Colloidal Stability of a Pharmaceutical Latex: Experimental Determinations and Theoretical Predictions

already been published concerning the use of insoluble polyIn this work, the colloidal stability of a pharmaceutical ethylcelmers as drug vehicles in very different fields, such as ophlulose latex, Aquacoat, is analyzed by means of turbidity measurethalmology (1), immunology (2), or cancer treatment (3, ments. The effects of both electrolyte (KCl, CaCl2 and LaCl3) 4). Although the colloidal behavior of polymer colloids has concentration and pH on the stability are considered, and it is been thoroughly investigated for over 30 years, the rigorous found that at pH 4 (6) , the critical coagulations concentrations requirements concerning toxicity and biodegradability, when (c.c.c.) are 70 (150) mM KCl, 12 (20) mM CaCl2 , and 1 (1) mM dealing with the pharmaceutical applications of these materiLaCl3 . The results are interpreted in terms of both classical and als, limit the number of polymers that can be considered extended versions of the DLVO theory of the stability of colloids; candidates to be used as drug transport substrates. One of the Hamaker constant, A , characteristic of the van der Waals interaction between the particles in suspension, is calculated from them appears to be Aquacoat, an ethylcellulose latex, commeasurements of the surface free energy of the polymer, based on mercially available and often used in pharmaceutical applicontact angle measurements of selected liquids on polymer pellets. cations; we have studied some of its surface properties in Concerning the electrostatic contribution to the total interaction previous works (5–7). energy between the polymer spheres, it is calculated from zeta In this work, we will focus on the stability of Aquacoat potential data deduced from electrophoretic mobility of the latex latex. Among the various forms in which pharmaceutical suspensions. The application of the so-called extended DLVO theproducts can be prepared for their administration, suspenory includes not only van der Waals and electrostatic interactions, sions are the most problematic as to their stabilization; even but also acid–base or structural ones, estimated using a recent the measurement of the stability of pharmaceutical dispermodel of the surface free energy of solids. Using the well-known sions is one of the most difficult problems faced by medicine Fuchs equation, we have computed the stability ratio W of the designers. Such measurements should allow one to predict suspensions, using both the classical and extended DLVO theories, for the different experimental conditions. The results show that, the useful shelf-life of the preparation and to specify the when the electrolyte is KCl, the classical model correctly predicts design requirements to achieve that stability. the c.c.c. values, although the slopes of the log W concentration However, in addition to these practical reasons, there are trends are different from the experimental ones. The extended also fundamental justifications for the need of a deep undertheory underestimates the c.c.c.’s and gives a better approximation standing of the thermodynamics and the interfacial properto the slopes. In the case of both CaCl2 and LaCl3 , the best ties of these systems. Hence, the aim of this work is to agreement is always found with the extended theory. It is sugcharacterize the stability of Aquacoat suspensions, both exgested that consideration of ionic strength effects on the acid– perimentally and theoretically, in a wide range of ionic combase characteristics of the solid could improve the extended DLVO positions of the dispersion medium, taking into account the results. q 1996 Academic Press, Inc. interfacial properties of the particles and the different inter