Dissolution is the process where a solute in gaseous, liquid, or solid phase dissolves in a solvent to form a solution.
Solubility is the maximum concentration of a solute that can dissolve in a solvent at a given temperature. At the maximum concentration of solute, the solution is said to be saturated. The units of solubility are often provided in mol/L or g/L.
Factors that affect solubility include:
The rate of dissolution is represented by the Noyes-Whitney equation: dm/dt = DA(Cs - C)/h
Effect of temperature on liquid and solid solutes
The solubility of a solid or liquid can increase or decrease as temperature increases depending on whether the dissolution reaction is exothermic or endothermic.
Increasing solubility with increasing temperature
In endothermic reactions, increasing temperature increases the solubility of the solute. This is because the net energy from bonds is breaking and forming means that heat energy is absorbed when the solute dissolves in solution.
Increasing temperature introduces heat into the system. So according to Le Chatelier’s Principle, the system will adjust to this increase in the heart by promoting the dissolution reaction to absorb some of the heat energy.
An example of a solute that increases in solubility with increasing temperature is ammonium nitrate which can be used in first-aid cold packs. As ammonium nitrate dissolving in solution is an endothermic reaction, heat energy is absorbed from the environment. This causes the surrounding environment to feel cold.
Decreasing solubility with increasing temperature
In exothermic reactions, increasing temperature decreases the solubility of the solute. This is because heat energy is released when the solute dissolves in solution. Increasing temperature introduces more heat into the system. So according to Le Chatelier’s Principle, the system will adjust to this excess in heat energy by inhibiting the dissolution reaction.
An example of a solute that decreases in solubility with increasing temperature is calcium hydroxide which can be used in medical situations to treat chemical burns and as an antacid.
Effect of temperature on gas solutes
A gas becomes less soluble as temperate increases. This is because in general heat energy is released as gas dissolves in solution i.e. the process is exothermic.
Increasing temperature (increased heat energy) results in increased kinetic energy. This increase in kinetic energy allows greater movement in the gas particles resulting in the intermolecular bonds between the gas solute and solvent being broken.
Pressure: Henry’s Law
The solubility of gas is affected by changes in pressure to the system. A gas dissolves in liquids to form solutions. This results in equilibrium in the system where a proportion of gas molecules is dissolved in liquid while a proportional remains in the gas above the liquid.
Henry’s law states that: “At constant temperature, the amount of gas that dissolves in a volume of liquid is proportional to the partial pressure of the gas in equilibrium with the liquid.”
C = kP
Hence as the pressure of the gas above the liquid in the system increases, the gas molecules become more soluble in the solvent. Likewise, if the pressure of the gas in the system decreases, gas becomes less soluble in the solvent.
Limitations of Henry’s Law on gas solubility:
Methods to enhance dissolution to improve oral bioavailability include:
Le Chatelier’s principle:
If stress (e.g., pressure and heat) is applied to equilibrium, the system will respond by adjusting to minimize the effects of this stress.
For example, if pressure is applied to a system, the dissolution reaction will respond to minimize this stress by reducing the pressure in the system.
Heat of solution
Solids and liquids are a result of individual particles held together by winter particulate bonds. To form a solution energy is required to break the bonds between the particles within the solid/liquid. Heat energy is also required to break the bonds in a solvent to insert one of the molecules into solution. Hence these processes are endothermic. Heat energy is released when the solute molecules form bonds with the solvent molecules i.e. this process is exothermic.
Depending on whether more energy is used to break the bonds within the solute and solvent or is released when new bonds are formed between the solute and solvent, the reaction overall can be exothermic or endothermic.
Total amount of heat energy released or absorbed from the system = sum of heat energy absorbed when bonds are broken – sum of heat energy released when bonds are formed
Example of Henry’s Law: Decompression Sickness
Henry’s Law explains the phenomena of decompression sickness. When scuba divers submerge themselves in deep water, the pressure in their body increases. This causes the nitrogen in their body to dissolve in their blood. Nitrogen is physiologically inert, so it is not used in tissue metabolism. If the scuba diver ascends to the surface too quickly, the sudden drop in pressure causes nitrogen bubbles to come out of solution and form painful and potentially fatal gas embolisms.
Dissolution is important for health practitioners because, for drugs to be absorbed and have a physiological effect in the human body, they must be in solution. For solid preparations, such as tablets and suppositories, the rate of dissolution affects how fast a drug is absorbed in the body.
Aqueous solubility is often considered when formulating drugs. Poorly soluble formulations provide difficulties in the development of pharmaceuticals. Chloramphenicol, phenytoin, and digoxin are some examples. Drugs, particularly those for oral administration, which have low aqueous solubility may have low bioavailability leading to insufficient exposure in the body causing the drug to be not as effective.
|Temperature and solvent effects in the solubility of some pharmaceutical compounds: Measurements and modeling., Mota FL,Carneiro AP,Queimada AJ,Pinho SP,Macedo EA,, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2009 Jun 28 [PubMed PMID: 19406228]|
|Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates., Blagden N,de Matas M,Gavan PT,York P,, Advanced drug delivery reviews, 2007 Jul 30 [PubMed PMID: 17597252]|
|Improving drug solubility for oral delivery using solid dispersions., Leuner C,Dressman J,, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2000 Jul [PubMed PMID: 10840192]|
|Determination of differential heat of solution in real solutions from variation in solubility with temperature., Hollenbeck RG,, Journal of pharmaceutical sciences, 1980 Oct [PubMed PMID: 7420303]|
|Medical problems associated with underwater diving., Melamed Y,Shupak A,Bitterman H,, The New England journal of medicine, 1992 Jan 2 [PubMed PMID: 1727063]|
|Emergency treatment of chemical and thermal eye burns., Kuckelkorn R,Schrage N,Keller G,Redbrake C,, Acta ophthalmologica Scandinavica, 2002 Feb [PubMed PMID: 11906296]|
|Toxic dermatitis caused by ammonium nitrate released by a cold pack., Ni C,Takahashi R,Levins P,, Contact dermatitis, 2016 Apr [PubMed PMID: 26948419]|