Quality by Design: Process Trajectory Development for a Dynamic Pharmaceutical Coprecipitation Process Based on an Integrated Real‐Time Process Monitoring Strategy

Authors

Huiquan Wu, Food and Drug Administration
Mansoor A. Khan, Texas A&M University Health Science Center

Date of this Version

2017

Document Type

Article

Citation

Comprehensive Quality by Design for Pharmaceutical Product Development and Manufacture, First Edition. Edited by Gintaras V. Reklaitis, Christine Seymour, and Salvador García-Munoz.

Comments

U.S. government work.

Abstract

Increasing prevalence of poorly water‐soluble drugs in pharmaceutical development provides notable risks of new products demonstrating low and erratic bioavailability. This dissolution‐limited bioavailability may have consequences for safety and efficacy, particularly for drugs delivered by the oral route of administration. Several novel drug delivery technologies have been developed to improve drug solubility, dissolution rates, and bioavailability. Among those are solid dispersion, nanotechnology, supercritical fluid technology, lipid‐based technology, and crystal engineering. Although these strategies are available for enhancing the bioavailability of drugs with low aqueous solubility, the success of these approaches is not yet guaranteed and is greatly dependent on the physical and chemical nature of the molecules being developed. On the other hand, crystal engineering [1] offers a number of routes such as cocrystallization [2, 3] and coprecipitation [4–6] to improve solubility and dissolution rate. Coprecipitation of poorly soluble drugs with polymers, an important technique for improving the dissolution and absorption of drugs, has been modified in recent years to prepare extended‐release preparations. Previous work on coprecipitation was largely focused on formulation development and product characterization [4–6], for example, optimization of process variables for the preparation of ibuprofen coprecipitates with Eudragit S100, screening of process and formulation variables for the preparation of extended‐release naproxen tablets with Eudragit L100‐55, and preparation and characterization of coprecipitate of ibuprofen using different acrylate polymers. It was not until recently that the process analytical technology (PAT) approach [7–11] was explored to gain insights about the coprecipitation process and process monitoring.