Brief Analysis on Preformulations

If a new drug (chemical) structure is discovered, it is considered a huge breakthrough. This drug will need to be reconstructed into an appropriate formulation to produce the needed reaction at a particular site. Once the new molecule is seeded, the preformulation phase is started. Preformulation studies are defined as group study that deals with the new drug’s chemical, analytical, physical, and pharmaceutical properties. It also provides an overview of modifications that would be suitable for the drug so that its performance is enhanced. These studies will ensure the modification of drugs in such a way as to be effective, safe, stable and relatable pharmaceutical formulations. Preformulation studies utilise the knowledge from various fields such as toxicology, biochemistry, analytical chemistry and medicinal chemistry. 

Preformulation definition in industrial pharmacy

The preformulation definition in industrial pharmacy is its exploratory stage where the Physico-chemical characteristics of the new drug are characterised either by excipients or alone. It can also be described as a phase of research and studies along with development where the scientist characterises the physical, analytical, chemical, and mechanical properties of a new drug entity. The important properties among these that help in the formulation of a drug are drug solubility, dissolution rate, polymorphic forms, partition coefficient, and stability. Preformulation is the process by which a safe, reliable, and effective dosage form is produced.  

Preformulation objectives

• To produce an elegant, stable and effective form of dosage by developing a kinetic rate profile
• To check the compatibility of the new drug entity with various other ingredients 
• To develop a physio-chemical parameter of the new drug entity
• To produce useful data about how to design a drug delivery system with bioavailability
• To produce data that could be useful in producing a safe dosage form that can be manufactured in the market 

Preformulation studies – aim 

• To determine all the Physico-chemical characteristics of the new drug 
• To establish the kinetic rate profile of the drug 
• To generate the compatibility of the new drug with basic excipients

Classification of preformulation studies 

There are two prime classes of preformulation studies. They are:

1. Fundamental preformulation studies

These studies are related specifically to the drug molecules. It includes tests for solubility analysis (partition coefficient, solubilisation, thermal effect, dissolution, ionisation constant, etc.), stability analysis (solid-state and solution-state stability), and permeability analysis. All these studies/research depends on the chemical structure of the drug entity. 

1. Derived preformulation studies 

All the characterisation of particles is included in these studies. The particle properties (like size and shape of the particle), powder flow property, compaction behaviour, and bulk density are studied here. These studies are carried out on the dosage form.

Parameters in preformulation studies 

Chemical properties

Many chemical properties of the drug are determined in preformulation. Here, we will focus on hydrolysis, photolysis, and oxidation.

• Hydrolysis: This process involves the reaction of a drug molecule with water. This results in the cleavage of the chemical bonds in the drug molecule. If the drug molecule contains an ester or an amide functional group, then this reaction will happen at a faster rate. It will form carboxylic acid or alcohol.
• Oxidation: Most of the molecules will undergo oxidative degradation in the presence of atmospheric oxygen or auto-oxidation by the free radicals. Sometimes, oxidation can be initiated with the light of increased temperatures. Hence, the degree of oxidation can be controlled by exposing or avoiding light and high temperatures.
• Photolysis: It is a process in which the molecule undergoes decomposition by absorbing energy from light. As studied from oxidation, light also initiates oxidation along with photodegradation. If the drug molecule absorbs short wavelengths of light, then it undergoes oxidation. Various ranges of spectral regions are used to study the properties of drug molecules.

Physical properties

The physical properties that will be elucidated here are solubility, particle size, and flow properties.

• Solubility of the drug: It is only the most famous technique used during the preformulation of drugs. The solubility profile is known as the backbone for the study of preformulation. This stage determines the performance of the developed drug. The basis of biopharmaceutics classification is formed by solubility and permeability. 
• Particle size: Properties like dissolution rate, solubility, bioavailability, etc. all depend on the size of the particle. The particle size is applied in the following ways. 

1. To improve or enhance the solubility of the drug, the particle size must be reduced. 
2. Particle size determines the stability and quality of the pharmaceutical formulation in suspensions. 

The methods used to determine the particle size of the drug molecule are – microscopy, sedimentation rate, coulter counter method, etc.

• Flow properties: Frictional force, surface tension force, electric forces, and van der Waals forces are a few factors that flow properties depend on. 

For effective tablet formulation, the flow of drug entity powder is necessary. The flow property is more when the drug dose load is more. For hygroscopic materials, the flow property reduces the presence of absorbed moisture but increases cohesiveness.

Conclusion

In this article, we studied the preformulation definition. It is described as an exploratory stage where the Physico-chemical characteristics of the new drug are characterised either by excipients or alone. Preformulation studies are defined as group study that deals with the chemical, analytical, physical, and pharmaceutical properties of the new drug. The objectives of preformulation are to produce an elegant, stable, and effective form of dosage by developing a kinetic rate profile, to check the compatibility of the new drug entity with various other ingredients, and to develop a physio-chemical parameter of the new drug entity. Fundamental and derived are the two classifications of preformulation studies. The article elucidates the physical and chemical parameters evaluated in the preformulation studies.