The Exploration and Use of Thermal Analytical Technologies During Formulation and Process Development of Freeze-Dried Products

The Exploration and Use of Thermal Analytical Technologies During Formulation and Process Development of Freeze-Dried Products
Winter 2003
Nathaniel Milton, Ph.D., Abira Pyne, Ph.D., Dinesh Mishra, Ph.D., and Lian Yu, Ph.D.
Eli Lilly and Company
APR
Abstract
Thermal analysis is widely used in the pharmaceutical industry to evaluate solution and solid-state systems. Differential scanning calorimetry is an especially valuable tool during formulation and process development of freeze-dried pharmaceuticals to understand the influence of thermal history on the physical state of excipients and the active pharmaceutical ingredient in frozen solution and freeze-dried powders. This review discusses applications of differential scanning calorimetry in characterizing process-induced transformations, which can significantly influence the physical and chemical characteristics of the freeze-dried powder. A case study is presented to illustrate how thermal analysis guides the formulation and process development of freeze-dried products.
Introduction
A broad objective in product development is the application of analytical tools to facilitate formulation and process definition. The physical characterization of frozen solution and freeze-dried powders is critical during the development of freeze-dried products. It is important to understand the physical state of the active pharmaceutical ingredient and the excipients in the frozen solution, the influence of thermal history and processing conditions on these solutes, and the influence of storage conditions on the physical and chemical stability of the dried product. A variety of tools such as freeze drying microscopy and thermogravimetric analysis (TGA) are often used as complimentary tools for characterization [1-3]. One of the most widely applied and useful thermal analytical tools is the Differential scanning calorimetry (DSC). The following is a review of the information provided by DSC and a case study illustrating how DSC is used in conjunction with other analytical tools during formulation development.
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