Preformulation studies occur while examining a drug substance’s physical and chemical properties, individually and in combination with additional excipients.
It is defined as, “The process of optimizing a drug through the determination of those physical and chemical properties which are considered important in the formulation of safe, effective and stable dosage forms.”
Preformulation testing is the initial measure in the rational expansion of dosage forms of a drug substance. By analyzing the physical and chemical factors of the drug, the dosage of development is prepared.
The most basic preformulation studies‘ objectives are establishing a drug molecule’s physicochemical parameters that determine their desirability. The dynamic rate profile of drug substances affects drug stability (drug degradation, loss of activity).
To verify the congeniality of any drug with formulation excipients for likely communications. Lastly, establishing an adequate and durable storage form with better therapeutic values.
The preformulation studies take place in various steps. Mentioned below:
1) The process begins with selecting a drug and which doses have to be used for final drug development. The physical format of the drug is evaluated to discern its suitability of the drug against these factors.
2) A detailed study is conducted to determine physical properties.
3) Subsequently, the drugs are examined microscopically, such as density, particle size, shape, and crystalline form.
4) Later, they determine the drug’s chemical properties, like hydration, polymorphism, solvation, and so on.
5) They also determine whether the drugs are soluble, can be ionized, partition coefficient, and dissolution.
6) After this, the drug is tested for being kinetic and stable.
7) The drugs are now formed into different doses to evaluate their biological activity.
8) If the biological activity is deficient, then the entire process is repeated till they receive desirable outcomes.
9) But if the biological testing is a victory, then the drug’s ability is assessed with other doses from additives or excipients. Excipients and doses are chemical portions added to a drug.
10) Lastly, if the process is a triumph, the steps are noted and used for drugs’ industrial composition.
The parameters considered in the physical assessment are:
1) Macroscopic observations
2) Microscopic observations
3) Study of particle size and shape
4) Studies of partition coefficient and pKa
8) Physical form (crystal/amorphous)
9) Drug flow properties (density, porosity, angle of repose.)
The physical form is the first considered factor. They concern themselves with its structure; whether it’s amorphous or crystalline. The melting points, solubility, density, vapor pressure, and compressibility will vary depending on its structure.
These differences occur because the arrangement of molecules in the amorphous and crystalline format is different. Their energy value also differs for this reason.
The molecules are arranged in a fixed three-dimensional structure in the crystal form, which possesses more stability. The molecules are ambiguously arranged in an amorphous form and lack structure; hence, they are less stable and more soluble.
The crystalline form can impact the properties of the drug. It can affect the stability and syringe ability of the drug. This means that the ability to transfer through different capillaries is impacted.
WHAT IMPACTS PREFORMULATION?
1) Polymorphism occurs when the arrangement of molecules differs according to the temperature.
2) The size of particles and size distribution impact dissolution, drug absorption rate, taste, texture, color, and stability.
3) Partition coefficient impacts the absorption capacity of a drug through a biological site.
4) pKa, also known as the drug dissociation constant, throws light on the ionization properties of drugs and their physiological condition.
5) The solubility of a drug also influences the absorption rate and bioavailability.
6) Hydrolysis is the chemical breakdown of a drug, due to its response to water.
7) Oxidation is a drug degradation reaction that transpires in the presence of oxygen and its reactivity with drug molecules.
Preformulation studies provide a great insight into drug molecules and the subsequent formulation of a physiochemically stable and biopharmaceutical suitable dosage firm. The method encourages yielding an efficacious foundation to make drugs.
It is a proactive phase that pertains to transform new chemical substances into a further protected, effective, and crucially stable pharmaceutical formulation. Although a general report must be formed, highlighting the troubled areas that need reworking. This will aid in expanding successful drugs. After comprehensive satisfaction on all levels, an NDA is submitted. After its approval, the production commenc