Drug Formulation: A Science Or Not A Science?

What is drug formulation?

The definition of the drug (pharmaceutical) formulation states that it is the process in which different chemical substances and/or biochemical substances, such as active chemical substances will be combined together to produce a final medical compound i.e., medical drug . The term ‘formulation’ can however mean not only the inputs and process of manufacturing the drug, but include also the final product dosage form, which is what the patient eventually experiences and what at the same time should not discourage patients to stick to the drug dosage regimen . In practise, the discovery of a new drug is just the beginning of the following long procedure that has to be completed for a new medicine to be developed . Therefore, after the identification of a promising molecule, it is then passed to the formulation scientists. Their task is to find and work out how to create a final formulation that would be the best option for that drug, whether it is injection, a single-shot dose pill or a cream2. However, is it right to name the people that work on this process ‘scientists’?

„Learning before doing” – Preformulation studies

During the drug discovery and development, there are a large number of studies carried out. They involve, among others, pre-clinical in vitro laboratory safety tests, initial volunteer/patient studies and full-scale clinical trials (Fig.1.1 and Fig.1.2 ). For each of them the potential medical substance has to be formulated into an appropriate dosage form. The formulations of the drug, their nature and composition will vary among the stages of the development. However, the formulation prepared for the full-scale clinical trials must be the final one (the same as the product moved to marketing). Pre-formulation studies are conducted to make sure that there are optimal formulations chosen for the intended use, but also to evaluate the characteristics of the candidate drugs and the potential formulation excipients4, which are inactive substances that serve as the vehicle or medium for a drug or other active substance and their interaction with drug substances. Therefore, preformulation studies are essential to determine the appropriate formulation ingredients. An additional function of the preformulation studies is to test the influence of potential conditions of preparation, storage and manufacture on stability, to ensure that the assessment of a candidate drug has the essential reliability during development and post-marketing use. For this reason preformulation studies may be defined as laboratory studies to determine the characteristics of active substance and excipients that may influence formulation and process design and performance4.

What characteristics of a drug substance are assessed by the preformulation studies and why are they importantant?

Determining the Formulation

A science or not?

Once we understand what a drug formulation actually is, we can think if it can be classified as a science. However, initially it is essential to define the term science and to find out what it covers. The problem is that it is actually quite difficult to define science, since it applies to a very broad set of human endeavors, from for example developing lasers, to analyzing the factors that affect human cognitive processing . The word „science” comes from the Latin term scientia („knowledge”), meaning knowledge based on demonstrable and reproducible data (according to the Merriam-Webster Dictionary) . On the other hand, the Oxford Dictionary states that the English word science means „the intellectual and practical activity encompassing the systematic study of the structure and behaviour of the physical and natural world through observation and experiment” . There are some key features that join together these various activities from a large spectrum encompassed by science. Therefore, even though the boundaries of science are not clearly defined, if something does not meet most of the typical characteristics, it should not be treated as science9.

First, and probably one of the most important features is that a science focuses on the natural word. It studies and asks questions about the components of the physical universe like atoms, plants, ecosystems, human beings, but also the natural forces at work on those things. Therefore, science cannot study supernatural forces and explanations, because they are not classified as a part of the natural, physical world that we, as people directly see, investigate and experience9. To my mind, there is no doubt, that a drug formulation focuses on the natural world. While determining the right formulation, the chemical substances, their properties and interactions are investigated, which means that the process of drug formulation studies the chemical components of the physical universe around us to find the best way to combine them in order to form suitable, acceptable and efficient medical products. In addition, it is completely certain that drug formulation does not expect answers that are beyond the natural word, like the explanation based on supernatural forces.

All of these factors explained above support the view that drug formulation is a science. However, what may make us think that it is not? What are the other options that drug formulation can be considered to be? To my mind, the other possible option is to classify drug formulation as art, but only to a certain extent. In fact, determining the proper combination of ingredients, while balancing product quality, stability, cost, and many other factors can be sometimes considered a puzzle. Art can be defined as the expression of human creative skill and imagination, typically in a visual form such as a painting, producing works to be appreciated primarily for their beauty or emotional power . In my opinion, determining a suitable drug formulation reqiures a dose of creativity. This process is based on arranging and combining certain elements to form a final product and it is the researcher’s job to think of appropriate ingredients that can potentially possess the desired properties while combined with the active substance to form a final medical compound. Therefore, the drug formulation actually is an application of human creative skills. On the other hand, a characteristic of art is that it requires skills developed through experience which can be applied to drug formulation. The more experience a formurator has, the more able he is to come up with an idea of what excipients would be potentially suitable for a certain drug substance. However, although apparently there are some features that art and drug formulation have in common, it has nothing to do with creating something with the aim for it to be appreciated primarily for its beauty or emotional power. Therefore, drug formulation can be considered art but only to some extent. However, does it mean that it cannot be considered science anymore? Drug formulation may be both art and science. Both are interdependent and inseparable16. Different parts of the formulator scientists’ work require different skills, some of them are more related to science and others to art. The process on his own is science without a doubt, but would be impossible without the human beings that conduct it and their creativity and skills gaind through experience.

Final verdict

Drug formulation possesses all the essential scientific features, from the fact that it focuses on the natural world, through the use of testable ideas and evidence to repeatable observations. For this reason, it can be said with full confidence that it is a right and confirmed idea to call people working on this process „formulation scientists”. However, it is also important to bear in mind that these scientists are also human beings. Human beings that bring to the work their own creativity and skills, making a drug formulation an artistic process. These artistic features are not in opposition to the conclusion that drug formulation is a science, but are necessery in this process. In my opinion, it is therefore right to consider drug formulation a science, but it is also worth remebering a quote from Albert Einstein: „The most beautiful thing we can experience is the mysterious. It is the source of all true art and science. He to whom the emotion is a stranger, who can no longer pause to wonder and stand wrapped in awe, is as good as dead —his eyes are closed”.