Development and In-vitro Optimization of Telmisartan-Curcumin Solid Dispersion Nanoparticles for the Management of Diabetic Nephropathy Using DoE Approach.

Objectives: This study aimed to develop and optimize Telmisartan-Curcumin Solid Dispersion Nanoparticles (SDNs) to improve the management of diabetic nephropathy by enhancing Telmisartan's solubility and release rate.

Methods: A Box-Behnken design was used to optimize the formulation with critical excipients PVP VA S630 and Poloxamer 407. Pre-formulation studies assessed Telmisartan's solubility and lipophilic nature. The optimized formulation (TLS-15) was evaluated for solubility, drug release, particle size, zeta potential, and in vitro release. A comparison was made with a formulation without Curcumin (TLS-15 WC). TEM imaging and release kinetics analysis were conducted.

Results: The optimized formulation (TLS-15) demonstrated significantly improved solubility (4.801 μg/ml) and drug release (99.68%) with an appropriate particle size (303.5 nm) and zeta potential (-12.17 mV). TLS-15 WC exhibited lower values for solubility (4.74 μg/ml), drug release (98.3%), particle size (291.2 nm), and zeta potential (-25.4 mV). TEM revealed uniformly distributed spherical nanoparticles. TLS-15 showed a 99.54% release after 6 hours, compared to 98.3% for TLS-15 WC, following first-order release kinetics (R = 0.9934).

Conclusions: The study successfully developed and optimized Telmisartan-Curcumin SDNs, enhancing Telmisartan's solubility and release. Curcumin played a critical role in boosting the therapeutic potential of the formulation. While challenges remain with stability and manufacturing, the formulation shows promise for improving bioavailability and efficacy in diabetic nephropathy treatment. However, additional studies are needed to validate its effectiveness.