Physicochemical Properties Of Drug
in this blog we are discussing about What are the different physicochemical properties of drug
What are the different physicochemical properties of drug absorption?
In which we know the "role" of some physical and chemical properties in our body in their biological action.
Physico + Chemical - Physical + Chemical
The various physico-chemical properties of drug molecules are,
1. Ionization: It is a process by which an atom molecules acquire a negative or positive change by gaining or losing electrons.
The resulting changed atom / molecules called an ion.
* Relation to biological action:
Rate of ionization in biological action (activity) in humans (animal)
- It play an important role in pharmacokinetics
- Pharmacokinetics involves ADME (Absorption, Distribution, Metabolism and Excretion)
- A Good balance of "ionized-unionized" form is better for pharmacokinetics.
- ionized form important good water solubility to the drug. which is essential for good binding interaction of dug with its receptor.
- While unionized form helps the drug to cross cell membrane. eg. The drug must be weakly acidic or weakly basic.
- the degree of dissociation (ionization) can be calculated using Henderson hassalbalch equation.
pH = pKa + log (unionized)/(ionized) - for base
eg. Acetic acid CH3COOH ( CH3COO+ [conjugate base]), (H+ [conjugate base])
2. Solubility: The maximum amount of solute particles which can be dissolved in per 100ml / gm of solvent is called the "solubility of the drug" at given temperature.
- It depends on the "nature" of solute and solvent as well as "temperature", "pH" & pressure (Hydrophilic & Lipophilic).
- The atoms and molecules of all organic substance are held together by various type of " bonds' (eg. Hydrogen bond, dipole-dipole, ionic bond etc.).
- Alter the structure of molecules.
- Use of co-solvents (ethanol etc.).
- Addition of surfactants.
- Complexation.
- Bioavailability of drugs mainly depends on their solubility in the given solvent system.
- Drug (solute) must be in "solution' before it can absorbed by biological membrane and some its activity.
- Drugs must be in solution to interact with receptors.
K = Co/Cw; solute A [Lipophilic (organic)]/ B [Hydrophilic (water)]
Where,
K = Partition coefficient.
Co = Concentration of drug in lipophilic (organic phase).
Cw = Concentration of drug in hydrophilic (aqueous phase).
*Important (Relation to biological activity).
- It affect drug absorption and distribution.
- It is generally used in combination with the pKa to predict the "distribution of drug" in biological system.
- since, biological membrane are "lipophilic" in nature. So the rate of drug transfer is directly related to the "lipophilicity of the molecules'.
- Helps to know the nature of drug that is hydrophilic or lipophilic (bioavailability).
K > L; Then drug is lipophilic.
K < L; Then drug is hydrophilic.
eg. Barbitol; (K) = 0.7
Phenobarbitol; (K) = 4.8
4. Hydrogen Bonding: The hydrogen bond is a special dipole-dipole interaction between the hydrogen atom in a polar bond such as N-H, O-H or H-F and electronegative atom O,N, F atom.
When any higher atom this hydrogen become electron deficient and they make a weak attraction and is called "Hydrogen bonding" and it is represented by the dotted line
It is two type;
a. Intermolecular bond.
when H-bonding is formed between two or more molecules. this gives association of molecules and forms dimers, trimers etc.
b. Intramolecular bond.
When H-bonding is formed between two atoms within a molecules. this result in formation of ring (chelation),
* Importance:- (Relation to biological action).
- Many physical properties are affected by hydrogen bonding.
- Intramolecular H-bonding generally melting point, boiling point, and solubility.
- Intermolecular H-bonding generally increase melting point, boiling point and solubility.
- It is very important in drug receptor interaction as well as their biological activity.
- It will also increase the water solubility.
It is the process in which drug molecules bind with protein, it form a complex type molecules and this phenomena is known as protein binding
After the absorption of drug, when drug reaches into systemic circulation it bind with the plasma protein which is already present blood and form a "plasma protein drug complex".
some proteins which present in blood;
- Albumin (Mostly attached).
- α-acid glycoprotein.
- Lipoprotein.
- Globulins.
a. Reversible complex: In this the , drug is bind with protein with very weak attraction forces like Vandarwalls forces and hydrogen bonding, so they can easily detache and drug become free and then this drug bind with receptor and give its pharmacological action.
b. Irreversible complex: In this, the drug bind with the protein with strong bond like covalent bond, so they can not detached. so, drug do not become free and it does not bind with receptor and not give pharmacological action.
*Important (Relation to biological action):
- It influence the bioavailability and distribution of active compounds (drugs).
- Both (complex & free drug) form are important for complete pharmacological action.
This is a one from of complexation . it is a type of bonding of ions / molecules to metal ion.
- A substance containing two or more ligand (which has lone pair) (donor) group may combine with a metal ion to form a complex known as chelates and the process is known as chelation.
* Importance (relation to biological action).
- when metals like lead, mercury, ion and arsenic build up in our body, they can be toxic, chelation there by used to treats this.
- In this EDTA is injected into the blood stream then this bind with heavy metals & make a chelates and then remove metal / minerals from the body.
- Used in poisoning.
In this medicinal chemistry Bioisosteres are group of chemical substituents which have similar physical or chemical properties with similar biological activity.
eg. CO2 & N2O , CO & N2 etc. fried man proposed a definition of Bioisosterism the phenomena by which compound usually fit with similar functional group (isosteres) and possess the same type of biological activity.
[Replacement may increase biological activity or sometime decrease biological activity].
* Types of Bioisosterism:-
1. Classical: they have similar shape and configuration of atom [valence electron same].
2. Non-classical Bioisosteres: they do not have same steric or electron configuration, but they have same properties due to this they give similar biological properties.
*Importance (Relation to biological action):
- Bioisosterism are broadly used to pharmaceutical sciences.
- It is used to reduced toxicity, change bioavailability.
- In drug design, the purpose of exchanging one bioisosteres for another is to enhance the desired biological or physical properties without change in their structure.
- Help in production of drug ( safe & more effective).
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