Basic Concepts and Requirements of Galenic Formulations

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3. Formulation Testing

The traits or properties of the active substance are evaluated for solubility, stability, particle size, and moisture absorption.

The physical, chemical, microbiological and analytical methodology is developed to test how stable the medicinal product is. Stability testing is done during formulation development. Its purpose is to retain the quality, safety and efficacy of the active substance and the medicinal product. Galenics experts are also responsible for the safe storage of a medicine. They ensure that the content of the active ingredient remains constant, and that the product is chemically stable and maintains its purity throughout its shelf life.

Stability testing helps scientists to understand the effect of temperature, humidity, and packaging. These three elements together determine the shelf-life for the medicinal product. The scientists also retest the period for the active substance, and the storage conditions to be applied to the label. Finally, they determine the primary packing requirements. This activity supports the use of the product in the clinic and for the regulatory submission.

Analytical scientists have more responsibilities. They work to understand the characteristics of the active substance and the medicinal product.  These include the physical properties of the product and its impurity profile. The scientists also produce data and reports to meet testing and regulatory requirements. The methods followed are:

  • Physical properties analysis, to understand the characteristics of the active substance and medicinal product.
  • High throughput stability analysis, to monitor potency.
  • Impurity analysis, to reduce and control related substances from side reactions, genotoxins and degradants, foreign matter or other process impurities.

When it comes to the physical properties of an active substance, the in vivo performance and manufacturability of a formulation are influenced by how the intermediates and the final product are processed. It is necessary to understand both the active substance and the formulation physical properties in order to submit and file a patent. Regulatory authorities are increasingly interested in this area. It is therefore essential to understand the unique physical properties of a medicine throughout its development life cycle.

The formulation and manufacturing processes which are developed to deliver medicinal products for early clinical trials are also important. They should be reliable and follow good manufacturing practice in the entire process, as well as in the scale-up, placebo and reformulation.

Once these factors are fully considered, the formulation can be produced on an industrial scale. It begins with a prototype, and the next step is to reproduce it on a laboratory scale. The scientists then need to transfer the validated analytical methods, formulation and manufacturing processes to processes in manufacturing facilities. The scientists finally reach large-scale production by scaling up the production in several steps at the test facility. The newly developed medicine formulation is initially used and tested in clinical trials (as so-called Investigational Medicinal Product (IMP)) before it can reach the patient as an approved medicine.