An Over View of Implantable Therapeutic Systems
Apart from the conventional routes of administration, for treatment of various diseases drugs can also be incorporated as Implants. Here is the brief note on such therapeutic systems.
REQUIREMENTS OF DRUGS:
- Should be bio stable, biocompatible with minimal tissue implant interactions.
- Non toxic, non carcinogenic.
- Removable if required.
- Should release the drug at a constant, programmed rate for a predetermined duration of medication.
APPROCHES USED:
A. Controlled drug release by diffusion:
- Membrane Permeation – Controlled Drug Delivery: In this mode of controlled drug delivery, the drug reservoir is encapsulated within a compartment totally enclosed by a rate-controlling polymeric membrane. The drug reservoir can be either drug solid particles or a dispersion (or a solution) of drug solid particles in a liquid or a solid type dispersing medium. The polymeric membrane can be fabricated from a homogeneous or heterogeneous non porous polymeric material or a microporous (or a semipermeable) membrane. The encapsulation of drug reservoir inside the polymeric membrance can be accomplished by moulding, capsulation, microencapsulation, or other techniques. Different shapes and sizes of drug delivery devices can be fabricated.
Eg. Progestasert IUD: In such a device, the drug reservoir, which is a suspension of progesterone crystals in liquid silicone polymer, is encapsulated in a T shaped intrauterine device (IUD) enclosed by a non-porous membrane of ethylene-vinyl copolymer.
Ocusert system: In such a device, the solid drug reservoir, which is a thin disc of pilocarpine alginate, is sandwiched between two transparent sheets of microporous membrane fabricated from ethylene-vinyl acetate copolymer.
- Matrix diffusion-controlled drug delivery: In this mode of controlled drug delivery, the drug reservoir is formed by homogeneous dispersion of drug solid particles throughout a lipophylic or hydrophilic polymer matrix. The dispersion of drug solid particles in the polymer matrix can be accomplished by bending drug solids with a viscous liquid polymer or a semisolid polymer at room temperature, followed by crosslinking of polymer chains, or by mixing drug solids with a melted polymer at an elevated temperature. These drug polymer dispersions are then extruded to form drug delivery devices of various shapes and sizes. It can also be fabricated by dissolving the drug solid and/or the polymer in a common organic solvent followed by mixing and solvent evaporation in a mould at an elevated temperature and/or under a vacuum.
Eg. Contraceptive Vaginal Ring: It is fabricated by dispersing a contraceptive steroid, e.g., medroxyprogesterone acetate, as micronized solid particles in a viscous mixture of silicone elastomer and catalyst and then extruding the steroid-polymer dispersion into a mould to form a donut-shaped vaginal ring.
- Micro reservoir dissolution-controlled drug delivery: In this mode of controlled drug delivery, the drug reservoir, which is a suspension of drug crystals in an aqueous solution of a water miscible polymer, forms a homogeneous dispersion of millions of discrete, unleachable, microscopic drug reservoirs in a polymer matrix. The microdispersion is accomplished by high energy dispersion technique. Different shapes and sizes of drug delivery devices can then be fabricated from this microreservoir-type drug delivery system by moulding or extrusion technique.
B. Controlled drug release by activation:
- Osmotic pressure-activated drug delivery: In this mode of controlled drug delivery, the drug reservoir, which is a solution formulation, is contained within a semi-permeable housing. The drug is released in solution form a t controlled, constant rate under an osmotic pressure gradient.
Eg. 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 semipermeable polymer membrane.
- Vapour pressure activated drug delivery: In this mode of controlled drug delivery, the drug reservoir, in a solution formulation, is contained inside an infusate chamber, which is physically separated from the vapour chamber by a freely movable bellows. 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 cannula, into the blood circulation at a constant flow rate.
- Magnetism activated drug delivery: Macromolecular drugs, such a peptides, have been known to release only a relatively low rate from a polymeric drug delivery devices. This low release rate has been improved by incorporating a magnetism triggering mechanism into the polymeric drug delivery devices and a zero order drug release profile has also been achieved by a hemisphere shaped geometry design.
- 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, e.g., poly [bis(p-carboxyphenoxy) alkane anhydride].
- Hydrolysis activated drug delivery: This type of implantable therapeutic system is fabricated by dispersing a loading dose of solid drug, in micronized form, homogeneously throughout a polymer matrix made from bloerodible or blodegradable 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.
