1. Crystallization* Definition :Crystallization is the process of formation of solid crystals precipitating from asolution, melt or rarely deposited directly from a gas . Crystallization is also achemical solid–liquid separation technique, in which mass transfer of a solute fromthe liquid solution to a pure solid .*Importance of crystallization :1- purification of drugs .2- improve bioavalability of the drug and choose the most stable form.3- a crystalline powder is easily handled ,stable , possesses good flow properties and anattractive appearance .* Application of crystallization :Crystallization is a key component of almost all processes in the manufacturing ofsmall molecule pharmaceuticals. it is essential in both processing andpharmaceutical development. Since the properties of a solid material (polymorphism) can dramatically affect theprocess or the product’s compliance and effect (dissolution rate forexample), monitoring and controlling the isolation of solids for the variousapplications through crystallization is of paramount interest.so crystallization used in : 1- purification of drug 2- better processing characteristics 3- ease for handling 4- improved physical stability 5- sustained realese 6- improved bioavailability 7- preparation of organic and inorganic API 8- separation of API from galenical extracts 9- manufacturing of pure API by high yield
2. * Theory of crystallization :The three major stages in the process of Crystallization are-1. Super saturation of the solution : It can be done by three ways.Heating the solutionCooling the solutionSalting out2.Nucleation : This takes place in several steps.During their random motion, the atoms/ molecules/ ions will come closer to oneanother and forms aggregates called as CLUSTERS.These clusters will combine to form an EMBRYO. In this stage only the latticeformation begins. This embryo’s combine to form NUCLEI.From nuclei crystals are formed3.Crystal Growth : Once the crystals are formed, nuclei formation stops andcrystal growth begins.
3. *Crystallization crystallizers :Draft tube baffle technology:This type of crystallization is especially designed for lowviscosity products when a narrow crystal size distributionis expected.Super saturated product enters into a chamber containingthe massecuite (mixture of solids and solution).Instantaneously, the product crystallizes around thecrystals that are already inside the vessel so that thesolution reaches the saturation point. Inside the chamber, astirrer creates a high circulation flow in order to give agood repartition of the crystals in the massecuite.On the side of the vessel, baffles create a quiet zone wherean upward flow brings the smallest crystals out of thevessels. They are re-melted and put back in the vessel.Forced circulation crystallization:The design of such a crystallization unit is very similarto a forced circulation evaporator. A vertical tubularheat exchanger is only preferred due to the highviscosity of the massecuite.This type of crystallization unit is designed for thecrystallization of salts out of effluent.