The Development of API Manufacturing Processes – Targets and Strategies

Abstract

This article gives an overview on the questions to be asked and the activities to be planned during the development of an API manufacturing process. First of all the API properties required for formulation such as purity, polymorphism and solvate formation, residual solvents, particle morphology and particle size distribution have to be defined. Then process parameters have to be evaluated that ensure that the drug substance with these properties can be produced on lab scale. The transfer to large-scale production is discussed with emphasis on scale-up effects, appropriate equipment, potential bottlenecks, and cost aspects. Finally practical hints are given as how to design an API crystallization and work-up process in a way that all given requirements for the APi are fulfilled and the process can be run reproducibly and cost-effective in production.

Influence of Filtration on the Agglomeration Degree of Two Crystalline Amino Acids

“…The aim of this process is a product with well-defined properties concerning particle size, size distribution, flow and surface characteristics [2,3]. The aim of this process is a product with well-defined properties concerning particle size, size distribution, flow and surface characteristics [2,3].…”

Particle Engineering of an Active Pharmaceutical Ingredient for Improved Micromeritic Properties

“…Examples of molecules that can be crystallized in two-or three-dimensional habits (plates and blocks, respectively) from polar solvents are known in the literature [1,25,26]. In those examples, decreasing solvent polarity leads to crystallization of one-dimensional (needle-like) particles.…”

“…It is worth noting that seeding with dry material can be inefficient owing to possible surface amorphization occurring during processing of the solid as well as agglomeration during its storage [1]. However, disagglomeration and surface healing can be induced by preparing a slurry of crystals in the crystallization solvent.…”

“…Goodness-of-fit of a ln x = f(1/T) linear regression was used to evaluate the data accuracy and for interpolation purposes. Additionally, the derived enthalpy of fusion (ΔH fus ) 1) was compared with a value obtained from a differential scanning calorimetry (DSC) measurement.…”

“…Besides reducing impurities to the necessary level, a number of solid-state properties have to be achieved; the desired and registered stable solid form has to be crystallized reproducibly and the particle-size distribution (PSD) has to be in the desired range [1]. In addition, the crop has to have certain micromeritic properties such as bulk density, flowability, or wettability that determine the further processing of the active ingredient, i.e., its formulation (e.g., tableting) and performance (as dissolution rates or aerodynamic behavior) [2].…”