Ion exchange and pH controlled drug delivery systems

Ion exchange and pH controlled drug delivery systems

Session Objectives

By the end of this session, students will be able to:

       Explain the role of ion exchange resins in the formulation of CRDF

       Discuss factors affecting the drug release and pharmaceutical applications of IER delivery systems

       Describe the process of pH variable on the drug release from the dosage form

       Apply the principles of ion exchange resins and pH dependent in dosage form  development

Definition

       Ion exchange is a reversible process in which ions of like sign are exchanged between liquid and solid when in contact with a highly insoluble body. The drug is released from the resinate by exchanging with  ions in the gastrointestinal fluid, followed by drug diffusion Due to the presence of high molecular weight water insoluble polymers, the resins are not absorbed by the body and are therefore inert

Advantages

       Ion-exchange systems are advantageous for drugs that are highly susceptible to  degradation by enzymatic process

       A major advantage of ion exchange system is low running cost

       It requires little energy and the regenerated chemicals are cheap

       well maintained, resin beds can last for many years before replacement

Limitations

       Limitation is that the release rate is proportional to the concentration of the  ions present in the area of administration

       The release rate of drug can be affected by variability in diet, water intake and individual intestinal content

Classification of Ion exchange resin

1. Cation exchange resin

a) Strong acid

b) Weak acid

2. Anion exchange resin

a) Strong base

b) Weak base

Ion Exchangers

Naturally occurring and synthetic

       Inorganic ion exchangers have greater selectivity and better disposal options than organic resin

       Organic ion exchangers are reliable and efficient in water coolant systems

       Mineral compounds such as bentonite, Kaolinite and Illite and Zeolites  such as analcite, chabazite, sodalite and clinoptilolite are naturally  occurring inorganic ion exchangers

       Zeolites, Titanates and silico-titanates, transition metal hexacyanoferrates are  inorganic synthetic ion exchangers

       Polysaccharides such as cellulose, algic acid, straw and peat, proteins such as  casein, keratin and collagen and carbonaceous materials such as charcoals,  liquites and coals are naturally occurring organic ion exchangers

Role of IER in Controlled Drug Delivery Systems

       The major drawback of controlled release is dose dumping, resulting in increased risk of  toxicity

       The usage of IER during the development of controlled release formulations plays a  significant role because of their drug retarding properties and prevention of dose  dumping

       The drug resinates can also be used as a drug reservoir, which has caused a change of the  drug release in hydrophilic polymer tablets

       The use of IER into drug delivery systems includes physico-chemical stability, inert nature,  uniform size, spherical shape assisting coating and equilibrium driven reproducible drug  release in ionic environment

       Drug molecules attached to the resins are released by appropriate charged ions in  the gastrointestinal tract, followed by diffusion of free drug molecules out of the  resin as shown below

Resin- Drug +   + X +  à Resin-.... X + + Drug +

Resin+ Drug - + Y -  à Resin+...  Y - + Drug -

Where, X and Y are ions in the gastrointestinal tract.

       IER have been used as drug carriers in pharmaceutical dosage forms for controlled  release formulation

       The prolonged release of the active drug is accomplished by providing a semi-  permeable coating around discrete, minute, ion exchange resin particles with which  the drug component has been complexed to form an insoluble drug resin complex

 

       The physical and chemical properties of the IER will release the drug more  uniformly than that of simple matrix formulations

Important Properties of IER

Ø  Particle size and form

Ø  Porosity and swelling

Ø  Cross linkage

Ø  Available capacity

Ø  Acid base strength

Ø  Stability

Ø  Purity and toxicity

Applications of IER

Pharmaceutical applications

       Taste masking

       Eliminating polymorphism

       Improving the dissolution of poorly soluble drugs

       Improving stability

       Improving physical characteristics

Drug delivery applications

       Oral drug delivery

       Nasal drug delivery

       Transdermal drug delivery

       Ophthalmic drug delivery

Introduction to pH controlled systems

The variable nature of the chemical environment throughout the length of the GIT is a further constraint on dosage form design.

Drugs administered orally would encounter a spectrum of pH ranging from 7 in mouth, 1-4 in the stomach, and 5-7 in the small intestine.

Since most drugs are either weak acids or weak bases, their release from formulation is pH dependent.

This type of system is designed for the controlled release of acidic (or basic) drugs in GIT at a rate independent of the variation in GI pH by formulating them with sufficient buffering agents.

It is prepared by first blending an acidic (or basic) drug with one or  more buffering agents, e.g. a primary, secondary, or tertiary salt of  citric acid, granulating with appropriate excipients to form small  granules, and then coating the granules with GI fluid-permeable  film-forming polymer, e.g. cellulose derivatives.

Salts of amino acids, citric acid, phosphoric acid or tartaric acid are commonly used.

The polymer coating controls the permeation of GI fluid. The GI fluid permeating into the device is adjusted by the buffering agents to an appropriate constant pH, at which the drug dissolves and is delivered through the membrane at a constant rate regardless of the location of the device in the alimentary canal.

pH Activated Drug Release

       This type of drug delivery permits targeting the delivery in a region with selected pH

       In this system the gastro intestine liable drug is coated with an  intestinal fluid soluble and insoluble polymer i.e. Ethyl cellulose and  Hydroxy Methyl Cellulose Phthalate (HMCP)

       The HMCP polymer gets degraded in the small intestine and produces  pores in the ethyl cellulose polymer coating

       The drug then releases from the micro porous membrane at a  controlled rate

Summary

       Ion exchange is a reversible process in which ions of like sign are  exchanged between liquid and solid when in contact with a highly  insoluble body

       The drug is released from the resinate by exchanging with ions in the gastrointestinal fluid, followed by drug diffusion

       The use of IER into drug delivery systems includes physico-chemical  stability, inert nature, uniform size and spherical shape which exhibits  reproducible drug release in ionic environment

       The physical and chemical properties of the IER will release the drug more uniformly than that of simple matrix formulations

       The pharmaceutical applications of IER controlled delivery systems  includes : taste masking of drug, improving dissolution of poorly  soluble drugs, physical characteristics and stability

       pH activated drug delivery permits targeting the drug release in a  region with selected pH. It is designed for the controlled release of  acidic or basic drugs independent of G.I. pH variablity

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