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Ege University / Chemical Engineering Department

Ion Exchange in Pharmaceutical Industry

Prepared by ; Mine KK - 05070008943

Submitted to : Prof.Dr. Nalan KABAY

Contents
General

properties of ion exchange resins in Pharmaceutical Industry ,

Usage

area in Pharmaceutical Industry.

Ion exchange resins are cross-linked, water insoluble, polymer-carrying,ionizable functional groups.[1]

Ion exchange resins have been used for many years in pharmaceutical formulations. Their uses have large range .[2]

Properties of pharmaceutical grade ion exchange [2] fine , free-flowing powders, particle size of 25-150 microns, contain functional groups capable of exchanging ions and/or ionic groups, insoluble in all solvents , all pH levels, not adsorbed by the body, do not have a defined moleculer weight, be non-toxic and very safe.

Drugs can be loaded onto the resins by an exchanging reaction , and hence, a drug-resin complex (drug resinate) is formed.[1]Following figure shows are the equlibrium reaction between an anion exchange resin and drug molecule.[3] It is important to recognize that this is a reversible reaction, the equlibrium position of which will depend on the environment n which the drug and ion exchange resin are found.[2]

Factors controlling the equlibrium constant include the following[2] ;

Moleculer weight, pKa of drug and resin, Solvent, Solubility, Temperature, Hydrophobicity Concentration of competing ions

The loaded resin is often reffered to as a resinate . The typical properties of resinates are shown in following . The properties are very similar to those the original ion exchange resin.[2]

Physical Properties of Resinates ; o fine, free- flowing powders, o particle size similar to the starting polymer, o contain the active pharmaceutical ingredient in salt form, o do not have a melting point.

The performance of resinate is governed by several factors such as[3] ; o pH and temperature of drug solution, o Molecular weight and charge ,intensity of the drug and ion exchange resin, o Geometry, o Mixing speed, o Ionic strength of the drug solution, o Degree of cross linking and particle size of the ion exchange resin, o The nature of the solvent, o Contact time between the drug species and the ion exchange resin.

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Ion exchange resins are used in the pharmaceuticals, not only for catalyzing certain reactions but also for isolating and purifying pharmaceutical active ingredients. Three ion exchange resins are used as active ingredients ; o Polystyrene sulfonate o Colestipol o Cholestramine [4]

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Polystyrene Sulfonate ; is strongly acidic ion exchange resin and is used to treat hyperkalemia.[4] The kidneys continuously remove potassium . When kidney function is failing, it may be necessary to remove potassium from the intestinal tract by artificial means. This can be achieved by using Polystyrene Sulphonates, in either the sodium or calcium form.As the resins pass through the intestinal tract they exchange the sodium or calcium on the resin for potassium. The adsorbed potassium cannot pass into the blood and continues through the body without being released . Introduced into clinical use in the early 1950s, such resins are now widely used in the treatment of acute and chronic hyperkalaemia, in addition to controlling serum potassium levels in patients undergoing renal dialysis.[5]

Polystyrene Sulphonates in Sodium Form

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Cholestyramine ; is a strongly basic ion exchange resin and is used to treat hypercholesterolemia. Cholestyramine is a bile acid sequestransts, which binds bile in the gastrointestinal to prevent its reabsorption. It is a strongion exchange resin, which means that it can exchange its chloride anions with anionic bile acids in the gastrointestinal tract and bind them strongly in the resin matrix. The functional group of the anion exchange resin is a quaternary ammonium group attached to an inert styrenedivinylbenzene copolymer. Cholestyramine removes bile acids from the body by forming insoluble complexes with bile acids in the intestine, which are then excreted in the feces. When bile acids are excreted, plasma cholesterol is converted to bile acid to normalize bile acid levels. This conversion of cholesterol into bile acids lowers plasma cholesterol concentrations.[4]

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Colestipol ; is a weakly basic ion exchange resin and is also used to treat hypercholesterolemia. Colestipol is a vile acid sequestransts used to lower blood cholestrol, specifically low density lipoprotein (LDL).Like cholestyramine, colestipol works in the gut by trapping bile acids and preventing them from being reabsorbed. This leads to decreased enterohepatic recirculation of bile acids, increased synthesis of new bile acids by the liver from cholesterol, decreased liver cholesterol, increased LDL receptor expression, and decreasing LDL in blood.[4]

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Ion exchange resins are also used as excipients in pharmaceutical formulations such as tablets, capsules and suspensions. In these uses the ion exchange resin can have several different functions[4] ;

Taste

masking Sustained and controlled release Tablet disintegration Improving the chemical stability of the active ingredients.

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Taste Masking ;
The scope of Ion exchange resins for masking the undesirable taste of pharmaceuticals is unlimited.Since the drug resin complex is insoluble, it has virtually no taste, so that even bitter drugs lose their taste when converted into a drug resinate with proper selection of ion exchange resins. The drug resinate can be made sufficiently stable so that it does not break down in the mouth and so that the patient does not taste the drug when it is swallowed. However, when the drug resinates come in contact with gastrointestinal fluid, usually the acid of the stomach, the complex is broken down quickly and completely.[3]

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Sustained and controlled release; Sustained release formulations ensure that drug is released continuously into the body at a slower, but steady rate. The release of drugs from ion exchange resins depends upon a aeries of ionic reactions between various body fluids and the drug-resin complex. The rate of release of drug can be controled by varying the particle size, degree of crosslinking and the chemistry of resin. The release profile can almost be tailor made to suit a particular application.[6]

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Tablet Disintegrat ;
Ion exchange resins, because of their excellent swelling property when immersed in water, can be used as a tablet disintegrating agent. [7]

Resins although insoluble, have great affinity for water and hence, act as disintegrant.[1]

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The advantages of ion exchange resins over conventional disintegratiing agents include :

The rate of permeation of water and subsequent swelling is very fast and cuts down the disintegrating time. Ion exchange resins do not have adhesive tendency on hydration ; hence tablets disintegrate evenly without lumps. Ion exchange resin is effective in low concentration as a disintegrant. After incorporation of ion exchange resins, the hardness of the tablets increases. [3]

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Drug stabilization ;
The drug resinate is frequently more stable than the original drug. Vitamin B12 has a shelf-life of only a few months, but the resinate is stable for more than two years. Another example is nicotine; it discolors quickly on exposure to air and light, but the resinate, used in nicotine chewing gums and lozenges, is much more stable. [7]

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I try to explain ;
Generally

properties of resin and resinate ,

Usage

area of Pharmaceutical ion exchange

resins.

I hope it is clear and concise !

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REFERENCES
1.

2. 3.

4. 5. 6. 7.

Mahore J. G, Wadher K. J. ,Umerkar M. J, Bhoyar P.K., ION EXCHANGE RESINS: PHARMACEUTICAL APPLICATIONS AND RECENT ADVANCEMENT , Volume 1 ,Issue 2 ,March-April 2010 , Article 002 Dr. L. HUGHES ,New Uses of Ion Exchange Resins in Pharmaceutical Formulation , Rohm and Haas Research Laboratories Spring House Sunil K. Bajpai , Manjula Bajpai , Sutanjay Saxena , Ion Exchange and Solvent Extraction,,A series Advances,Volume 16,Ion Exchange Resins in Drug Delivery ,2007 http://en.wikipedia.org/wiki/Ion-exchange_resin#Pharmaceuticals (last update : 25.04.2012) http://www.purolite.com/customized/uploads/pdfs/AppGuide_ActivePhpr oducts9_10_08.pdf (last update :02.05.2012) http://www.thermax-usa.com/tulsion/pharmaceutical-applications#startOfPageId51 (last update : 25.04.2012 ) http://fabad.org/fabad.org/pdf/volum32/issue2/91-100.pdf

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