HSPiP, Computational Modeling, and QbD-Assisted Optimized Method Validation of 5-Fluorouracil for Transdermal Products.

Autor: Hussain A; Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Ramzan M; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India., Altamimi MA; Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Khuroo T; Department of Pharmaceutics, PGx Global Foundation, 5600 S, Willow Dr Houston, Houston, Texas 77035, United States., Mohd Siddique MU; Department of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule 424001, Maharashtra, India., Alnemer OA; Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2023 Dec 22; Vol. 9 (1), pp. 903-916. Date of Electronic Publication: 2023 Dec 22 (Print Publication: 2024).
DOI: 10.1021/acsomega.3c07061
Abstrakt: This study addressed the simplest and most efficient HPLC (high-performance liquid chromatography) method for the estimation of 5-fluorouracil (5-FU) from rat blood plasma by implementing the Hansen solubility parameters (HSP), computation prediction program, and QbD (quality by design) tool. The mobile phase selection was based on the HSP predictions and experimental data. The Taguchi model identified seven variables (preoptimization) to screen two factors (mobile phase ratio as A and column temperature as B) at three levels as input parameters in "CCD (central composite design)" optimization (retention time as Y 1 and peak area as Y 2 ). The stability study (freeze-thaw cycle and short- and long-term stability) was conducted in the rat plasma. Results showed that HSPiP-based HSP values and computational model-based predictions were well simulated with the experimental solubility data. Acetonitrile (ACN) was relatively suitable over methanol as evidenced by the experimental solubility value, HSP predicted parameters (δ h of 5-FU - δ h of ACN = 8.3-8.3 = 0 as high interactive solvent whereas δ h of 5-FU - δ h of methanol = 8.3-21.7 = -13.4), and instrumental conditions. CCD-based dependent variables ( Y 1 and Y 2 ) exhibited the best fit of the model as evidenced by a high value of combined desirability (0.978). The most robust method was adopted at A = 96:4 and B = 40 °C to get earlier Y 1 and high Y 2 as evidenced by high desirability ( D ) = 0.978 (quadratic model with p < 0.0023). The estimated values of LLOD and LLOQ were found to be 0.11 and 0.36 μg/mL, respectively with an accuracy range of 94.4-98.7%. Thus, the adopted method was the most robust, reliable, and reproducible methodology for pharmacokinetic parameters after the transdermal application of formulations in the rat.
Competing Interests: The authors declare no competing financial interest.
(© 2023 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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