Chemically Controlled Drug Delivery Systems

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Controlled drug delivery systems are being developed at a high rate because of the many advantages they offer in therapy. One advantage is their ability to deliver the active drug at a constant rate over a prolonged period, without delayed onset of action and without interference by gut physiology or other external conditions.

The precision in which the rate of drug release is known reduces the risk of side effects. It also increases patient compliance due to longer periods between dosing. Finally, it achieves better therapeutic effect as a result of all these factors.

Among these novel drug delivery systems are the chemically-controlled systems. These are dependent upon chemical reaction to release the drug from the polymer within which it is contained. The polymer is bioerodible, which means that the device will degrade and doesn’t need to be removed from the body after use. The process through which these polymers pass through a human body must be verified through rigorous preclinical testing, in order to ensure their safety.

Robert S. Langer (MIT) Part 1: Advances in Controlled Drug Release Technology: An Overview

Mechanisms of Action

The use of chemically-controlled drug delivery systems relies on one of two main mechanisms:


The bioerosion system, also called the biodegradation system, is based upon the degradation of the polymer within which the drug is uniformly distributed, into smaller molecules which are readily soluble in water.

In most cases, the polymer matrix controls the release of the drug which is evenly dispersed within it. The breakdown of the polymer leads to the entry of water, which causes the drug to dissolve on contact and be released.

The factors which control the release rate include:

  • The hydrophilic nature of the polymer
  • The porosity of the device
  • The presence of any components which can dissolve in water

These characteristics determine whether the water can spread throughout the system or remain confined to the surface alone.

In the first case, the polymer is eroded throughout the entire matrix, known as bulk erosion. It is characterized by an initial superficial degradation of the polymer with drug release, followed by the eventual rapid breakdown of the whole matrix leading to a sudden release of the rest of the drug.

When the polymer is hydrophobic, it repels water from entering inside the device, causing the erosion of the polymer to remain superficial throughout the drug release period. The device is called a surface-eroding device. The drug release rate is then given by the following equation:

dM/dt = KS

K being a constant of the drug concentration within the matrix and rate of erosion of the polymer, while S is the surface area. The rate of decrease of surface area with time is the critical factor in determining the rate of reduction of drug release. A device shaped like a slab has the greatest area in relation to its volume, while spherical devices have the highest area: surface ratio, and thus the fastest rate of decrease in release rate over time.

The slab shape is the geometry best suited to a constant rate of drug release using this mechanism. The benefit of ensuring a constant surface area with time is the ability to achieve zero-order kinetics in drug release and to avoid having a ghost matrix.

Robert S. Langer (MIT) Part 2: Drug Delivery Technology: Present and Future

Biodegradable and Water-Soluble Polymers

Biodegradable and water-soluble polymers are thus an intensive area of research. These include:

  • Polylactides
  • Polyglycolides
  • Polylactide-co-glycolides
  • Polyanhydrides
  • Polyorthoesters

Though this is theoretically superior to the first type of mechanism, the fact remains that the manufacturing process is not fool-proof: microscopic defects do occur in the polymer. Additionally, most drugs are water-soluble and most polymers are hydrophilic.

As a result, most of these systems end up as bulk-eroding devices and the rate of drug release is controlled by both bulk and surface erosion. This means that it is quite difficult to predict just how much drug will be released.

On the other hand, it is possible to factor in changes in the shape and size of the device, how much drug is carried in each, what and how much excipients are added, including polymeric characteristics such as its rate of degradation and molecular weight, all of which can be regulated to help determine the actual drug release rate.

Pendent Chain

By this mechanism, the drug is not incorporated physically into the polymer.  Instead, it is attached to its backbone through a reactive chemical bond which easily gives way in the presence of water or certain enzymes. This hydrolysis of the bond leads to drug release. The pendent chain is the term used for the polymer backbone itself. When it is water-soluble the drug can be carried to targeted cells or organs for slow controlled release.

However, an insoluble pendent chain functions more as a reservoir of the drug. The shape of the device and the water-solubility of the polymer backbone can both help regulate how fast the chemical bond degrades to release the drug.

One significant negative aspect of this type of chemically-controlled drug delivery system is commercial: the presence of a covalent linkage between the drug and the polymer means that the resulting molecule may well be defined as a new one, requiring stringent safety testing by regulatory bodies before approval is given. This means there is often a delay before the device can be released, which pushes up costs and therefore  accessibility.

Further Reading

Last Updated: Feb 26, 2019

Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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