alginate-produced beads. Morphological characteristics were evaluated by means of scanning electron microscopy.