Related Experiment Video
Updated: Aug 7, 2026
11:42
Synthesis of Monodisperse Cylindrical Nanoparticles via Crystallization-driven Self-assembly of Biodegradable Block Copolymers
Published on: June 20, 2019
Continuous Distillation for Drug Substance Manufacturing
Kimberly E Penzer1, Daniel G Gregory1, Justin T Turnage1
1Department of Chemical and Life Science Engineering, Virginia Commonwealth University, 601 West Main St., Richmond, VA, 23284, USA.
Pharmaceutical Research
|August 6, 2026
Summary
Continuous distillation, a key separation technique, was adapted for pharmaceutical manufacturing to remove excess tert-butylamine during drug production. This pilot-scale system enables efficient impurity removal in advanced drug substance manufacturing.
Area of Science:
- Chemical Engineering
- Pharmaceutical Manufacturing
- Process Chemistry
Background:
- Continuous distillation is a staple in the petrochemical industry but underutilized in pharmaceutical manufacturing.
- Advanced Manufacturing Technologies (AMT) are transforming drug substance production.
- Efficient impurity removal is critical for pharmaceutical quality and safety.
Purpose of the Study:
- To develop and pilot a continuous distillation system for in-line removal of tert-butylamine.
- To integrate this system into an AMT for continuous drug substance production.
- To demonstrate the feasibility of continuous distillation for pharmaceutical impurity control.
Main Methods:
- Process simulation using ASPEN+
- Analytical characterization via HPLC and GC-FID.
- Engineering design and prototyping of a pilot-scale distillation column.
Main Results:
- A 3-foot continuous distillation column with automated reflux control was engineered.
- The system was integrated into a continuous albuterol sulfate manufacturing process.
- Demonstrated efficient removal of tert-butylamine at a 3.0 mL/min flow rate, yielding ~1,800 doses/hour.
Conclusions:
- Continuous distillation is a viable strategy for impurity removal in advanced pharmaceutical manufacturing.
- The developed system is scalable to meet production demands.
- General criteria for implementing continuous in-line distillation systems are provided.
Related Concept Videos
01:29Downstream Processing
Downstream processing begins once fermentation is complete and involves a series of steps to recover and purify products such as acids, vitamins, antibiotics, or proteins.Cell HarvestingFor example, for intracellular protein-based products, the first step is harvesting the cells. This is typically achieved using centrifugation or filtration to separate the cells from the liquid phase.Cell Disruption for Intracellular ProductsIf the target product is intracellular, the harvested cells must be...
01:17In Vitro Drug Dissolution: Alternative Methods
Alternative drug dissolution methods include the rotating bottle, intrinsic dissolution test, peristalsis, and the Franz diffusion cell method. The rotating bottle method involves meticulously rotating tightly capped controlled-release beads in a temperature-controlled bath. Periodic decanting of samples allows for residue assay, followed by refilling with fresh medium and testing at various pH levels to emulate the gastrointestinal tract conditions.In contrast, the intrinsic dissolution test...
01:09In Vitro Drug Dissolution: Compendial Testing Models II
Various dissolution methods are utilized to assess a drug’s dissolution rate, including the flow-through cell, paddle-over-disk, cylinder, and reciprocating disk methods.The flow-through cell apparatus (USP (United States Pharmacopeia) method 4) comprises a reservoir for the dissolution medium and a pump that propels the medium through the cell containing the test sample. This method is crucial for assessing modified-release dosage forms with minimally soluble active ingredients, maintaining...
01:13In Vitro Drug Dissolution: Compendial Testing Models I
Compendial dissolution methods are standardized procedures defined by pharmacopeias to evaluate the rate at which a drug dissolves in a specific medium. These methods ensure batch-to-batch consistency, enable quality control, and support the prediction of drug bioavailability. They are critical for both immediate and modified-release drug products.The apparatuses used for dissolution testing differ in their design and mechanical function, but all aim to simulate the physiological environment of...
01:14Drug Dissolution: Requirements and Profile Comparison
The acceptance criteria for dissolution profile data are anchored in Q values, representing the percentage of drug dissolved within a specified period. This assessment unfolds in three stages:First Stage: The test passes if all six drug dosage units are equal to or greater than Q plus 5%; otherwise, the sample proceeds to the second stage.Second Stage: The average of twelve units must be equal to or greater than Q, with no unit falling below Q - 15% to pass; if not, it progresses to the final...
01:03Sublimation
Sublimation is the direct transformation of a solid to a gaseous state. For instance, at standard pressure and room temperature, solid carbon dioxide sublimes to gaseous carbon dioxide. The phase diagram depicts the conditions required for sublimation. This process occurs at the solid-gas phase boundary and is not observed above the triple point of the substance. The reverse of sublimation is called deposition, where a gaseous substance condenses directly into a solid. Sublimation and...