**3.3 Chirality**

*Pharmaceutical Formulation Design - Recent Practices*

Log P = (

• Chromatographic method (HPLC)

• Countercurrent/filter probe method

contains polar head and nonpolar tail.

• Computation based on software

which are as follows:

• Shake flask method

**3.2 Dissociation constant**

absorption and delivery. Due to lipidic nature of biological membrane, the amount of drug absorbed depends heavily on its lipophilicity. It is the unionized form of molecule that has better lipophilicity and hence it has received so much importance.

\_\_\_\_\_\_ Coil

If the value of Log P is 0, it indicated that drug has equal distribution in water and partition solvent. Value of Log P less than 1 is indicative of higher water solubility and value greater than 1 is indicative of higher lipidic solubility. For optimum solubility and absorption, a proper hydrophilic-lipophilic balance is necessary.

Determination of Log P value in biological system is next to impossible task, so several methods are available to determine partition coefficient of molecule in vitro,

Highly used method is shake flask method that utilizes octanol-water system to determine drug's partitioning behaviors. There are several reasons behind selection

• Octanol is believed to mimic the lipoidal character of biological membrane as it

• Octanol is organic compound that is immiscible with water; however, some of

Like partition coefficient, dissociation constant (pKa) is the property that determines the solubility in pH-dependent environment and extent of ionization. It is the extent of ionization that determines the absorption as only unionized form can be absorbed and hence it becomes essential to determine the pKa value of molecule.

Weakly acidic drugs having pKa value around 4 are best absorbed from stomach as they are predominantly present in unionized form. Basic drugs having pKa value of around 8 are best absorbed from intestine as they are predominantly present in unionized form. % ionization can be determined by the following equation:

Most of the strong acids and strong bases are present in ionized form throughout GIT and hence poorly absorbed. But it is also true that most of the pharmaceutical entities are derivatives of weak acids and weak bases and hence absorption is not an issue.

<sup>1</sup> <sup>+</sup> <sup>10</sup>(pH−pKa)} <sup>×</sup> <sup>100</sup> (2)

• Solubility parameter for most of the drugs resembles with that of octanol.

of octanol as partitioning solvent, which can be explained as follows:

the water is expected to be present in polar head portion.

pKa value determination gives idea about site of absorption.

%Ionization <sup>=</sup> { <sup>10</sup>(pH−pKa) \_\_\_\_\_\_\_\_\_\_

Cwater)equilibrium (1)

**8**

One of the most silent chemical parameters that define the pharmacological activity is the type of isomer. Many molecular entities exist in racemic form, but only one form gives the desirable pharmacological activity. Other present isomer may be devoid of pharmacological activity or may exhibit deleterious side effects. Most of us are known to teratogenic tragedy of thalidomide. Thalidomide exists as racemic form. Racemates contain equal amount of enantiomer, which are known as either levorotatory (−) or dextrorotatory (+) based on its ability to rotate the plane of polarized light [6].

It was introduced as a sedative agent. The S-enantiomer of thalidomide was a teratogenic agent, while R-enantiomer was effective as a sedative agent. Lack of knowledge about chiral selectivity leads to disastrous consequence. In recent times, single enantiomer is dominating the market over the racemate form due to better pharmacological performance. Nowadays, racemic switching or chiral switching is used in which racemic mixtures are developed as single enantiomers. Several single enantiomers are preferred over racemic form (e.g., levofloxacin (ofloxacin), esomeprazole (omeprazole), escitalopram (citalopram), and desloratadine (loratadine)) [7].

Overview of the same is given in **Table 1**. For better clinical performance of the molecule, it has become necessity to study the chirality of the molecule. In most of the cases, it can be studied by optical rotatory dispersion and circular dichroism [8].
