Purification of Pharmaceutical Products, Research Paper Example

Abstract

This site investigates the phenomena inherent to Liquid-liquid extraction with a focus on the use of interface between aqueous and organic layers. For means in production of pharmaceutical compounds in addition to other organic reagents. The technique described has been designated Liquid-liquid distribution by IUPAC, however is more commonly referred to as solvent extraction. The main applications of this method addressed here are in the study of inorganic and organic equilibria, separations in analytical chemistry, large scale industrial separation processes, Industrial waste treatment. The historical relevance, background theory and design applications are investigated.

Aqueous two-phase systems have important uses in the world today. Aqueous two-phase systems are generally made up of either a polymer and given salts or two polymers that are structurally distinct. These systems are essential the characterization, study and purification of biomaterial. This paper will represent the definition of aqueous two-phase systems, the theoretical information behind the workings of aqueous two-phase systems the different application of the aqueous two-phase systems. Furthermore, an overview of the history and the environmental impacts associated with aqueous two-phase systems is discussed.

Introduction

Background Information

The high cost of many downstream processing methods for the recovery of product is a significant problem in many bioengineering processes. Biotechnology has come a long way making it possible to produce many bio-products with large scale-scale production. Downstream processing methods with regards to biological materials requires purification techniques that are gentle enough to protect the biological activity. Many conventional methods are difficult to make on a larger scale which causes them to be very difficult and expensive to do. Extraction of pharmaceuticals using an aqueous two phase process is one way to do it which is easier and more economical.

ATPS (aqueous two-phase systems) offer an economical, environmentally friendly and effective method of separation. ATPS is currently the most widely accepted technique of separation as partial purification, concentration and clarification can be realized in a procedure that shortens the process of protein purification. ATPS has a considerable advantage over the conventional liquid-liquid. Compared to conventional liquid-liquid extraction techniques, there are huge advantages of ATPS. These include:

• low interfacial tension and high biocompatibility
• low material costs
• relatively high capacity
• good resolution
• high separation yield
• low degradation of biomolecules
• ease of scale-up

This sort of system was outlined by Berjerinck late in the nineteenth century and brought back to light in the 1950’s by Albertson to isolate and separate plant organelles and viruses. Albertson’s employed the aqueous two-phase system to recover Bio molecules. ATP was later used in the recovery of metallic ions, and has also been used in sulphide minerals extraction and crystallization of organic salts as a method of extracting the organic salts. The liquid-liquid extraction is possible for both aqueous and non-aqueous systems. The non-aqueous system can effectively employ the liquid-liquid extraction in the case where there is molten metal has interacted with molten salts.

The important factor in carrying out separation with an aqueous two phase system is manipulating the phase composition to acquire good partition coefficients and selectivity for the material desired. It is essential that any separation technique that is employed in the in the purification, concentration and separation of pharmaceutical products, biomolecules and proteins be economical, effective and environmentally friendly. There are different types of aqueous two-phase extraction techniques that can be applied. These include Polymer–polymer systems, Polymer–salt systems and Ionic liquids.

Liquid-liquid extraction can be applied in numerous areas of study. These include: the purification of DNA, analytical chemistry, in the purification of anomia and in the food industry (The PEG–NaCl system). It is essential that the process be as accurate as possible. Measures of effectiveness are employed in quantifying and/or measuring the effectiveness of the liquid-liquid extraction process. The Distribution ratio indicates how well a species has been extracted. The distribution is held as equivalent to the concentration of the solute in question by its concentration when the solute is in the aqueous phase. The separation factor is used to measure a system’s capacity to separate two solutes. The determination factor is used to depict the ability of the system to get rid of any contaminants present in the initial solution.

Liquid-Liquid Extraction has numerous industrial applications that are pertinent to the validity, feasibility and practicality of the process. Since the liquid-liquid extraction process is founded on the principle of the difference in chemical structures, it is the ideal process in different processes of separation. They include;

• Liquid-Liquid Extraction for Biotechnology. For example extraction of valuable products from fermentation broth.
• Recovery of tightly hydrogen-bonded organics from water. For example formic acid, acetic acid and formaldehyde.
• Removal of high boiling organics from wastewater, such as, aromatics, aniline and nitrated phenol.
• Neutralization/washing of acids or bases from organic stream. For example, chloro-benzene compounds, nitrated organics and acrylates.
• Purification of heat sensitive materials, For example, flavors, food products pharmaceuticals and fragrances.

Recovery of products from reactions. For example adiponitrile and caprolactam (use in the production of nylon, agricultural chemicals and acrylic acids.

Theory

Liquid-Liquid Extraction is a solvent separation technique that extracts a given compound from a solvent, A, to another solvent, B, where both solvent are immiscible. The separation funnel is the most common technique of liquid-liquid extraction. The separation of solutes is influenced by their solubilties in different liquids.

How and why does the separation technology work?

The extraction process in liquid-liquid extraction is based on different solubilities of components in two immiscible liquids where the components of interest to be recovered are extracted from the feed with the assistance of a solvent. The two liquids must be significantly contacted and separated from each other again. Multiple stages and counter current flows are required to achieve high purities and yield2.

For this to process to work the components need to meet certain specifications. The main criteria for the material being extracted is an ideal partition coefficient (K), a high selectivity and an easy separation from the extracted product.

The solute enriched solvent stream is termed extract likewise the solute depleted feed is termed raffinate. Note; the driving force of this separation process relies on differences in relative solubilities between the two immiscible streams. This method is also known as Solvent extraction or partitioning.1

As depicted in the figure above, the feed liquid that contains the compund to be seperated is placed into a container. The feed is the initial solution that has to be sperated. The feed contains the solute and the crarrier liquid. This is then mixed with the extraction liquid that is immiscible through the process of agitation. The extraction liquid is the solvent which a pure liquid before contact with the feed. The compunds to be extracted are redistributed in the liquid pahses that are not distinct or clear at first. The process of agitation is continued until and equilbriums is achieved. Agitation is brought to a halt and the two liquids present two clear and distinct phases. During contact, there is a mass transfer of the solute from the feed to the colvent. During this time, there is also a minimal transfer of the carrier liquid to the solvent. After setlting, the two phases are then seperated. After the solvent carries the solute and seperates from the carrier liquid gradually. The product that is ricjh with the solvent is reffered to as the extract. The remaining liquid from which the solvet-potent product has been xytracted from is known as the raffinate.

It important to note that some experiments have the solute as the desired end-product, making the extraction stream as the required stream. In other cases, the raffinate is the required stream as the contaminants to be romeved are the solutes. In order for liquid-liquid extraction to be feasible, two criteria have to be met;

• The solvent and feed used in the processs bothathave to be considerably immiscible. The liquids cannot at any goven point in time during contant be able to mix, creating a new compund.
• The compnents that are to be extrcated from the feed have be alble to prefferntially distribute in the solvent as opposed to the solvent.

What provides the driving force?

The driving force for the motion of droplets is the pair of liquids are a low mutual solubility and different in density. In many multistage extractors the liquids are flowing counter-currently where viscosity and interfacial tension can also be important driving forces. Almost all liquid-liquid extraction processes have one of the liquids dispersed into the second liquid in the form of droplets where performance is driven by the adapted droplet size and a uniform “hold-up” profile throughout the column.

Phase Equilibrium

Design of extraction processes and equipment is based on mass transfer and thermodynamic data. Among such thermodynamic data, phase equilibrium data for mixtures, which is the distribution of components between different phases. Two main approaches can be taken when developing thermodynamic equations for the correlations and prediction of equilibrium data. Both are heavily rooted in thermodynamic expressions that operate bounded by experimental data.