Sudhakar Kothaplly1, Shankar Alukapally1, Nagaraju Nagula1, Rambabu Maddela2. 1. ClinSync Clinical Research Pvt. Ltd., JSR Mall, Plot No. 7 to 18, Survey # 225, Opposite Mythri Nagar, Madinaguda, Hyderabad, Telangana, 500 050, India. 2. ClinSync Clinical Research Pvt. Ltd., JSR Mall, Plot No. 7 to 18, Survey # 225, Opposite Mythri Nagar, Madinaguda, Hyderabad, Telangana, 500 050, India. rambabu.m@clinsynccro.com.
Abstract
BACKGROUND: Despite its broad range of biological activities, use of curcumin is limited because of poor bioavailability. Here we report a novel curcumin formulation, Curcuwin Ultra+ (CU+), with superior bioavailability as compared to 95% turmeric extract (TUR 1800). METHODS: A randomized, double-blind, three-treatment, crossover oral bioavailability study was conducted in 24 healthy volunteers under fasting conditions. Subjects received a single dose of CU+ 250 mg, 500 mg and 1900 mg of TUR1800 as per randomization schedule and blood samples were collected at 4 h and 0 h before dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post dose. Total curcuminoids were measured as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and tetrahydrocurcumin using a validated LC-MS/MS method. RESULTS: CU+ achieved a significantly higher (p < 0.05) maximum plasma concentration (Cmax) and total systemic exposure (AUC0-6 and AUC0-12) for total curcuminoids as compared to TUR 1800. We observed 101 and 100 times higher Cmax respectively for 250 and 500 mg doses of CU+ as compared to 1900 mg of TUR1800. Similarly, AUC0-6 was 144 and 149 times higher whereas AUC0-12 was 99 and 113 times higher respectively for 250 and 500 mg doses of CU+ as compared to 1900 mg dose of TUR1800. Further, CU+ showed 40% faster absorption (p < 0.05). No safety issues were observed. CONCLUSION: CU+, which is designed for increased absorption and protection of curcuminoids from intestinal degradation, demonstrated superior bioavailability as compared to TUR1800 at considerably smaller doses. Additional clinical studies will help to demonstrate the impact of its increased bioavailability on efficacy. CLINICAL TRIAL REGISTRATION: CTRI/2020/10/028508 (Clinical Trials Registry-India).
BACKGROUND: Despite its broad range of biological activities, use of curcumin is limited because of poor bioavailability. Here we report a novel curcumin formulation, Curcuwin Ultra+ (CU+), with superior bioavailability as compared to 95% turmeric extract (TUR 1800). METHODS: A randomized, double-blind, three-treatment, crossover oral bioavailability study was conducted in 24 healthy volunteers under fasting conditions. Subjects received a single dose of CU+ 250 mg, 500 mg and 1900 mg of TUR1800 as per randomization schedule and blood samples were collected at 4 h and 0 h before dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post dose. Total curcuminoids were measured as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and tetrahydrocurcumin using a validated LC-MS/MS method. RESULTS: CU+ achieved a significantly higher (p < 0.05) maximum plasma concentration (Cmax) and total systemic exposure (AUC0-6 and AUC0-12) for total curcuminoids as compared to TUR 1800. We observed 101 and 100 times higher Cmax respectively for 250 and 500 mg doses of CU+ as compared to 1900 mg of TUR1800. Similarly, AUC0-6 was 144 and 149 times higher whereas AUC0-12 was 99 and 113 times higher respectively for 250 and 500 mg doses of CU+ as compared to 1900 mg dose of TUR1800. Further, CU+ showed 40% faster absorption (p < 0.05). No safety issues were observed. CONCLUSION: CU+, which is designed for increased absorption and protection of curcuminoids from intestinal degradation, demonstrated superior bioavailability as compared to TUR1800 at considerably smaller doses. Additional clinical studies will help to demonstrate the impact of its increased bioavailability on efficacy. CLINICAL TRIAL REGISTRATION: CTRI/2020/10/028508 (Clinical Trials Registry-India).