B. Controlled Drug Release by Activation:
i) Osmotic Pressure-Activated Drug delivery
A brief of osmotically active systems have already been discussed in Part I of this article. Osmotically acting implantable device can be represented by Alzet Osmotic Pump.
Alzet Osmotic Pump
In such a device, the drug reservoir is contained inside a collapsible, impermeable polyester bag, whose external surface is coated with a layer of osmotically active salt. This reservoir compartment is then sealed inside a rigid housing walled with semi permeable polymer membrane.
At the implantation site, the water content in the tissue fluid will penetrate through the semi permeable membrane to dissolve the osmotically-active salt, creating an osmotic pressure in the narrow spacing between the flexible reservoir wall and the rigid semi permeable housing.
Under the osmotic pressure created, the reservoir compartment is reduced in volume and the drug solution is forced to release at a controlled rate through the flow moderator. By varying the drug concentration in the solution, different amounts of drug can be released at constant rate, for a duration of 1-4 weeks. Table 1 enlists few drugs delivered by miniature osmotic pumps.
ii) Vapor Pressure-Activated Drug Delivery
In this mode of controlled drug delivery, the drug reservoir, in a solution formulation, is controlled inside an infusate chamber, which is physically separated from the vapor chamber by a freely movable bellow. The vapor chamber contains a vaporizable fluid, e.g. fluorocarbon, which vaporizes at body temperature and creates a vapor pressure.
Under the vapor pressure created, the bellows moves upward and forces the drug solution in the infusate chamber to release, through a series of flow regulator and delivery canal, into the blood circulation at a constant flow rate.
A typical example is the development of Infused, an implantable infusion pump, for the constant infusion of heparin for anticoagulation treatment, of insulin for antidiabetic medication and of morphine for patients suffering from the intensive pain of terminal cancer.
iii) Magnetism-Activated Drug Delivery
Macromolecular drugs, such as peptides, have been known to release only at a relatively low rate from a polymeric drug delivery device. This low release rate has been improved by incorporating a magnetism triggering mechanism into the polymeric drug delivery device and a zero-order drug release profile has also been achieved by a hemisphere shaped geometry design.
By combining these two approaches, a subdermally implantable, magnetic-modulated hemispheric drug delivery device has been developed. It is fabricated by positioning a donut-shaped magnet at the center of a biocompatible polymer matrix, which contains a homogeneous dispersion of macromolecular drugs at a rather high drug to polymer ratio to form a hemispheric magnetic pellet.
The hemispherical pellet is then coated with a pure polymer e.g. ethylene-vinyl acetate copolymer or silicone elastomers on all sides, except the cavity at the center of the flat surface, to permit the release of macromolecular drug only through the cavity.
iv) Ultrasound-Activated Drug Delivery
It was recently discovered that ultrasonic wave can also be utilized as an energy source to facilitate the release of drug at a higher rate from polymeric drug delivery device containing a bioerodible polymer matrix. The potential application of ultrasonic wave for the modulation of drug release is still undergoing evaluation.
v) Hydrolysis-Activated Drug Delivery
This type of implantable therapeutic system is fabricated by dispersing a loading dose of solid drug, in micronized form, homogeneously through a polymer matrix made from bioerodible or biodegradable polymer, which is then molded into a pellet - or bead-shaped implant.
The controlled release of the embedded drug particles is made possible by the combination of polymer erosion through hydrolysis and diffusion through polymer matrix. The rate of drug release is determined by the rate of biodegradation, polymer composition and molecular weight, drug loading, and drug / polymer interactions.
i) Osmotic Pressure-Activated Drug delivery
A brief of osmotically active systems have already been discussed in Part I of this article. Osmotically acting implantable device can be represented by Alzet Osmotic Pump.
Alzet Osmotic Pump
In such a device, the drug reservoir is contained inside a collapsible, impermeable polyester bag, whose external surface is coated with a layer of osmotically active salt. This reservoir compartment is then sealed inside a rigid housing walled with semi permeable polymer membrane.
At the implantation site, the water content in the tissue fluid will penetrate through the semi permeable membrane to dissolve the osmotically-active salt, creating an osmotic pressure in the narrow spacing between the flexible reservoir wall and the rigid semi permeable housing.
Under the osmotic pressure created, the reservoir compartment is reduced in volume and the drug solution is forced to release at a controlled rate through the flow moderator. By varying the drug concentration in the solution, different amounts of drug can be released at constant rate, for a duration of 1-4 weeks. Table 1 enlists few drugs delivered by miniature osmotic pumps.
ii) Vapor Pressure-Activated Drug Delivery
In this mode of controlled drug delivery, the drug reservoir, in a solution formulation, is controlled inside an infusate chamber, which is physically separated from the vapor chamber by a freely movable bellow. The vapor chamber contains a vaporizable fluid, e.g. fluorocarbon, which vaporizes at body temperature and creates a vapor pressure.
Under the vapor pressure created, the bellows moves upward and forces the drug solution in the infusate chamber to release, through a series of flow regulator and delivery canal, into the blood circulation at a constant flow rate.
A typical example is the development of Infused, an implantable infusion pump, for the constant infusion of heparin for anticoagulation treatment, of insulin for antidiabetic medication and of morphine for patients suffering from the intensive pain of terminal cancer.
iii) Magnetism-Activated Drug Delivery
Macromolecular drugs, such as peptides, have been known to release only at a relatively low rate from a polymeric drug delivery device. This low release rate has been improved by incorporating a magnetism triggering mechanism into the polymeric drug delivery device and a zero-order drug release profile has also been achieved by a hemisphere shaped geometry design.
By combining these two approaches, a subdermally implantable, magnetic-modulated hemispheric drug delivery device has been developed. It is fabricated by positioning a donut-shaped magnet at the center of a biocompatible polymer matrix, which contains a homogeneous dispersion of macromolecular drugs at a rather high drug to polymer ratio to form a hemispheric magnetic pellet.
The hemispherical pellet is then coated with a pure polymer e.g. ethylene-vinyl acetate copolymer or silicone elastomers on all sides, except the cavity at the center of the flat surface, to permit the release of macromolecular drug only through the cavity.
iv) Ultrasound-Activated Drug Delivery
It was recently discovered that ultrasonic wave can also be utilized as an energy source to facilitate the release of drug at a higher rate from polymeric drug delivery device containing a bioerodible polymer matrix. The potential application of ultrasonic wave for the modulation of drug release is still undergoing evaluation.
v) Hydrolysis-Activated Drug Delivery
This type of implantable therapeutic system is fabricated by dispersing a loading dose of solid drug, in micronized form, homogeneously through a polymer matrix made from bioerodible or biodegradable polymer, which is then molded into a pellet - or bead-shaped implant.
The controlled release of the embedded drug particles is made possible by the combination of polymer erosion through hydrolysis and diffusion through polymer matrix. The rate of drug release is determined by the rate of biodegradation, polymer composition and molecular weight, drug loading, and drug / polymer interactions.
