**2. Optimization of an active molecular entity**

Following the successful pharmacological screening of an active molecular entity, one has to be sure about the appropriate molecular form of active molecular entity. The optimization of molecule is needed with respect to stability of molecule under normal environmental condition or with respect to enhancing the

**5**

*Preformulation Studies: An Integral Part of Formulation Design*

solvates, polymorphs, and more importantly prodrug.

This improvement can be made in area such as follows:

• Better organoleptic properties (taste masking)

• Modified release dosage forms

formulation that is to be developed.

than corresponding free acidic form.

current occurrence of hypertension.

salt forms.

strictly prohibited.

• Performance (increased solubility and bioavailability)

• Improved stability (hydrolytic and thermal stability)

• Increased patient compliance (decreased side effects)

performance of that molecule like bioavailability and stability. To inbuilt these virtues into a molecule, efforts are made to optimize a molecule inform of salts,

Nearly half of the drug molecules that are marketed as drug products are administered in salt form. Converting a molecule into a salt form is perhaps the most widely used approach to significantly enhance the performance of a molecule.

There are several factors that are needed to be considered while selecting appropriate salt form. The main factor that determines the appropriate salt form is type of

• Mostly, sodium and hydrochloride are the most suitable forms to be used if formulation to be developed is tablet, oral solution, or injectable. With sodium and hydrochloride as salt form, there is always enhanced solubility and hence better bioavailability is assured. For example, the propionic acid derivative naproxen exists in free acid form and has lower water solubility and hence less bioavailability. When it is converted to sodium salt, its water solubility is increased by severalfold and hence better bioavailability is assured. Similarly, tolbutamide, an oral hypoglycemic agent has 1000-fold greater water solubility

• Another factor that determines the type of salt form is type of formulation to be developed. For example, when the formulation to be developed is suspension, insoluble salt forms like tosylate, estylate, and embonate are the preferred

• Therapeutic indication is another factor that affects the selection of salt form. For example, if drug is indicated in the treatment of hypertension, the use of sodium or potassium salt is avoided. This is the main reason behind development of potassium salt of diclofenac, which is preferred over sodium salt. Diclofenac potassium can be given as analgesic in patient with history or

• As the regulatory perspective, selection of salt form must meet regulatory requirements and must be free from toxicity. For example, use of lithium salt is

• For immediate release formulations, generally sodium or hydrochloride salts are preferred as they show better solubility. For delayed release formulation, one can prefer low solubility salt form such as tosylate, estylate, and embonate.

*DOI: http://dx.doi.org/10.5772/intechopen.82868*

**2.1 Salts**

performance of that molecule like bioavailability and stability. To inbuilt these virtues into a molecule, efforts are made to optimize a molecule inform of salts, solvates, polymorphs, and more importantly prodrug.
