CO-CRYSTALLIZATION ENABLED CANDESARTAN CILEXETIL AND HYDRO-CHLOROTHIAZIDE TABLETS FOR IMPROVED BIO AVAILABILITY IN HYPERTENSION MANAGEMENT

Background: Hypertension often requires combination therapy for effective control. The combined use of candesartan cilexetil and hydrochlorothiazide is limited by poor water solubility and low oral bioavailability. Co-crystallization with suitable co-formers can improve solubility and dissolution, thereby enhancing therapeutic efficacy. Objective: This study aimed to create and assess an immediate-release (IR) tablet containing co-crystals of Candesartan cilexetil and Hydrochlorothiazide, utilizing urea as a co-former to improve solubility and dissolution rate, thus enhancing bioavailability. Methods: Co-crystals of Candesartan–Urea and HCTZ–Urea were synthesized using the solution evaporation technique. The resulting co-crystals were analyzed using FTIR, and PXRD to verify co-crystal formation and evaluate compatibility. The optimized co-crystal mixtures were compressed into immediate-release tablets with superdisintegrants. The formulations underwent evaluation for pre- and post-compression parameters, in-vitro dissolution, and stability under ICH conditions. Results: The optimized formulation displayed excellent flow characteristics and consistent weight distribution. The immediate-release tablet disintegrated rapidly and showed significantly improved dissolution compared to the pure drugs. The dissolution data adhered to Hixson–Crowell kinetics, indicating uniform drug release through surface erosion. FTIR and PXRD confirmed co-crystal formation without chemical interaction between the drug and excipients. Stability studies revealed no significant changes in drug content, hardness, friability, or release profile after 30 days. Conclusion: The developed Candesartan–HCTZ co-crystal immediate-release tablets showed improved solubility and dissolution with good physical and chemical stability, highlighting co-crystallization as an effective strategy to enhance the bioavailability of poorly soluble antihypertensive drugs.