Quality by Design Development of a Thermosensitive in situ Gel for Enhanced Ocular Delivery of Carvedilol

Introduction: This research focuses on formulating a thermoresponsive in situ gel containing Carvedilol for ocular delivery, employing a Quality by Design (QbD) strategy to improve therapeutic effectiveness in glaucoma management. Carvedilol, known for its β- and α1-blocking effects along with antioxidant activity, holds potential in reducing Intraocular Pressure (IOP) and protecting retinal cells. However, its therapeutic performance is hindered by poor retention and low bioavailability when delivered via standard eye drops. Objectives: To overcome these limitations, a sol-to-gel system was developed, which respond to ocular temperature and improve drug residence time. Materials and Methods: A 3² factorial design was implemented to assess the influence of polymer concentrations like Pluronic F127 and Pluronic F68 on key formulation parameters such as viscosity and gelation temperature. Results: The optimized formulation displayed ideal pH (6.8±0.2), high drug content (97.82±0.4%), and immediate gel formation at eye temperature. In vitro studies showed a controlled drug release profile of 97.62% over 8 hr, consistent with Higuchi kinetics. Safety evaluations including Draize and HET CAM tests confirmed the formulation's non-irritant behavior. Stability assessment under ICH Q1A(R2) guidelines indicated the formulation remained stable for at least 30 days. Conclusion: The developed in situ gel offers a promising, patient-friendly approach to glaucoma treatment by enhancing its ocular delivery.