Biopolymer Applications Journal
Volume 5, Numéro 2, Pages 30-37
2026-07-13

Process Simulation Of Vitamin C Syrup Manufacturing: An Aspen Plus®-based Approach For Pharmaceutical Unit Operations Optimization



Authors : Hammou Tewfik . Fatmi Sofiane . Lezrag Hayet Ahlem . Taouzinet Lamia . Benslimane Abdelhakim .

Abstract

The pharmaceutical industry increasingly relies on process simulation tools to optimize manufacturing workflows, reduce development costs, and ensure regulatory compliance. This study presents a comprehensive simulation of vitamin C (ascorbic acid) syrup preparation using Aspen Plus® V12.1, focusing on critical unit operations including mixing, dissolution, crystallization, and cross-flow membrane filtration. The process was modeled using the Non-Random Two-Liquid (NRTL) thermodynamic base property method, with crystallization/dissolution kinetics parameterized according to the McCabe growth law. Three sequential BatchOp unit operation under Batch Model (Batch Process), CRISTAL1–3 were employed to dissolve sucrose (933.4 kg), ascorbic acid (1.436 kg), and vanillin flavoring (0.1436 kg) in purified water (500 kg), achieving a final syrup composition of 65.0% w/w sucrose, 0.1% w/w vitamin C, and 0.01% w/w vanillin. The simulation demonstrated complete dissolution of all active and excipient components within 105 min for sucrose, 60 min for vitamin C, and 15 min for final homogenization, with cross-flow filtration (CFFilter modules) effectively removing insoluble impurities and non-sugar solids. The final product exhibited a standard liquid density of 1.3276 g/cm³, closely matching the European Pharmacopoeia specification of 1.32 g/cm³ at 20°C. This work establishes a validated digital twin framework for liquid pharmaceutical manufacturing, demonstrating how simulation-driven process design can enhance quality assurance, reduce material waste, and accelerate scale-up from laboratory to industrial production.

Keywords

Process simulation, Aspen Plus, Vitamin C syrup, Pharmaceutical unit operations, Crystallization/dissolution kinetics, Cross-flow filtration.

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