Characterization of ternary phase diagrams by means of thermal and rheological analyses.

CONTEXT: Mixtures made of oil, water and surfactants give rise to a wide range of structure with different characteristics and phase manifestations. OBJECTIVE: Aim of this paper is to build up and understand the phase diagram of a model ternary system (Water, Polysorbate 80 and isopropyl myristate) by the use of common techniques such as thermal analysis and rheology, in comparison with visual assessment and polarized light microscopy. METHODS: Different ternary systems were prepared and analyzed by means of DSC and rheology in order to highlight the state of water (free, interphasal, bound water) and the samples structural characteristics. RESULTS: The resultant phase diagram is divided into four different zones. Bound water zone is predominant at elevated surfactant/oil ratios, while as the surfactant/oil ratio decreases, DSC reveals the presence of free water. Interphasal water prevails at intermediate water and surfactant content which corresponds with gels systems. Mechanical spectra allow to discern between cubic (true gel) and lamellar mesophases (weak gel), while flow curves allow to distinguish among microemulsions, emulsions or lamellar mesophases. DISCUSSION: A deeper characterization of a model ternary phase diagram is possible, with respect to the simple visual inspection, by the use of thermal analysis and rheology. The state of water molecules and the viscoelastic characteristics of the system allow to obtain important structural considerations. CONCLUSIONS: In conclusion, the knowledge of the state of water and of the viscoelastic characteristics of the systems allow a deeper understanding of the structural features of the ternary phase diagram.

Poloxamer thermogel systems as medium for crystallization.

PURPOSE: To prepare a thermoreversible gel system able to work as a medium for crystallization at around 20°C, allowing easy retrieval of crystals by simply decreasing the gel temperature. Lactose was selected has model substance for crystallization. METHODS: Water solutions with different% of poloxamer 407, α-Lactose monohydrate, and ethanol were prepared and analysed by rheology to understand how the different components alter the gelling temperature. The systems with the required characteristics for lactose crystallization were prepared and the crystals recovered by cooling and then filtering the dispersion. RESULTS: Rheological analysis showed interaction between the poloxamer and lactose. Increasing the quantity of poloxamer or lactose lowered the gelation temperature while the addition of small amounts of ethanol had a modest effect on the same property. These data were used to identify the ideal concentration of the components in order to prepare a system matching the features of our purpose. Such system yielded high quality crystals, with well-defined geometry and narrow particle size distribution. CONCLUSION: Poloxamer is a very interesting polymer in that it is able to generate a reversible gelling medium from which crystals can be harvested by filtering, without the addition of any chemicals to promote the sol-gel transition.

Evaluation of polymer mucoadhesiveness by the use of acoustic spectroscopy.

An innovative and simple methodology has been developed and used for the evaluation of mucoadhesive properties of several polymers by means of sound speed measurements using high-resolution acoustic spectroscopy. In systems made of polymers in water, variations in hydration shell of polymeric chains determine changes of dispersions compressibility, and this phenomenon can be monitored by sound speed measurements. Four different polymers have been selected, namely PEG 6000, Carbopol 974, HPMC K4M, and Pectin 200/USP, all characterised by very different mucoadhesive properties. Samples made of each polymer alone (0.3-1.0% w/w) or in mixture with mucin (mucin fixed at 1.0% w/w) in water were investigated while using high-resolution ultrasonic spectrometer at two different frequencies (5.2 and 8.2 MHz). Polymer-mucin interaction was evaluated comparing experimental sound speed values of polymer-mucin samples with their theoretical values derived from the addition of sound speeds obtained while analysing each component alone. Results demonstrated the ability of the acoustic method to discriminate between mucoadhesive and no mucoadhesive polymer-mucin dispersions and allowed also the comparison between their mucoadhesive strengths. The study has therefore demonstrated the potential of using high-resolution ultrasonic spectroscopy to evaluate the polymers' mucoadhesiveness, with the great advantage of testing small amount of samples even if opaque.

The use of acoustic spectroscopy in the characterisation of ternary phase diagrams.

This study shows novel and interesting applications of acoustic spectroscopy for characterisation of ternary systems such as isopropylmiristate (IPM)/polysorbate 80 (T)/water (W). Particle size and microrheological extensional moduli (i.e. G' and G″) of different systems were determined by means of acoustic parameters such as sound attenuation and speed. Electric conductivity was also measured using the same instrument. The ultrasonic profile in terms of attenuation and sound speed in the megahertz frequency range, allowed the characterisation of the different zones of the ternary diagram such as microemulsion, emulsion and gel zones, as well as the evaluation of water state and particle size. This last parameter is a very effective tool in quantifying the phase transitions of systems and understanding which system is formed in any phase diagram zone. In fact, it is possible to analyse samples without dilution and despite their degree of turbidity, allowing complete characterisation of both properties and structure.

A study on the stability and enzymatic activity of yeast alcohol dehydrogenase in presence of the self-assembling block copolymer Poloxamer 407.

Yeast alcohol dehydrogenase (ADH) is an enzyme widely studied for biotechnological applications due to its involvement in fermentation industry, and various attempts to improve its catalytic properties and its thermal stability have been carried out. In this paper, the influence of a block copolymer (Poloxamer 407) on ADH enzymatic activity and thermal behaviour has been studied in order to get new insights about the use of poloxamers in formulation of sustained release systems for therapeutic proteins. Poloxamer 407 has the ability to form micelles and gel due to its self-assembling and thermoresponsive properties. The effect of the copolymer towards thermal stress and pH changes, which often reduce enzymes activity it has been investigated by means of enzymatic assays and differential scanning calorimetry. Results showed that at pH 9.1 and 7.3, the Poloxamer in the form of unimeric, micellar and gel state is able to effectively preserve the enzyme from thermoinactivation. In addition by calorimetric data Poloxamer 407 has showed an effect in preserving ADH from aggregation at pH 7.3. In conclusion, Poloxamer 407 seems to be very effective in protecting ADH from stress related events, like alkaline inactivation and aggregation.

Dynamic mechanical thermal analysis of hypromellose 2910 free films.

It is common practice to coat oral solid dosage forms with polymeric materials for controlled release purposes or for practical and aesthetic reasons. Good knowledge of thermo-mechanical film properties or their variation as a function of polymer grade, type and amount of additives or preparation method is of prime importance in developing solid dosage forms. This work focused on the dynamic mechanical thermal characteristics of free films of hypromellose 2910 (also known as HPMC), prepared using three grades of this polymer from two different manufacturers, in order to assess whether polymer chain length or origin affects the mechanical or thermo-mechanical properties of the final films. Hypromellose free films were obtained by casting their aqueous solutions prepared at a specific concentrations in order to obtain the same viscosity for each. The films were stored at room temperature until dried and then examined using a dynamic mechanical analyser. The results of the frequency scans showed no significant differences in the mechanical moduli E' and E″ of the different samples when analysed at room temperature; however, the grade of the polymer affected material transitions during the heating process. Glass transition temperature, apparent activation energy and fragility parameters depended on polymer chain length, while the material brand showed little impact on film performance.

Monitoring the aggregation behaviour of self-assembling polymers through high-resolution ultrasonic spectroscopy.

Poloxamer 407 is a well-known self-assembling polymer with a wide range of temperature- and concentration-dependent phase behaviour, such as micellization and gelation. This work was carried out to demonstrate the potential of high-resolution ultrasonic spectroscopy in evaluating aggregation-deaggregation behaviour of self-assembling polymers. In order to achieve this objective, six different concentrations of Poloxamer 407 water dispersion were prepared and analysed between 5 and 35 degrees C using ultrasonic spectroscopy. For comparison, the same samples were also analysed by the DSC technique. The results showed that polymer aggregation process can be successfully monitored using both ultrasonic parameters of sound speed and attenuation. Furthermore, good agreement with DSC data was observed in terms of characteristic transition temperatures and also in terms of micellization kinetics and related parameters.