Conditions of Precipitation

In pharmaceuticals, precipitation is used as a method of purification to isolate pure crystalline pharmaceutical intermediate, ingredient, or excipient after bioprocesses. This purification process is performed to extract a pure form of the crystalline compound after the synthesis and extraction process.

In chemistry, solid formation in a particular solution comprises precipitation due to a chemical reaction. This precipitate formation is either due to reaction with solution or supersaturation by a compound. Due to chemical change in solution precipitation formation takes place.

Simple solution chemistry is the base of all precipitation processes. Condition for the formation of precipitation involves supersaturation by solvent change, the addition of soluble salts, etc. Due to supersaturation, excess solid precipitate in the solution.

This is due to nucleation which leads to the initial crystal formation of the solid precipitate. The condition for the formation of precipitation, methods and factors affecting the crystallisation process is discussed here.

So, let’s start with the topic.

CONCEPT OF PRECIPITATION 

Here we are going to see what the general concept of precipitation is.

In pharmacology crystal engineering of pharmaceuticals is responsible for controlling precipitation. Because it mainly controls the morphology of crystals, size distribution of a particular crystal as well as polymorphism.

The precipitation process depends upon the crystallisation of solids. Supersaturation is the condition for the formation of precipitation which is responsible to force crystallisation. The purity of crystals depends upon supersaturation level.

In solution the ratio between the concentration of the actual solution and saturated solution denotes supersaturation. It determines nucleation as well as the rate at which crystal formation takes place. The initial crystal formation process is known as nucleation.

This process directly affects the distribution of crystals according to their size. Nucleation gives rise to agglomeration which forms small crystals that further agglomerate with each other. This agglomeration depends upon the interaction between solvent and particle as well as particle-particle interaction.

As nucleation as it is inversely proportional to crystal size, final particle number mainly depends on it. Supersaturation is inversely proportional to the residence time. To obtain a particular sized crystal proper growth control on the crystal is important. The super suspension level at primary nucleation is responsible to obtain a crystal with a particular characteristic.

Therefore, control of supersaturation level is important. This can be achieved by controlling the supersaturation rate which further depends upon the rate at which the crystal grows and the available surface area of the crystal.

PRECIPITATION METHODS 

1. Reactive crystallisation

In the reactive crystallisation precipitation process the addition of precipitant chemical solubility of crystalline compounds decreases. This is the purification process that occurs after extraction.

A + B                             C + D

Where,

A, and B act as reactant molecules

C is the precipitate

D is the solute with high solubility

The precipitate form after reactive crystallisation may be in the hydrated form, solvate form, or insoluble solute.

Factors affecting the reactive crystallisation precipitation process include reaction kinetics vs. crystallisation kinetics.

Example: In the pharmaceutical industry addition of acid or base leads to a change in pH that comprises precipitate formation by reactive crystallisation.

2. Addition of percipient chemicals

This precipitation process mostly occurs in semi-batch mode as the addition of more than one chemical and subsequent continuous pumping in the reactor is required for mixing. For exothermic or endothermic reactions, temperature is the important parameter that is monitored during the process.

There are different factors of solutions that affect the precipitation process such as:

1. Precipitant and reactant selection

2. Solvent selection

3. Types of additives such as stabilisers, modifiers of habit

4. Concentration of reactant and precipitate.

There are different conditions followed during operation such as:

1. Resident time

2. Types of the impeller, intensity of mixing, distribution of concentration, and temperature in crystallise.

3. Feeding ratio reactant/precipitant -It comprises flow rate of mass, feed tube size, and hydrodynamic conditions at the feeding point.

Example: Due to the addition of inorganic salt into protein solution, salting out of protein takes place. This chemical reaction leads to precipitation by salting out proteins in the solution.

Nature of precipitation 

The condition for the formation of precipitation decides the physical characteristics of the precipitate. For example:

1. When the reactant is mixed at a high temperature near its boiling point heavy and granular crystals are produced.

2. The concentrated solution produces larger precipitate particles as compared to basic solutions.

Recovery of precipitation 

Methods involved in the recovery process of precipitate are:

1. Filtration

2. Centrifugation

3. Decantation

Applications

1.     To obtain fine particles of solid substances,

2.     Purification of solid after extraction

3.     To perform qualitative inorganic analysis

4.     To prepare salt during qualitative analysis reactions

5.     To make pigments

6.  To remove salts from water. 

Conclusion

The condition for the formation of precipitation involves a supersaturation level that quickly gives rise to nucleation. This step gives rise to the crystallisation precipitation process and forms precipitation in solution

In pharmaceuticals, this process is used to obtain pure crystalline solid product after extraction which is mainly involved in the purification process.

Furthermore to know about what are general concept of precipitation relation between supersaturation nucleation agglomeration discussed above.