Formulation and Evaluation of Carteolol Hydrochloride-Loaded Cubosomal pH-Sensitive In-Situ Gel for Glaucoma Therapy

Abstract

Background: Glaucoma is a chronic optic neuropathy that requires effective intraocular pressure control. However, the hydrophilic nature and rapid nasolacrimal drainage of conventional Carteolol HCl eye drops limit ocular bioavailability to less than 5%. This study developed a novel pH-sensitive in-situ gel loaded with Carteolol HCl cubosomes to enhance precorneal residence and sustain drug delivery. Method: Nine cubosomal formulations (F1–F9) were synthesized via melt dispersion-emulsification using glyceryl monooleate and Poloxamer 407. The optimized dispersion was incorporated into a pH-sensitive matrix composed of carbopol 934 and HPMC. The formulations were characterized by particle size, zeta potential, entrapment efficiency, and TEM. The evaluation included gelling capacity, in vitro release kinetics, and three-month stability studies. Results: The optimized formulation (F5) exhibited a particle size of 157.9 nm, high entrapment efficiency (85.73 ± 1.08%), and drug content of 91.46 ± 1.14%. TEM confirmed a spherical, bicontinuous cubic architecture. F5 was incorporated into Carbopol 934 and HPMC-based gels, in which the optimized IG2 formulation exhibited a rapid sol-to-gel transition (18 s) at physiological pH (7.4). IG2 provided controlled drug release (61.46 ± 2.¹²% over 12 h) via anomalous non-Fickian transport. Sterility and three-month stability studies confirmed safety and physical integrity of the formulation. Conclusion: The results suggest that the developed Carteolol HCl-loaded cubosomal in-situ gel formulation offers promising potential for improving ocular bioavailability and patient compliance in the long-term management of glaucoma.