A greener pharmaceutical industry

Quality control

The production of Active Pharmaceutical Ingredients (APIs) is the critical stage for ensuring the quality and safety of medicines. Key factors in API production include controlling impurities, managing polymorphism (different crystal forms of the same molecule), and optimising particle size, each of which plays a significant role in the final product's performance and safety.  

Impurities

Impurities in APIs are unavoidable but must be controlled within specified limits to ensure product safety and efficacy. Advanced analytical techniques have significantly improved the impurity profiling of APIs, highlighting the importance of identifying, characterising, and quantifying impurities and degradation products in drug substances and pharmaceutical products (Khandale et al., 2023). These efforts aim to enhance drug therapy safety by identifying toxic impurities with selective procedures.  

Regulatory guidelines

The four key and comprehensive guides for assessing impurities in pharmaceutical products, including APIs, raw materials, and intermediates today, are the European Pharmacopeia (EP), guidelines from the European Medicines Agency (EMA), the United States Pharmacopeia (USP), and guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). These documents serve as the cornerstone for ensuring the quality and safety of pharmaceuticals by providing detailed standards and procedures for evaluating contaminants and impurities. 

Polymorphism

Polymorphism refers to the existence of an API in multiple crystalline forms, each with distinct physical and chemical properties affecting the drug's performance. Polymorphism control is crucial for maintaining the physicochemical and pharmacological properties of APIs while ensuring consistent quality in pharmaceutical production.

The characterisation of polymorphic forms is currently studied using various techniques, including X-ray diffraction, microscopy, thermal analysis (such as differential scanning calorimetry and thermal gravimetric analysis), and various forms of spectroscopy (e.g. IR, Raman, solid state NMR) (FDA, 2007).

For example, Rietveld et al. (2021) investigated the polymorphism of benzylthiouracil, a drug used to treat hyperthyroidism. This study focuses on the two crystalline forms (dimorphs) of benzylthiouracil, known as form I and form II. It provides a comprehensive analysis of the crystal structures, thermal properties, and stability of these forms using the aforementioned characterisation techniques. The study concludes that understanding the polymorphism of benzylthiouracil is crucial for its effective use in pharmaceutical formulations, ensuring the stability and efficacy of the drug. 

Particle size

Particle size could affect the dissolution rate, bioavailability, and stability of APIs. The technology used for measuring and controlling API particle size and morphology has advanced, enabling more precise formulations and better control over the physicochemical properties of pharmaceuticals.