Solubility of solids in liquids:
Factors influencing solubility-
- Particle size (surface area) of drug particles ↓Particle size → ↑ surface area→ ↑Solubility.
Log S/So = 2ϒv/2.303RTr
So is the solubility of large particles
S is the solubility of fine particles
γ is the surface tension of the particles
V is molar volume
T is the absolute temperature
r is the radius of the fine particle
R is the gas constant
- Molecular size- Molecular size will affect the solubility. The larger the molecule or the higher its molecular weight the less soluble the substance. Larger molecules are more difficult to surround with solvent molecules in order to solvate the substance. In the case of organic compounds the amount of carbon branching will increase the solubility since more branching will reduce the size (or volume) of the molecule and make it easier to solvate the molecules with solvent.
- The boiling point of liquids and the melting point of solids: Both reflect the strengths of interactions between the molecules in the pure liquid or the solid state. In general, aqueous solubility decreases with increasing boiling point and melting point.
- The influence of substituents on the solubility of molecules in water can be due to their effect on the properties of the solid or liquid (for example, on its molecular cohesion, or to the effect of the substituent on its interaction with water molecules. Substituents can be classified as either hydrophobic or hydrophilic, depending on their polarity. Polar groups such as –OH capable of hydrogen bonding with water molecules impart high solubility. Non-polar groups such as –CH3 and –Cl are hydrophobic and impart low solubility. Ionization of the substituent increases solubility, e.g. –COOH and –NH2 are slightly hydrophilic whereas –COO– and –NH3 are very hydrophilic. The position of the substituent on the molecule can influence its effect on solubility, for example the aqueous solubilities of o-, m- and p- dihydroxybenzenes.
- Temperature will affect solubility. If the solution process absorbs energy then the solubility will be increased as the temperature is increased. If the solution process releases energy then the solubility will decrease with increasing temperature. Generally, an increase in the temperature of the solution increases the solubility of a solid solute. For all gases, solubility decreases as the temperature of the solution increases. A few solid solutes are less soluble in warm solutions.
- Crystal properties- Polymorphic Crystals, Solvates, Amorphous forms Solubility of solids in liquids. Polymorphs have the same chemical structure but different physical properties, such as solubility, density, hardness, and compression characteristics A drug that exists as an amorphous form (non crystalline form) generally dissolves more rapidly than the same drug in crystalline form.
- pH is one of the primary influences on the solubility of most drugs that contain ionizable groups. Solubility depends on the degree of ionization. Large number of drugs are weak acids or weak base. Degree of ionization depends on the pH Solubility of solids in liquids Factors influencing solubility About 85% of marketed drugs contain functional groups that are ionised to some extent at physiological pH (pH 1.5 – 8).
Multiple choice questions(MCQs)
1.Which of the following factors influence solubility?
d)all of the above
2.Solubility depends upon
d)all of above
3.Decrease in particle size _____ solubility
d)depends on the crystal structure
4.Log S/So = 2ϒv/2.303RTr. In this equation S is
a)solubility of large particles
b)solubility of fine particles
c)surface tension of the particles
5.The larger the molecule or the higher its molecular weight the ____ soluble the substance
6.Which option will be the best example of the physicochemical properties of drugs?
a)Solubility, particle size, polymorphism, salt form, pseudopolymorphism, complexation, wettability, pH, Pressure of disintegration
b)Pressure of disintegration, polymorphism, salt form, pseudopolymorphism, complexation, wettability, pH
c)Solubility, particle size, polymorphism, salt form
d)Solubility, particle size, polymorphism, salt form, pseudopolymorphism, complexation, wettability
7.In general, aqueous solubility ______ with increasing boiling point and melting point.
d)first increases then decreases
8.Which form of a drug has greater solubility?
9.Depending on their polarity substituents can be classified as
d)a) and b)
10.Larger the size of the counterion, greater the solubility.
11.If the solution process absorbs energy then the solubility will be ______ as the temperature is increased.
d)depends on the polarity of molecules
12.If the solution process releases energy then the solubility will ______ with increasing temperature.
d)first increase then decrease
13.In a saturated solution with endothermic dissolution, how does the concentration of dissolved solute change with increasing then decreasing temperature?
c)Increases and decreases
d)Decreases and increases
14.For all gases, solubility _____ as the temperature of the solution increases.
d)first increases then decreases
15.Which of the following dissolves more rapidly?
- d)all of the above
- d)all of above
- b)solubility of fine particles
- d)Solubility, particle size, polymorphism, salt form, pseudopolymorphism, complexation, wettability
- d)a) and b)
- d)Decreases and increases
- a)amorphous form
1. Martins Physical Pharmacy, 6th edition 2011, page no. 332-355.