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This paper presents a novel and computationally efficient numerical method for solving systems of fractional-order differential equations using orthogonal hybrid functions (HFs). The proposed HFs are constructed by combining piecewise constant orthogonal sample-and-hold functions with piecewise linear orthogonal right-handed triangular functions, resulting in a flexible and accurate approximation basis. A central innovation of the method is the derivation of generalized one-shot operational matrices that approximate the Riemann–Liouville fractional integral, enabling direct integration of differential operators of arbitrary order. These matrices act as unified integrators for both integer and non-integer orders, enhancing the method’s applicability and scalability. A rigorous convergence analysis is provided, establishing theoretical guarantees for the accuracy of the numerical solution. The effectiveness and robustness of the approach are demonstrated through several benchmark problems, including fractional-order models related to smoking dynamics, lung cancer progression, and Hepatitis B infection. Comparative results highlight the method’s superior performance in terms of accuracy, numerical stability, and computational efficiency when applied to complex, nonlinear, and high-dimensional fractional-order systems. Full article

Although fractional calculus has evolved significantly since its origin in the 1695 correspondence between Leibniz and L’Hôpital, the numerical treatment of multi-order fractional differential equations remains a challenge. Existing methods are often either computationally expensive or reliant on complex operational frameworks that hinder their broader applicability. In the present study, a novel numerical algorithm is proposed based on orthogonal hybrid functions (HFs), which were constructed as linear combinations of piecewise constant sample-and-hold functions and piecewise linear triangular functions. These functions, belonging to the class of degree-1 orthogonal polynomials, were employed to obtain the numerical solution of multi-order fractional differential equations defined in the Caputo sense. A generalized one-shot operational matrix was derived to explicitly express the Riemann–Liouville fractional integral of HFs in terms of the HFs themselves. This allowed the original multi-order fractional differential equation to be transformed directly into a system of algebraic equations, thereby simplifying the solution process. The developed algorithm was then applied to a range of benchmark problems, including both linear and nonlinear multi-order FDEs with constant and variable coefficients. Numerical comparisons with well-established methods in the literature revealed that the proposed approach not only achieved higher accuracy but also significantly reduced computational effort, demonstrating its potential as a reliable and efficient numerical tool for fractional-order modeling. Full article