Rafael Barreiro-Iglesias

Incorporation of small quantities of surfactants as a way to improve the rheological and diffusional behavior of carbopol gels

This paper analyzes the effects of Tween 80, Pluronic F-127, sodium dodecylsulfate (SDS), and benzalkonium chloride on the macro and microviscosity of Carbopol 934NF (0.25-0.50 g/dl) pharmaceutical gels. Carbopol/surfactant interactions, which were reflected in changes in the intrinsic viscosity of the polymer and in shifts of IR spectra bands of films, considerably modified the rheological properties of the gel (flow and oscillatory rheometry) and the diffusion coefficients of polystyrene particles (dynamic light scattering, DLS). At pH 4, any surfactant at a concentration of 0.01 g/dl promoted interpolymer connections producing an open three-dimensional network with maximum viscous and elastic moduli, which does not disturb the diffusive movement of polystyrene particles. An increase in non-ionic surfactant (0.05-0.50 g/dl) gradually decreased viscosity and elasticity since there were more surfactant molecules to surround each carbopol particle, forming intrapolymeric micelles and breaking the interpolymer connections. This macroscopic effect is, however, not reflected in a decrease but in an increase in microviscosity (estimated by DLS) owing to the formation of larger carbopol/surfactant aggregates and free micelles that contribute significantly to the obstruction of the diffusional path. Both ionic surfactants decreased macroviscosity owing to ionic aggregation (benzalkonium chloride) or increase in ionic strength (mainly SDS), while the repercussion on the diffusion of polystyrene particles was dramatically different, and was hindered (due to the carbopol/surfactant aggregates) or enhanced (due to the shrinking of carbopol microgels), respectively. At pH 7.4, the ionization of the carboxylic groups produced an expansion of the polymer chains accompanied by a huge increase in viscosity and elasticity and a decrease in diffusion coefficients in comparison with those obtained at pH 4. The effects of the surfactants were similar to those observed at pH 4 but less intense. Chloramphenicol release studies (Franz-Chien cells) revealed that 0.01 g/dl surfactant did not affect the diffusion while a change in pH dramatically altered the process. The results show that by choosing the appropriate proportion of the most suitable surfactant, it is possible to modulate the flow behavior, elastic properties, and diffusional microenvironment of carbopol gels, without losing the pH-dependent gelling ability, which could improve the suitability of carbopol gels for drug delivery through different routes.

Thermal and FTIR Characterization of Films Obtained From Carbopol/Surfactant Aqueous Solutions

The suitability of differential scanning calorimetry (DSC) as a routine technique to characterize polymer/surfactant interactions in aqueous medium was evaluated in films obtained by evaporation of binary aqueous mixtures of Carbopol® 934, a cross-linked poly(acrylic acid), and Tween 80, Pluronic F-127 (non-ionic surfactants), sodium dodecylsulphate (SDS, anionic surfactant), or benzalkonium chloride (cationic surfactant). In all cases, the interactions that occur at specific proportions of both components, as shown in the FTIR spectra, could be detected by shifts of some melting peaks. Lorentzian deconvolution of carbopol carbonyl groups (1690–1730 cm−1) was used to quantify the intensity of the interaction between the polymer and the non-ionic surfactants. DSC curves revealed the compatibility of carbopol with Tween 80 or SDS, and its strong affinity for Pluronic F-127 or benzalkonium chloride. This surfactant binds electrostatically to carbopol causing the formation of an insoluble polyelectrolyte complex, the composition and thermal behavior of which are very different from those of the films obtained from the supernatant.

Controlled Release Camptothecin Tablets based on Pluronic and Poly(acrylic acid) Copolymer. Effect of Fabrication Technique on Drug Stability, Tablet Structure, and Release Mode

ABSTRACT Poly(ethylene oxide)-b-poly(propylene oxide)-b-(polyethylene oxide)-g-poly(acrylic acid), a graft-comb copolymer of Pluronic® 127 and poly(acrylic acid) (Pluronic-PAA), was explored as an excipient for tablet dosage form of camptothecin (CPT). The tablets were prepared by either direct compression of the drug-polymer physical blend, suspension in ethanol followed by evaporation, or compression after kneading and characterized with respect to their physical structures, drug stability, and release behavior. Porosity and water uptake rate were strongly dependent on the fabrication procedure, ranking in the order: direct compression of physical blend > compression after suspension/evaporation in ethanol > compression after kneading. Tablets prepared by compression of physical blends swelled in water with a rapid surface gel layer formation that impeded swelling and disintegration of the tablets core. These tablets were able to sustain the CPT release for a period of time longer than those observed with the tablets made by either suspension/evaporation or kneading, which disintegrated within a few minutes. Despite the tablet disintegration, the CPT release was impeded for at least 6 hr, which was attributed to the ability of the Pluronic-PAA copolymers to form micellar aggregates at the hydrated surface of the particles. Physical mixing did not alter the fraction of CPT being in the pharmaceutically active lactone form, whilst the preparation of the tablets by the other two methods caused a significant reduction in the lactone form content. Tablets prepared from the physical blends demonstrated CPT release rates increasing with the pH due to the PAA ionization leading to the increase in the rate and extent of the tablet swelling. The results obtained demonstrate the potential of the Pluronic-PAA copolymers for the oral administration of chemotherapeutic agents.

Microcalorimetric evidence and rheological consequences of the salt effect on carbopol-surfactant interactions

The aggregation process of Carbopol 934NF, a Food and Drug Administration approved cross-linked poly(acrylic acid) commonly used in pharmaceutical technology, with nonionic and ionic surfactants in 0.9% NaCl dispersions and artificial lacrimal fluid was analyzed using titration microcalorimetry and rheometry. Titration microcalorimetry experiments indicated that the interaction processes in 0.9% NaCl are thermodynamically similar to those in water, although slightly less intense. In contrast, in artificial lacrimal fluid the carbopol-surfactant interactions were hindered. Carbopol association with Tween 80 (exothermic) or Pluronic F-127 (endothermic) occurs through hydrogen-bonding interactions, which are scarcely debilitated in 0.9% NaCl but strongly impeded in artificial lacrimal fluid. In this medium, the higher pH causes more carboxylic acid groups to become ionized, and the presence of calcium ions blocks them partially. In 0.9% NaCl, there is a shielding effect of the ionic groups of the polymer that promotes the hydrophobic association with sodium dodecyl sulfate and makes the complex formation with benzalkonium chloride more difficult. In both cases, the processes were exothermic. In artificial lacrimal fluid, the interaction with sodium dodecyl sulfate disappears while an endothermic association with benzalkonium chloride takes place. The ion-induced changes in the intensity of the carbopol-surfactant association are reflected in the rheological behavior of the 0.25% acrylic polymer dispersions. The results show that the nature and concentration of ions may have a strong influence on the design and on the physiological behavior of drug delivery systems based on carbopol gels.