PHC 222 Part(I) Dr. Huda Al Salem. Lecture (10). How to improve water solubility?. 1- Salt formation. 1- Salt formation. -Salt formation usually improves the water solubility of acidic and basic drugs as the salts of these drugs dissociate in water.
1- Salt formation
-Salt formation usually improves the water solubility of acidic and basic drugs as the salts of these drugs dissociate in water.
-The degree of water solubility depends on the structure of the acid or base used to form the salt
Many GIT disturbances can be treated by ingestion of water-soluble compounds.
Tartaric acid >>>>Na K tartrate is used as mild laxative
- Salt formation is also used to change the taste of drugs to make them more palatable to the patient
Chlorpromazine HClis water soluble but it has a very bitter taste. However, the water insoluble embonate salt is tasteless.. So it can be administered orally in the form of a suspension
2- Incorporation of water-solubilizing groups
a- Type of group introduced
b- Degree of permanency
c- The biological effect of the group
d- Methods of introduction
1- Incorporation of strongly polar alcohol, amine, amide, carboxylic acid, sulphonic acid and phosphorus oxyacid groups give analogues with water solubility higher than those formed by introduction of ether, aldehyde & ketonic functional groups.
2- Introduction of acidic and basic groups give a wide range for dosage forms that increase water solubility.
3- Zwitterions reduces water solubility.
4- Incorporation of weakly polar groups such as carboxylic acid esters, aryl halides & alkyl halides increases lipid solubility.
1- Groups that are bound directly to the carbon skeleton of the lead compound by C-C, C-O & C-N bonds are attached to by irreversible bonds.
2- Groups that are linked to the lead compound by ester, amide, phosphate & glycosidic links are more likely to be metabolized to reform the parent lead compound.
In order to preserve the type of activity exhibited by the lead, the introduced group should be attached to a part of the structure that is not involved in the drug-receptor interaction (Pharmacophore).
Some groups have certain biological activity..
1- acidic groups exhibit haemolytic properties.
2- aromatic acid groups exhibit anti-inflammatory activity
3- carboxylic acids with an alpha functional group exhibit chelation property.
4- Basic groups have a tendency to change the mode of action
1-Water-solubilising groups may be introduced at any stage in the synthesis of a drug.
2-Many methods involve the use of protecting groups.
3- Groups protected are either the water- solubilizing group or groups already present in the lead structure.
Acetal protection of a ketone during Reductionof an Ester.
1- COO- by acylation
Chloramphenicol sodium succinate is supplied as a lyophilized powder which is dissolved only in water when needed & not more than 48 hours
2- Sulphonic acid groups (-SO3H)
3- Basic groups
-By alkylation or acylation
-Amide derivatives are usually more stable than esters in aqueous solutions
4- Polyhydroxy groups
5- Ether groups
3- Formulation Methods
a second solvent added to the original solvent, in small concentrations, to form a mixture that dissolve the solute.
1- Minimal toxic effect
2- Should not affect stability of the drug
Paracetamol elixir in an aqueous solution
is dissolved by the use of mixture of
ethanol & 1,2-dihydroxypropane,
Prepared by dissolving a high concentration of the drug in an organic solvent that is miscible with water. Then, the concentrated solution is rapidly mixed with an aqueous solution containing a suitable stabilizer which adsorbed on the surface of the colloidal particles.
Ex: Shaving Cream (Foam) (g in L)
Mayonnaise (L in L)
Blood (S in L)