Modelling Programmes for Industrial Scale Drug Production

Modelling Programmes for Industrial Scale Drug Production Different modelling programs of the production of a drug on an industrial scale Crystallisation: Crystallisation is usually used for the split-up, purification and the creation stage in the chemical industries. It is one of the oldest and most crucial unit operations. Crystallisation is a practical method of gaining a chemical substance that is concentrated. This concentrated chemical substance is in a form that is nice and simple to handle. There are various ways in which crystallisation could be carried out, such as melt, vapour and solution. However, recently melt has been the most popular one as there are great demands for it because of its good purification technique. Chemist always wants to get the chemicals they make as pure as possible and a good way of purifying chemicals is to make crystals of them. When they are in solution, you can have all sorts of impurities. But when they form crystals, the crystals the crystals contain much purer compounds than in the solutions. And the impurities are left in the solution. Generally, the crystals are a very precise arrangement of molecules all the same fitting together. The impurity has a different shape so it doesn’t fit in properly. Sometimes we get an impurity that is the wrong shape and we can get rid of it. Each time we recrystallise it e.g. make some solution, form crystals, filter them out, re-dissolve them, and form more crystals. Each time we crystallise it we get a purer and purer compound. Sometimes in the old days people crystallised thousands of times to get something really pure. The problem is that when you have a solution even if you want to cool it down which is the standard way of getting crystals to form. The crystals cannot form unless you get it something small for the first crystal to form around. Once the first one goes, the whole lot goes (Ssci-inc.com, 2014). There are three following steps in which the development of a certain crystal for the duration of crystallisation process follows. The three following steps that it continues over are; nucleation, crystal growth and Ostwald ripening. Embryos are created by the molecules of the substance combined, in the nucleation step. A macroscopic crystal can be created if the circumstances are for example if the embryo is allowed to reach a critical size known as nucleus. However, the embryo will dissolve if the circumstance is such that it is not possible to reach the critical nuclear size. Crystallising substance can exist in more than one crystalline phase for example; solvates or polymorphs. If that’s the case then each stage will have its own specific embryonic combined and nucleus. The differen t embryos in the supersaturated solution compete for solute molecules (Ssci-inc.com, 2014). The type of embryo that first reaches the critical nuclear size forms a nucleus for that particular crystalline phase and hence enables that phase to grow into macroscopic crystals. Because of the time that is involved in the competition for nucleation this step is controlled by kinetic considerations on condition that that the thermodynamic driving force for the formation of the crystallizing phase is favourable, i.e., ΔG is negative (Ssci-inc.com, 2014). Drug Design: Drug design is sometimes referred to as rational drug design. This is the inventive process of finding new medications based on the knowledge of a biological target. The drug is usually an organic small molecule that activates or inhibits the function of a biomolecule e.g. such as a protein, which in turn results in a therapeutic benefit to the patient. Drug design, in the most basic sense, involves the design of small molecules that are complementary in shape and charge to the bimolecular target with which they interact and therefore will bind to it. Drug design often but not essentially relies on computer modelling techniques. This type of modelling is often referred to as computer-aided drug design. Lastly, drug design that relies on the information of the three-dimensional structure of the bimolecular target is known as structure-based drug design. The phrase drug design is to some extent a contradiction, but what is really meant by drug design is ligand design (i.e., design of a small molecule that will bind tightly to its target). Although modelling techniques for prediction of binding affinity are reasonably effective, there are many other properties, e.g. such as bioavailability, lack of side effects, metabolic half-life, etc. That first must be optimized before a ligand can become a safe and efficient drug. These other characteristics are often difficult to optimize using rational drug design techniques (drug design, 2014). Typically a drug target is a key molecule involved in a particular metabolic or signalling pathway that is specific to a disease condition or pathology or to the infectivity or survival of a microbial pathogen. There are some methods that attempt to inhibit the functioning of the pathway in the diseased state by causing a key molecule to stop functioning. Drugs may be designed that bind to the active region and inhibit this main molecule. Another method may be to enhance the normal pathway by promoting specific molecules in the normal pathways that may have been affected in the diseased state. Also adding to that, these drugs should also be designed so as not to affect any other important off-target molecules or anti-targets that may be similar in appearance to the target molecule, since drug communications with off-target molecules may lead to undesirable side effects. Sequence homology is frequently used to identify such risks (drug design, 2014). Most frequently, drugs are organic small molecules produced through chemical mixture, but biopolymer-based drugs, also known as biologics, which is produced through biological processes, are becoming gradually more common. In addition, mRNA-based gene silencing technologies may have therapeutic applications (drug design, 2014). There are two types of drug design; one is Ligand based and the other Structure based drug design. Ligand based drug design is when you don’t know the structure. On the other hand, structure based drug design is when you do know the structure. Methods of drug design: 2.1.1Ligand-based Ligand based drug design, which is also sometimes referred to as indirect drug design, depends on the information given of other molecules that attach to the biological object. A pharmacophore model can be derived by using these other molecules that attach to the biological object. A pharmacophore is a theoretical description for molecular features that are essential in order to obtain molecular recognition of ligand by a biological macromolecule, a very large molecule. This defines the minimum essential structural features a molecule needs to have for it to attach to the object. In other words a model of the biological object can be built based on the information obtained of what attach to it and this model can also be used for designing new molecular objects that act together with the biological object. On the other hand, a quantitative structure activity relationship which correlation between calculated properties of molecules and their experimentally determined biological activit y, can be derived. These quantitative structure activity relationships in turn can be used to predict the activity of new analogues (Ligand-based drug design, 2014). 2.1.2Structure based The other method is called structure-based drug design. Structure based drug design, which is also referred to as direct drug design, depends on the information given about the three dimensional structure of the biological object gained from methods such as x-ray crystallography or NMR spectroscopy. If an experimental structure of an object is not available then it can be possible to make a homology model of the object based on the experimental structure of a related protein. Using the structure of the biological object candidate drugs that are predicted to attach to the high affinity and selectivity to the object can be designed using interactive graphics and the intuition of a medicinal chemistry or various automated computational procedures to suggest new drug candidates. The knowledge about the structural dynamics and electronic properties about ligands increased with more information concerning three dimensional structures of bimolecular objects. Current methods for structure ba sed drug design can be divided roughly into two categories. Fragment based Fragment based drug design involve Identifying low molecular weight compounds that weakly attach to a biological object macromolecule and will then be modified or connected to yield potent inhibitors. The specificity of these low difficulty and low affinity molecules has rarely been discussed in the writings (Ncbi.nlm.nih.gov, 2014). Computational drug design Drugs and associated biologically active molecules can be studied, improved and discovered by using computational chemistry in computer-aided drug design. In computer-aided drug design the most important aim is to predict if a certain molecule will attach to an object and if that is the case then how strongly does it attach. Often molecular dynamics or molecular mechanics are mostly used to predict the conformation of the small molecule and to model conformational changes in the biological object that might occur when the small molecule attach to it. An estimation of the binding affinity can also be obtained by the use of molecular mechanics methods. Likewise, information based scoring function can also be used in order to obtain binding affinity predictions (Young, 2009). The methods mentioned use statistical techniques such as linear regression, neural nets, machine learning, etc. This is used in order to derive estimated binding affinity equations by adding experimental affinities to computationally derived communication energies among the object and the molecule. If it is possible, the computational method will succeed in estimating affinity before a compound is fused. Therefore, in principle, just a single compound is needed to fuse. This is more efficient and will save a lot of time and money. However, the current computational methods available are not as perfect yet. At its best the computational methods gives just qualitatively accurate approximations of affinity. At the moment it still requires a few repetition of design, fusion and tests until a desired prime drug is found (Young, 2009). List of reference: Ssci-inc.com. 2014. Crystallization Impact on the Nature and Properties of the Crystalline Product. [online] Available at: http://www.ssci-inc.com/Information/RecentPublications/ApplicationNotes/CrystallizationImpact/tabid/138/Default.aspx [Accessed: 8 Mar 2014]. Drug design. 2014. [e-book] Available through: strbio.biochem.nchu.edu.tw https://www.google.co.uk/url?sa=trct=jq=esrc=ssource=webcd=3cad=rjauact=8ved=0CEIQFjACurl=http://strbio.biochem.nchu.edu.tw/classes/special%20topics%20biochem/course%20ppts/course3.pdfei=b1YnU4D9BPC00QXdooHIDgusg=AFQjCNHxw8n3fRX0CfwB5yUQ9JXkts-vgA [Accessed: 17 Mar 2014]. Ligand-based drug design. 2014. [e-book] Available through: strbio.biochem.nchu.edu.tw https://www.google.co.uk/url?sa=trct=jq=esrc=ssource=webcd=3cad=rjauact=8ved=0CEIQFjACurl=http://strbio.biochem.nchu.edu.tw/classes/special%20topics%20biochem/course%20ppts/course3.pdfei=b1YnU4D9BPC00QXdooHIDgusg=AFQjCNHxw8n3fRX0CfwB5yUQ9JXkts-vgA [Accessed: 17 Mar 2014]. Young, D. C. 2009. Computational drug design. Hoboken, N.J.: Wiley. Ncbi.nlm.nih.gov. 2014. Fragment based drug design: from experimental [Curr Med Chem. 2012] PubMed NCBI. [online] Available at: http://www.ncbi.nlm.nih.gov/pubmed/22934764 [Accessed: 18 Mar 2014].