Preformulation study; the term is frequently heard in a pharmaceutical industry. But, what is it exactly?
A Preformulation study is an investigation of the physical, chemical, and mechanical properties of a drug substance to develop a safe, effective, and stable dosage form. Thus, it forms an integral part of the drug development process.
Just like any research study is carried out to accomplish a particular goal, the main objective of Preformulation studies is to accomplish the following:
- To establish the physicochemical properties of the new drug substance
- To determine its kinetic profile and stability
- To determine its compatibility with inactive ingredients or excipients
- To know the methods of drug processing and storage
In order to accomplish these goals, certain Preformulation parameters of the drug substance are investigated. Let’s see what these parameters are:
1.Organoleptic properties of the drug
Organoleptic properties are the aspects that can be experienced through one’s senses like taste, smell, sight, and touch. Thus, it includes a recording of the colour, odour, and taste of the drug.
2.Bulk characters of the drug
Crystallinity and Polymorphism
Crystallinity refers to the outer appearance and internal structure of the drug molecule and can affect its physicochemical properties.
Polymorphism is the ability of a compound to crystallise in different shapes with different internal structure.
Hygroscopicity is the measure of the tendency to adsorb atmospheric moisture by the drug substance. It characterizes the drug stability with respect to the environmental humidity.
Fine particle characterization
The size of the drug particle can influence its dissolution rate, suspendability and other properties. Thus, it becomes important to classify the drug substances as coarse, moderately coarse, very coarse, fine, and very fine.
Powder flow properties
Since the majority of active pharmaceutical ingredients are delivered as powders, either as a pill or for dissolution, understanding and controlling the powder behaviour of drugs are extremely important.
Powder flow properties help you understand the ease with which the drug powder will flow under a set of specific conditions like humidity, pressure etc.
- Ionization constant- pKa is the measurement of the acidity of the compound. Its determination helps in understanding the solubility, protein binding, and permeability of the drug substance to characterize its properties like absorption, distribution, metabolism and excretion from the body.
- pH solubility profile helps to understand the influence of pH on drug solubility, stability, and absorption.
- Common ion effect (Ksp) determines the solubility of the drug substance when a soluble compound having a common ion with the drug is added to the test solution.
- Thermal effects help to evaluate the drug solubility with respect to the changes in the temperature of the solvent.
- Solubilization is the method of increasing the solubility of sparingly soluble drug substance by various techniques like adding a co-solvent, changing the pH and temperature, adding a surfactant, reducing the particle size etc.
- Partition co-efficient is the measurement of the drug lipophilicity or ability to cross a cell membrane.
- Dissolution is the process of resolving the drug substance into its individual components and characterizing their properties.
The stability of the drug is studied with respect to various factors like:
- Stability in toxicology formulations
- Solution stability
- pH-rate profile
- Solid state stability
- Bulk stability
Thus, by investigating the above parameters of a new drug molecule, scientists can formulate the drug substance into a stable, safe, and effective dosage form that can be easily taken by the patient to cure his illness.