Modification of in situ gelling behavior of carbopol solutions by hydroxypropyl methylcellulose

Aqueous solutions of Carbopol [polyacrylic acid (PAA)] are low viscosity acidic solutions that transform into gels upon an increase in the pH and, therefore, may be used as in situ gelling ophthalmic drug delivery systems. However, the amount of PAA required in the solution to form stiff gels upon installation in the eye is not easily neutralized by the buffering action of tear fluid. A reduction in the PAA concentration without comprising the in situ gelling properties as well as the overall rheological behavior of the system can be achieved by adding a suitable viscosity-enhancing polymer. The rheological properties of aqueous solutions containing PAA and hydroxypropyl methylcellulose (HPMC), a viscosity-enhancing polymer, evaluated as a function of temperature and pH, were similar to those of pure PAA solutions; that is, both form low viscosity liquids at pH 4.0 and transform into stiff gels with plastic rheological behavior and comparable viscosities upon increasing the pH to 7.4. In addition, HPMC-PAA gels show slow in vitro release of incorporated timolol maleate. Thus, the HPMC-PAA combination demonstrates properties suitable for formulation as a liquid ophthalmic delivery systems, which upon instillation into the cul-de-sac of the eye can undergo in situ phase transition to form gels capable of sustained drug release.