Finding Strategies for Controlling the Size of Paracetamol CrystalsIntroductionCrystallization Crystallization kinetics is the process of nucleation and crystal growth. For a crystal to be formed it has to undergo nucleation then growth to the desired levels (Jancic & Grootscholten 1984). Crystallization is the formation of an ordered structure from a solution or a melt (disordered structure phase). It is a representation of the mix between growth and nucleation. Crystallization is made possible by cooling down a semi crystalline polymer at specific temperatures or by adding solutions that reduce solubility and enhance crystallization.
It begins from a discrete point, the nuclei, and progresses to spherulite formed from growth of the crystal around the nuclei. The process of crystallization is complete when all the spherulites meet other neighbouring spherulites (Brahmia 2006) Crystallization kinetics consists of primary nucleation and secondary nucleation just as has been noted. Primary nucleation involves a number fluctuation of particles formed at a nucleus size formed at high super saturations (cooling surfaces/boiling zones/ where generation of super saturation exceeds dissipation of super saturation). Secondary nucleation is a number fluctuation of a band of particles generated as a result of the presence of a parent crystal (Jancic & Grootscholten 1984).
Formation of pharmaceutical compounds is mostly done by crystallization especially through cooling. Cooling crystallization ensures high yield and high purity of the products and can also be controlled to give a correct physical form of a product that dries and filters easily (Parsons et al 2003). Crystallization of paracetamol has two important principles which are nucleation and growth. The initial step in crystallization of paracetamol in ethanol is dissolution of the solvent and the solute at a specific temperature (60°c).
This first solvent is saturated at 55°c then kept at 60°c for complete dissolution. The next step is cooling below the solubility level which is 50°c with an addition of a 1 gram crystal. The temperature is held constant then cooling done by a non-linear cooling ramp. After the cooling step, the temperature cycling step follows then addition of an anti-solvent. Water acts as anti-solvent in paracetamol crystallization and is added to decrease solubility hence crystallize paracetamol. The temperature and total mass profiles in the reactor are plotted.
The program used for plotting such kind of data has to be selected (Worlitschek & De Buhr 2005). The crystallization kinetics and crystal population events determine the development of a population of crystals, in a vessel/reactor. Crystallization equipments assist in formation of desired crystals. They therefore have to be designed and operated in an efficient manner. For this to be done, the principles that control crystal formation have to be considered which are nucleation and crystal growth. Reactors Used in CrystallizationSeveral reactors are used in crystallization and there are four types of reactors.
These include; semi batch reactor, mixed flow reactor, batch reactor and plug flow reactor. Examples of reactors include automated lab reactors such as Auto Lab TM from Hertfordshire UK, LabMax R from Mettler-Tolledo, an Advantage Series TM from Argonaut Technologies in Red wood City, CA (Ekaterini & Andreas 2006). In an experiment on paracetamol crystallization, a semi-batch reactor known as HEL semi-batch reactor was used.