Having spent a career in pharmaceutical development and more specifically pharmaceutical formulation it has always seemed strange to me that books on the subject of pharmaceutics do not lay more emphasis on formulation as a subject.
It is a fact that for any drug substance a medicine for administration to patients cannot exist without both a formulation and a process by which that formulation can be used to make the medicine. Hence, one of the aspects of early development of any new medicine looks at the formulation. A team of formulators is an important part of any development group and the question of how to formulate any potential candidate drug has to be considered at an early stage. For any medicine to be administered to a patient it needs to be in a form which the patient can take and in which it can reach the required target in the body effectively and safely. To devise a successful formulation the formulator has to gather information and take account of numerous factors that include the physical and chemical properties of the active ingredient in the medicine, its stability and its compatibility with other ingredients.
By way of a frequently encountered example, when considering formulating a solid oral dosage form there are several properties of an active ingredient which would be important to consider. These would include, but are not limited to, the bulk density and flow properties of the active ingredient as well as the particle size of the active ingredient. A low bulk density material has a large volume relative to its weight and there are negative implications from this when attempting to compress the material into a tablet using conventional tableting equipment. Related to low bulk density is poor powder flow. Poor flow refers to the low ability of a powder to flow in a desired manner and makes formulation difficult. In order to make a compressed dosage form the powder must flow into a die cavity on a tableting machine but materials with low bulk density typically do not flow well. At the same time, particle size is also important and can influence formulation method and techniques.
As part of a formulator's role decisions have to take account of preferred routes of administration and potential dosage forms. There are many possible routes including oral, parenteral, pulmonary and topical administration. Likewise there are numerous possible dosage forms available for drugs including tablets, capsules, granules powders and solutions. Decisions as to which route of administration and which dosage form is most suitable will depend on the properties of the active ingredient in the medicine, the disease to be treated and, potentially, the patient group which is to be treated; for example if the medicine is for the paediatric population an oral liquid is likely to be the required route and dosage form.
The intention of this book is mainly to emphasise the importance of formulation and the approach is essentially to focus on specific dosage forms such as tablets, capsules and liquids. Altogether eleven of the thirteen chapters have this focus. The starting point is a chapter on pre-formulation which is an essential need whatever dosage form is to be developed. The content of several of the chapters is applicable across a range of dosage forms; pre-formulation and excipients are examples. The need for modified release of the drug from the dosage form is also a commonly required feature of many products and separate chapters are included to cover the subject of coatings and controlled release. Other chapters concern the special needs of paediatric products and the different emphasis on how to formulate products acceptable to children and the elderly.
In addition to the main dosage forms there are others which are less commonly used although equally important when they are used. Some of these are included in a separate chapter on alternative dosage forms. A further special case concerns how the growing number of drugs emanating from biotechnology are formulated. Here the need for a different approach with different analytical techniques is essential and is covered in a separate chapter.
A unique inclusion is the chapter on intellectual property (IP). In this world where research-based companies operate side by side with generic companies it is not surprising that costs of development and pricing of products are key to economic success. The chapter on IP is intended to try to explain some of the issues and pressures of patents and other forms of protection which exist and how companies work through these complications. It is a fact of life that no company can afford to invest too much time and money into developing a product unless there is a reasonable chance of receiving an adequate return on their investment. Whether research-based or generic this has to be kept in mind. The IP status of the drug substance itself, its formulation and perhaps the process by which the product is made are all important factors in this regard; hence the inclusion of the chapter on IP in the book.
The final chapter is in some ways an over-arching chapter in which much of the content of the ‘dosage form’ chapters is seen to fit into a much larger picture of pharmaceutical development rather than the specifics of formulation. It is hoped that this chapter will add greatly to students' overall knowledge of the whole process of how new products are developed.
Another advantage of having worked in the area of formulation for a considerable time is that I have been able to get to know a large number of pharmaceutical scientists. I approached all of the authors to ask them to write chapters the subjects of which are within their own expertise and experience. All are world class in their fields and from your studies you may already recognise some of the names. I am confident in the quality of their writings. I am sincerely grateful to all of the authors for their commitment to contribute and particularly wish to acknowledge Dr Kendal Pitt for his advice and for helping me to keep the book on track. I am also grateful to the Royal Society of Chemistry for asking me to compile and edit the book and for the guidance of their editorial team.
I hope you will find the book a useful source of information whether you are pre-graduate, post-graduate, already working in the area of product development or just interested in pharmaceutical formulation and the development of medicines.