**4.1 Solubility**

*Pharmaceutical Formulation Design - Recent Practices*

perhaps the most studied after oxidation.

hence used as long-acting local anesthetic.

of hydrogen peroxide to the solution of substance.

through, which is the main factor for photodegradation [9].

*3.4.1 Hydrolysis*

alcohol.

administration.

*3.4.2 Oxidation*

*3.4.3 Photolysis*

*3.4.4 Racemization*

The major mechanisms by which a molecule undergoes degradation are hydrolysis, oxidation, photolysis, and racemization. Out of these mechanisms, hydrolysis is

Hydrolysis involves reaction of a molecule with water resulting in cleavage of a chemical bond within the molecule. If readily hydrolyzable functional groups are available, then reaction proceeds even at faster rates, making the molecule ineffective. Molecules containing esters and amide functional groups are prone to hydrolysis and especially the ester derivatives, which may lead to formation of carboxylic acid or an

• Effectiveness of molecule therefore depends on hydrolytic stability of molecule. For example, lidocaine is amide derivative of procaine, which is ester derivative used as local anesthetic. As ester derivative is more readily hydrolyzed; its duration of action is short while amide derivative is more stable and

• Beta-lactam antibiotics are susceptible to hydrolysis and hence they are supplied as dry powder injection where they are reconstituted before intravenous

Many molecules can undergo oxidative degradation, which involves exposure of molecule to atmospheric oxygen or autoxidation by free radicals. However, in some cases, oxidation can be initiated in presence of light or elevated temperature. So degree of oxidation can be controlled by avoiding exposure to lights and storage at controlled temperatures. Even the extent of oxidation can be controlled by addition of antioxidants. The extent of oxidation for a given substance can be studied by passing oxygen through the solution of substance, or it can be achieved by addition

Photolysis refers to decomposition of a molecule by absorption of energy when

It is an event where optically active molecule becomes inactive without any change in molecular composition. Such study is of highest importance when racemic mixture

exposed to light. Exposure to light not only brings photodegradation but may trigger oxidation. It is absorption of shorter wavelength components that may bring oxidation than longer wavelength components. Prior knowledge of photochemical behavior can provide guidance regarding storage condition, packaging, and handling condition. In most of the cases, the photochemical behavior of molecule is studied in the range of different spectral regions that are 200–290, 290–320, 320–400, and 400–700 nm. For example, riboflavin and vitamin B12 are susceptible to photodegradation directly and oxidation induced by light. So to avoid the decomposition, the formulation containing vitamin B12 and riboflavin is stored in amber color vials. Amber color bottles do not allow the ultraviolet radiation to pass

**10**

One of the most widely studied techniques during preformulation analysis is solubility profile of drug candidate. It is the backbone study of preformulation stage that determines the performance of developed formulation. Solubility and permeability forms the scientific basis of biopharmaceutics classification system (BCS), which can provide framework for designing type of drug delivery system. **Table 2** provides basic idea about basic BCS classification and link between solubility, permeability, and type of targeted formulation.

The solubility of a drug is the amount of the drug that dissolves in a given solvent to produce a saturated solution at constant temperature and pressure. **Table 3** provides outline of different levels of solubility. For conversion of drug molecule into an effective oral formulation, it must have good aqueous solubility for better absorption. Solubility is not an independent parameter but it relies on several properties like crystal characteristics, temperature, pH, complexation, and molecular structure. There are several techniques, which are available to improve the solubility of drug candidate, which are as follows:

