Effect of water-soluble polymers, polyethylene glycol and poly(vinylpyrrolidone), on the gelation of aqueous micellar solutions of Pluronic copolymer F127.

The micellization of F127 (E(98)P(67)E(98)) in dilute aqueous solutions of polyethylene glycol (PEG6000 and PEG35000) and poly(vinylpyrrolidone) (PVP K30 and PVP K90) is studied. The average hydrodynamic radius (r(h,app)) obtained from the dynamic light scattering technique increased with increase in PEG concentration but decreased on addition of PVP, results which are consistent with interaction of the micelles with PEG and the formation of micelles clusters, but no such interaction occurs with PVP. Tube inversion was used to determine the onset of gelation. The critical concentration of F127 for gelation increased on addition of PEG and of PVP K30 but decreased on addition of PVP K90. Small-angle X-ray scattering (SAXS) was used to show that the 30 wt% F127 gel structure (fcc) was independent of polymer type and concentration, as was the d-spacing and so the micelle hard-sphere radius. The maximum elastic modulus (G(max)(')) of 30 wt% F127 decreased from its value for water alone as PEG was added, but was little changed by adding PVP. These results are consistent with the packed-micelles in the 30 wt% F127 gel being effectively isolated from the polymer solution on the microscale while, especially for the PEG, being mixed on the macroscale.

The effect of polymeric additives on the solubilisation of a poorly-soluble drug in micellar solutions of Pluronic F127.

The solubilisation of griseofulvin in 1wt% aqueous micellar solutions of Pluronic F127 at 37°C has been modified by adding polyethylene glycol PEG 35000 or poly(vinylpyrrolidone) PVP K30. The solubilisation capacity expressed in terms of unit weight of F127 is increased by the addition of 0.5wt% PEG 35000 to a value approaching double that of a 2.5wt% solution of F127 alone, but there is no advantage in adding 0.5wt% PVP K30.

The effect of n-, s- and t-butanol on the micellization and gelation of Pluronic P123 in aqueous solution.

In dilute aqueous solution unimers of copolymer P123 (E(21)P(67)E(21)) associate to form micelles, and in more concentrated solution micelles pack to form high-modulus gels. We are interested in the use of the system as a templating agent in the synthesis of mesoporous materials, and the possibility of determining gel structure, hence mesoporosity, by use of n-, s- or t-butanol. Dynamic light scattering from clear dilute solutions has been used to confirm micellization, visual observation of mobility (tube inversion) to detect gel formation in concentrated solutions, oscillatory rheometry to confirm gel formation and provide values of elastic moduli over a wide temperature range, and small-angle X-ray scattering to determine gel structure. As expected, clear cubic gels (fcc) formed at moderate concentrations and temperatures, e.g. 30 wt.% P123, 20°C, and clear hexagonal gels at higher concentrations and temperatures. The transition on heating from cubic to hexagonal gel involved an intermediate turbid phase in which cubic and hex structures coexisted. Considering cubic gels of 35 wt.% P123 in 5 wt.% butanol/water, those in n-butanol/water had the lowest critical temperatures for gel formation and the highest maximum values for the dynamic elastic modulus (G') of the gels, a result consistent with n-butanol/water being the poorest solvent for P123.

Micellization and gelation of mixed copolymers P123 and F127 in aqueous solution.

The micellization in dilute aqueous solution of Pluronic copolymers P123 (E21P67E21) and F127 (E98P67E98) and mixtures of the two was investigated using static and dynamic light scattering. Gelation of concentrated solutions of the two copolymers and their mixtures was studied using tube inversion and oscillatory rheometry. The two copolymers comicellized to give micelles with narrow size distributions. Clouding temperatures and critical micelle temperatures decreased as the proportion of P123 in the mixture was increased. Micelle association numbers of the mixed micelles lay between the values found for micelles of P123 and F127 alone, whereas micelle radii passed through maximum values in the range 0-50 wt % P123. As judged by the ratio of the thermodynamic to the hydrodynamic radius, the micelle interaction potential changes gradually from soft to hard as the proportion of P123 in the mixture is increased. Regions of cubic and hexagonal (birefringent) gel were defined for concentrated solutions. The high-temperature boundary of the 30 wt % cubic gel decreased monotonically from 90 to 43 degrees C as the proportion of P123 in the mixture was increased from 0 to 100 wt %, whereas the low-temperature boundary was essentially constant at 15 +/- 3 degrees C. Increasing the proportion of P123 in the mixture at 25 degrees C increased the concentration at which the cubic gel was first formed and decreased the concentration at which the hexagonal gel was first formed.

Mixtures of triblock copolymers E(62)P(39)E(62) and E(137)S(18)E(137) potential for drug delivery from in situ gelling micellar formulations.

The gelation behaviour of concentrated micellar solutions of mixtures of a block copolymer of ethylene oxide and styrene oxide (E(137)S(18)E(137)) with one of ethylene oxide and propylene oxide (E(62)P(39)E(62)) has been investigated. Over a wide range of compositions, up to 90 wt.% E(137)S(18)E(137) in the mixture, gelation resembled that of solutions of E(62)P(39)E(62) alone, i.e. they gelled on heating from ambient to body temperature. In related experiments, using the aromatic drug griseofulvin as a comparative standard, it was demonstrated that solubilisation efficiency of dilute micellar solutions of the mixtures with 80 wt.% or more E(137)S(18)E(137) approached that of solutions of E(137)S(18)E(137) alone. Thus it was shown that the mixed system could have both the satisfactory solubilisation capacity of micellar solutions of E(137)S(18)E(137) and the desirable gelation characteristics of E(62)P(39)E(62), and so have potential for use in drug release applications involving in situ gelation.