Crystallization In The Pharmaceutical Industry

The importance of crystals to the pharmaceutical industry is evident that major of the pharmaceutical products contain a drug in crystalline form. Over 90% of all pharmaceutical products, such as tablets, aerosols, capsules, suspensions, and suppositories contain a drug in crystalline form [1]. Crystallization, particularly crystallization from solution, is the bottom-up unit operation in the production of pharmaceutical solids and is invariably used as a separation and purification procedure. The physical, chemical and structural properties of a compound are determined only when it is crystallized. Even a minor change in the crystallization process can change the crystal and powder properties of the material. Crystallization has been identified

Nevertheless, the significance of crystallization processes has been underestimated in the pharmaceutical industry. Overall, unfavourable and inadequately understood physical properties are often at the root of many of the problems that delay new drug approvals by regulatory agencies; and manufacturing issues, stock-outs and product recalls are costly consequences of poor control over material properties [6,7]. Therefore the crystallization process is regarded with prime importance in drug formulation and design. This concept is being increasingly recognised by the pharmaceutical industry and driven under new regulatory directives encouraging quality by design [8-11]. Crystallization at the molecular level is a supramolecular process [12]. In this context, the properties of the solid state are dependent on molecular recognition [13]. Thus understanding of the physical and intellectual property of the substance in solid form is very much necessary in designing the drug. In depth knowledge of crystallization process and solid-state properties of the Active Pharmaceutical Ingredient (APIs) clearly ensures the consistent dosage forms and implements in the drug delivery design

The rate of super saturation determines how and when crystals will form and for this reason a keen attention has to be followed in the supersaturation process. Supersaturation is defined as the ratio of the solution concentration (c) to the equilibrium concentration at a given temperature (c*). In an under saturated system nucleation and crystal growth are impossible, and crystal dissolution is most probable to occur [15, 17]. For the crystallization to occur, the system must be brought into a non-equilibrium state where the concentration of the solute exceeds its equilibrium concentration (i.e., the solution is supersaturated). Therefore the degree of supersaturation is the driving force for crystallization. Supersaturation in a solution can be induced by temperature change, solvent evaporation, chemical reaction, pH change, and alteration in solvent composition. The region bound by the solubility curve and the metastable limit (dashed lines) is termed as metastable