IV) TRANSDERMAL SYSTEMS:
The transdermal route of drug administration offers several advantages over other methods of delivery. For some cases, oral delivery may be contraindicated, or the drug may be poorly absorbed. This would also include situations for which the drug undergoes a substantial first pass effect and systematic therapy is desired.
The skin, although presenting a barrier to most drug absorption, provides a very large surface area for diffusion. Below the barrier of the stratum corneum is an extensive network of capillaries. Since the venous return from these capillary beds does not flow directly to the liver, compounds are not exposed to these enzymes during absorption.
A most notable example of such a drug is nitroglycerin, which has been administered both sublingually and transdermally to avoid first-pass metabolism. Other drugs that have seen success in controlled transdermal delivery are testosterone, fentanyl, bupranolol and clonidine.
Transdermal controlled-release systems can be used to deliver drugs with short biological half-lives and can maintain plasma levels of very potent drugs within a narrow therapeutic range for prolonged periods. Should problems occur with the system, or a change in the status of the patient require modification of therapy, the system is readily accessible and easily removed.
One of the primary disadvantages of this method of delivery is that drugs requiring high blood levels to achieve an effect are difficult to load into a transdermal system owing to the large amount of material required. These systems would naturally be contraindicated if the drug or vehicle caused irritation to the skin.
Also, various factors affecting the skin, such as age, physical condition, and device location, can change the reliability of the system’s ability to deliver medication in a controlled manner. In other words, both the drug and the nature of the skin can affect the system design.
SKIN DEPOT EFFECT - Difference between transdermal drug delivery systems Vs. other delivery routes :-
When a transdermal patch is applied to the skin, the steady-state systemic dosage may not be reached for some time because of absorption of the drug in the skin. If skin absorption is large, the time required to saturate the skin with drug may be long compared to the time the device is on the skin. It is not possible then to simply equate the rate of drug delivery with the rate of appearance of drug in the systemic circulation even for device rate controlling systems.
For the majority of drugs, a plot of drug release from the device and drug absorption rate at the site of action has the general shape shown in this figure. Initially, there is a difference between the drug release from the device curve and drug systemic absorption curve, because some drug is immobilized in the skin. Ultimately, the skin absorption sites are saturated and the steady state is reached, when the rate of drug released equals the rate of appearance in the blood.
When the rate device is removed, drug release from the device abruptly halts. Release of drug absorbed in the skin, however, will continue for some time. In many cases, this depot effect may be sufficiently marked that the skin-loading time is comparable with the time the device is on the skin, so that the drug delivery does not reach steady state before the device is exhausted or removed.
However, if therapy involves repeated applications of transdermal patches, this may not matter since the depot effect due to one device will be compensated for by the release of drug from an earlier device. Nevertheless, the depot effect is a major factor to be taken into account in device design.
The transdermal route of drug administration offers several advantages over other methods of delivery. For some cases, oral delivery may be contraindicated, or the drug may be poorly absorbed. This would also include situations for which the drug undergoes a substantial first pass effect and systematic therapy is desired.
The skin, although presenting a barrier to most drug absorption, provides a very large surface area for diffusion. Below the barrier of the stratum corneum is an extensive network of capillaries. Since the venous return from these capillary beds does not flow directly to the liver, compounds are not exposed to these enzymes during absorption.
A most notable example of such a drug is nitroglycerin, which has been administered both sublingually and transdermally to avoid first-pass metabolism. Other drugs that have seen success in controlled transdermal delivery are testosterone, fentanyl, bupranolol and clonidine.
Transdermal controlled-release systems can be used to deliver drugs with short biological half-lives and can maintain plasma levels of very potent drugs within a narrow therapeutic range for prolonged periods. Should problems occur with the system, or a change in the status of the patient require modification of therapy, the system is readily accessible and easily removed.
One of the primary disadvantages of this method of delivery is that drugs requiring high blood levels to achieve an effect are difficult to load into a transdermal system owing to the large amount of material required. These systems would naturally be contraindicated if the drug or vehicle caused irritation to the skin.
Also, various factors affecting the skin, such as age, physical condition, and device location, can change the reliability of the system’s ability to deliver medication in a controlled manner. In other words, both the drug and the nature of the skin can affect the system design.
SKIN DEPOT EFFECT - Difference between transdermal drug delivery systems Vs. other delivery routes :-
When a transdermal patch is applied to the skin, the steady-state systemic dosage may not be reached for some time because of absorption of the drug in the skin. If skin absorption is large, the time required to saturate the skin with drug may be long compared to the time the device is on the skin. It is not possible then to simply equate the rate of drug delivery with the rate of appearance of drug in the systemic circulation even for device rate controlling systems.
For the majority of drugs, a plot of drug release from the device and drug absorption rate at the site of action has the general shape shown in this figure. Initially, there is a difference between the drug release from the device curve and drug systemic absorption curve, because some drug is immobilized in the skin. Ultimately, the skin absorption sites are saturated and the steady state is reached, when the rate of drug released equals the rate of appearance in the blood.
When the rate device is removed, drug release from the device abruptly halts. Release of drug absorbed in the skin, however, will continue for some time. In many cases, this depot effect may be sufficiently marked that the skin-loading time is comparable with the time the device is on the skin, so that the drug delivery does not reach steady state before the device is exhausted or removed.
However, if therapy involves repeated applications of transdermal patches, this may not matter since the depot effect due to one device will be compensated for by the release of drug from an earlier device. Nevertheless, the depot effect is a major factor to be taken into account in device design.
