In Silico Replication and Stoichiometric Sweet Spot Optimization of the Curcumin-Piperine Synergy: Validating The Hygieia Platform v2.1 Against Landmark Human Pharmacokinetic Trials

Deterministic in silico replication of the landmark human clinical trial by Shoba et al. (1998) evaluating curcumin bioavailability enhancement by piperine under ASME V&V 40 verification. In an adult European male reference physiology (73 kg), co-administration of 20 mg piperine with 2,000 mg curcumin increased free plasma Cmax by 26.1-fold (+2,510%), replicating the clinical 20-fold enhancement. Algorithmic Stoichiometric Sweet Spot exploration demonstrates that Shoba's 2,000 mg dose is an excessive megadose: the global Chou-Talalay synergistic optimum occurs at 1,000 mg Curcumin + 20 mg Piperine (CI = 0.178, Peak Synergism), achieving DRI = 2.00, conserving 365 g of active curcumin annually per patient while relieving hepatic Phase II glucuronidation saturation.