Basic Principle and Methodology of Molecular Distillation : Pharmaguideline

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Basic Principle and Methodology of Molecular Distillation

Thermally unstable compound and gaseous molecules with high boiling point and low volatility can be separated and purified with molecular distillation

Molecular Distillation


Thermally unstable compounds and gaseous molecules with high boiling points and low volatility can be separated and purified with molecular distillation, which is considered the safest method. The molecular evaporator is distinguished by its short residence time in the heat-exposed zone and the low operating temperature due to vacuum in the distillation space. As molecular distillation separates molecules based on their differences in mean free paths, molecules are separated. The molecules should be allowed to pass freely without colliding.


A simple molecular distillation involves placing a unit on a hot surface. As you can see in the following figure, the distillate travels only a very short distance before condensing. Substances with little viscosity dribble off the condensing surface of glass and flow to a receiving point. The liquid will be distilled on a heated surface near the condenser using a sophisticated apparatus that uses a different design. Film movement prevents non-volatile material from building up on the surface of a material to be distilled since a build-up could halt the distillation.

Centrifugal Molecular Distillation

In the food, pharmaceutical, petroleum, and chemical industries, this method of purification is employed under molecular distillation. In general, the unit is powered by low pressure and has a short residence time. The next stage involves degassing the feed material before it is pumped into a spinning disc that is pre-heated. Due to the expansion of the material on the spinning, preheated disk, the distillation process can be completed within milliseconds. Upon condensing at the outermost extremities of the shell, the distillate slowly flows into the collecting vessel.

Figure below shows that after spinning the disc, residual matter collects in the gutter surrounding it and is eventually collected in the collecting vessel below. The molecular distillation process takes place at very low temperatures, which means thermal decomposition cannot occur. A high vacuum prevents oxidation due to its exposure to atmospheric air. The pressure of molten salt distillation is 10-3 Torr, while the pressure of free-path distillation is very low, about 10-2 Torr.

Molecular distillation occurs at low pressure when the distance between the hot and condensing surfaces is smaller than the mean free path between them. There are several units in a series that are each one-stage. High molecular weight materials that are thermally sensitive can be processed by molecular distillation.

Film thickness is between 0.05 and 0.1 mm. The possibility of air ingress is very high in vacuum operations, while vapor emissions are likely to occur in pressure operations. Due to the presence of flammables in reboilers, column internals and adjacent piping, the distillation process is innately dangerous with flammables. This gradient has an effect on safety because it influences the concentration gradient between the top and bottom of the column. Impurities may be present in high concentrations in the column, posing a potential hazard.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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