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Physicochemical is a fusion of two words, “Physico” and “Chemical”, which means physical and chemical. Hence, Physicochemical properties are all the physical and chemical properties of a drug. Both of these properties invoke the pharmacological response on the receptor, which can be a biological molecule or system with which it interacts.
Drugs interact with receptors to form the Drug Receptor Complex, which is responsible for the pharmacological actions of the drug. These diversified physicochemical properties of the drug administer the various pharmacological effects of the drugs.
Physicochemical Properties
The solute drug molecules have a spatial arrangement that defines their physical properties. They have some chemical composition that has some biological or chemical effects on the receptors.
Below are the physicochemical properties of drugs:
Isosterism
- Isosteres are compounds that have an identical number of atoms and molecules. Example N₂ and CO, N₂O and CO₂, etc. This phenomenon is called Isosterism.
Bioisosterism
- The isosteres that reflect the same kind of biological activities are called biological isosteres, and the physicochemical property is called bioisosterism.
- Bioisosterism controls the size, pKa value (strength of the acid), conformation, hydrogen bond formation, solubility, stability, reactivity, and hydrophobicity.
- When bioisosterism is implemented, it improves stability, reduces toxicity, lessens side effects, and improves the drug’s pharmacokinetics.
- Example- -COOH (Carboxylic acid) is replaced with – CH2N4 Tetrazoles to improve lipophilicity.
Hydrogen Bonding
- Hydrogen Bonding occurs between two atoms of different electronegativities like oxygen and hydrogen, fluorine and hydrogen, nitrogen and hydrogen. This difference in electronegativity can have an electrostatic attraction called a hydrogen bond.
Hydrogen Bonding can be of two types-
- Intermolecular – occurs between two molecules. Example- HF, H₂O.
- Intramolecular- occurs within the same molecule- C₇H₆O₃ (Salicylic Acid).
Hydrogen Bonding governs the water solubility, boiling point and melting point, drug-receptor interactions, the strength of the acid and biological products, spectroscopic properties, surface tensions, and viscosity critical in analysing the physicochemical properties.
Chelation (Complexation)
- The drug molecules need to cross through the lipid membranes, but complex molecules fail, which fails the pharmacological effectivity of the drug.
- Complexation reduces the absorption rate; hence diffusion slows down.
- For example- tetracycline with Calcium(milk) forms a complex, decreasing the diffusion rate of tetracycline.
Surface Activity
- The surface tension determines the absorption rate of the drug. Lower concentration surfactants reduce the surface tension, which increases the rate of absorption of the drugs. This is dependent on chemical structure, effect on biological membrane, concentration, and micelle formation of the surfactant. Hence affecting the physicochemical property of the drug.
Protein Binding
- The attachment of the protein to any non-specific or non-functional site without reflection of any biological activity is termed protein binding. The blood protein which frequently participates in the protein binding is albumin.
Solubility
- The amount of solute that dissolves in a solvent in equilibrium is called solubility at a given temperature. Solubility is dependent on the pH of the solute, temperature, and pressure. Solubility is essential because this measurement is required to prepare a liquid dosage of drugs. The interaction of the drug is possible only if the drug is in the solution phase before the absorption.
- The solubility of a compound can be improved by complexation, usage of cosolvents, use of surfactants, or structural modifications.
Partition Coefficient
- It is the concentration ratio of a compound in two different media immiscible in equilibrium. This factor is responsible for the distribution or spreading of drugs from the application area to the site of action through the lipid membranes of the cell.
- The coefficient is determined by the structure of the drug and the functional groups attached to the drug, which might be hydrophilic or lipophilic.
- Example: Phenobarbitone has a lipid/water partition coefficient of 5.9.
Dissociation Constant
- The dissociation constant is the measurement of the propensity of a larger compound to split into smaller components. This value is used to understand and estimate the chemical behaviour of the drug molecule. This is used to determine the deprotonation of atoms and molecules and protein-ligand binding. These factors govern the physicochemical properties of drugs.
Ionisation
- It is the acquisition of negative or positive charges by an atom or molecules by gaining or losing electrons and chemical changes. This is dependent on the pKa value and pH of the drug. Ionisation plays a vital role in the physicochemical property of solubility of the drug, which helps in drug-receptor interaction.
Redox potential
- Redox, also known as the oxidation-reduction potential, is the quantitative expression that defines the capability of a compound that has to gain or lose electrons.
- Redox potential is considered one of the most important physicochemical properties, especially in the case of vitamin preparation, as it determines the action of the drug.
- Redox potential can be calculated using the equation: E = E₀ + 0.0592/n log[conc. of reductant/conc. of oxidant]
Stereochemistry
- This branch of chemistry deals with the spatial arrangement of atoms and molecules of a compound and their positional impacts on the physicochemical properties. The isomeric compounds and any change in their structure can impact the physicochemical activity of the drug.
- Stereochemistry has a significant contribution to drugs used in psychiatric medicines. These drugs use enantiomers. Hence, one enantiomer may be more effective in one perspective, like biological, while another targets the therapeutic effects or pharmacokinetics.
- Example- (S) α-methyldopa is hypersensitive, whereas (R) α-methyldopa is inactive.
Conclusion
The physicochemical properties of drugs depend upon various factors like pH, temperature, pressure, and receptors iterating. These factors help in the measurements of constants like partition coefficients, dissociation constants, pKa value, etc., which constitute the chemical properties like micelle formation, redox potential, and complexation that forms the chemical part of the physicochemical properties of the drug. Others like stereochemistry and isosteric take care of the physical properties of the drug. Hence, the physical and chemical components combine to form the physicochemical properties of drug molecules or compounds.
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