Transdermal drug delivery systems fall into two broad categories:
Monolithic Transderm Therapeutic System:
A typical monolithic system therapeutic transderm system (TTS) has 3 layers, an impermeable backing, and an adhesive matrix that contains the drug. In this system, the matrix material controls the drug-diffusion rate from the device.
Initially the drug contained in the device is uniformly distributed throughout the polymer matrix, when the system is placed on the skin, the drug contained in the surface layers permeates into the skin first at a relatively rapid rate. As the surface layers of the polymer matrix become depleted of drug, the drug-release rate falls as the drug is removed from the interior of the device and must diffuse progressively further to reach the device surface.
Reservoir Transdermal Therapeutic System :-
This type of a device also has a backing and adhesive layer, but the drug is now contained in a reservoir, from which its diffusion is controlled by a separate rate-controlling membrane layer. The drug is usually contained within the reservoir as a suspension in a liquid or gel carrier phase.
On storage, a portion of the drug contained in the reservoir migrates into the membrane and adhesive layers. When the device is placed on the skin, this drug is released rapidly, giving an initial burst effect. Thereafter, drug release is controlled by the rule of drug diffusion through the membrane and adhesive layers to the skin.
This release will be maintained at a constant value so long as the solution inside the device reservoir is saturated. i.e. excess undissolved drug is present. Drug diffusing from the reservoir solution is then immediately replenished by dissolution of some of the excess drug.
When the last excess drug dissolves, the drug concentration drops below the saturation value and the drug-release rate falls. With this type of device, the release rate can be altered by changing the membrane thickness and permeability.
A final type of system, having drug-release kinesis intermediate between a monolithic and reservoir system, is obtained when a membrane is over coated onto a monolithic polymer matrix containing dispersed drug. The drug release is initially controlled by the membrane, but as the drug contained in the polymer matrix adjacent to the membrane is depleted the release rate falls because the drug must now diffuse through an increasingly thick layer of matrix.
Currently available marketed controlled TTS can be classified into 4 types as follows:
Most marketed systems are of the polymeric membrane-controlled type, representative of these is Transderm-Scop. This product is designed to deliver scopolamine over a period of days, without the side effects commonly encountered when the drug is administered orally.
The system consists of a reservoir containing the drug dispersed in a separate phase within a highly permeable matrix. This is laminated between the rate-controlling micro porous membrane and an external backing that is impermeable to drug and moisture.
The pores of the rate-controlling membrane are filled with a fluid that is highly permeable to scopolamine. This allows delivery of the drug to be controlled by diffusion through the device and skin. Control is achieved because, at equibrium, the membrane is rate limiting for drug permeation. To initiate an immediate effect, a priming dose is contained in a gel on the membrane side of the device.
Another drug that is popular for controlled transdermal release is nitroglycerin. Conventionally, this drug is administered sublingually, although the duration of action by this route is quite short. This is acceptable for acute anginal attacks, but not for prophylactic treatment.
Oral administration has the disadvantage that large fractions of the dose are lost to first-pass metabolism in the liver. Topical ointments have long been used for prophylactic treatment of angina, but their duration is only 4-8 hr and, in addition, are not aesthetically acceptable. The transdermal nitroglycerin devices employ a variety of systems to provide 24 hr delivery.
- Monolithic systems and
- Reservoir systems
Monolithic Transderm Therapeutic System:
A typical monolithic system therapeutic transderm system (TTS) has 3 layers, an impermeable backing, and an adhesive matrix that contains the drug. In this system, the matrix material controls the drug-diffusion rate from the device.
Initially the drug contained in the device is uniformly distributed throughout the polymer matrix, when the system is placed on the skin, the drug contained in the surface layers permeates into the skin first at a relatively rapid rate. As the surface layers of the polymer matrix become depleted of drug, the drug-release rate falls as the drug is removed from the interior of the device and must diffuse progressively further to reach the device surface.
Reservoir Transdermal Therapeutic System :-
This type of a device also has a backing and adhesive layer, but the drug is now contained in a reservoir, from which its diffusion is controlled by a separate rate-controlling membrane layer. The drug is usually contained within the reservoir as a suspension in a liquid or gel carrier phase.
On storage, a portion of the drug contained in the reservoir migrates into the membrane and adhesive layers. When the device is placed on the skin, this drug is released rapidly, giving an initial burst effect. Thereafter, drug release is controlled by the rule of drug diffusion through the membrane and adhesive layers to the skin.
This release will be maintained at a constant value so long as the solution inside the device reservoir is saturated. i.e. excess undissolved drug is present. Drug diffusing from the reservoir solution is then immediately replenished by dissolution of some of the excess drug.
When the last excess drug dissolves, the drug concentration drops below the saturation value and the drug-release rate falls. With this type of device, the release rate can be altered by changing the membrane thickness and permeability.
A final type of system, having drug-release kinesis intermediate between a monolithic and reservoir system, is obtained when a membrane is over coated onto a monolithic polymer matrix containing dispersed drug. The drug release is initially controlled by the membrane, but as the drug contained in the polymer matrix adjacent to the membrane is depleted the release rate falls because the drug must now diffuse through an increasingly thick layer of matrix.
Currently available marketed controlled TTS can be classified into 4 types as follows:
- Membrane permeation-controlled system in which the drug permeation is controlled by a polymeric membrane. Transderm-Scop (scopolamine;Ciba-Geigy)
- Adhesive dispersion-type system is similar to the foregoing but lacks the polymer membrane, instead the drug is dispersed into an adhesive polymer. Deponit (nitroglycerin; Wyeth)
- Matrix diffusion-controlled system in which the drug is homogeneously dispersed in a hydrophilic polymer, diffusion from the matrix controls release rate. Nitrodur (nitroglycerin; Key)
- Microreservoir dissolution-controlled system in which microscopic spheres of drug reservoir are dispersed in a polymer matrix. Nitrodisc (nitroglycerin; Searle)
Most marketed systems are of the polymeric membrane-controlled type, representative of these is Transderm-Scop. This product is designed to deliver scopolamine over a period of days, without the side effects commonly encountered when the drug is administered orally.
The system consists of a reservoir containing the drug dispersed in a separate phase within a highly permeable matrix. This is laminated between the rate-controlling micro porous membrane and an external backing that is impermeable to drug and moisture.
The pores of the rate-controlling membrane are filled with a fluid that is highly permeable to scopolamine. This allows delivery of the drug to be controlled by diffusion through the device and skin. Control is achieved because, at equibrium, the membrane is rate limiting for drug permeation. To initiate an immediate effect, a priming dose is contained in a gel on the membrane side of the device.
Another drug that is popular for controlled transdermal release is nitroglycerin. Conventionally, this drug is administered sublingually, although the duration of action by this route is quite short. This is acceptable for acute anginal attacks, but not for prophylactic treatment.
Oral administration has the disadvantage that large fractions of the dose are lost to first-pass metabolism in the liver. Topical ointments have long been used for prophylactic treatment of angina, but their duration is only 4-8 hr and, in addition, are not aesthetically acceptable. The transdermal nitroglycerin devices employ a variety of systems to provide 24 hr delivery.
