A. Controlled Drug Release by Diffusion:
1. 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 solid drug particles or a dispersion (or a solution) of solid drug particles in a liquid - or a micro porous (or a semi permeable) membrane. The encapsulation of drug reservoir inside the polymeric membrane can be accomplished by molding, capsulation, micro encapsulation, or other techniques. Different shapes and sizes of drug delivery devices can be fabricated.
Representatives of this type of implantable therapeutic systems are Progestasert IUD and occusert system already discussed in Part I of the article.
2. Matrix Diffusion-Controlled Drug Delivery :
In this mode of controlled drug delivery, the drug reservoir is formed by homogeneous dispersion of solid drug particles throughout a lipophilic or hydrophilic polymer.
The dispersion of solid drug particles in the polymer matrix can be accomplished by blending solid drugs with a viscous liquid polymer or a semisolid polymer at room temperature, followed by cross linking of polymer chains, or by mixing solid drugs 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 solid drug and / or the polymer in a common organic solvent followed by mixing and solvent evaporation in a mould at elevated temperature and / or under vacuum which defines the flux of drug release at a steady state from a matrix diffusion-controlled drug delivery device.
Representative of this type of implantable therapeutic system are:
a) 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 vaginal ring. It is designed to be inserted into the vagina and positioned around the cervix for 21 days to achieve a constant plasma progestin level and cyclic intravaginal contraception.
b) Syncro-Mate-B Implant
It is fabricated by dissolving norgestomet crystals in an alcoholic solution of ethylene glycomethacrylate (Hydron S) and then polymerizing the drug-polymer mixture by the addition of a cross linking agent, such as ethylene dimethacrylate, and an oxidizing catalyst to form a cylinder-shaped insoluble Hydron implant. This tiny subdermal implant is engineered to be inserted into the subcutaneous tissue, using a specially designed implanter to release norgestomet at a rate of 504 mcg/cm2 /day1/2 for up to 16 days for estrus control and synchronization in livestock.
c) Compusode Implant
It is fabricated by dispersing micronized estradiol crystals in a viscous mixture of silicone elastomer and catalyst and then coating the estradiol-polymer dispersion around a rigid silicone rod by extrusion technique to form a cylinder-shaped implant. This subdermal implant is designed for subcutaneous ear implantation. It steers for 200 to 400 days and to release a controlled quantity of estradiol for growth promotion. In the next post, we shall discuss further on this topic of different rate controlling parameters for implant delivery systems.
3. Microreservoir 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 reservoir in a polymer matrix. The micro dispersion is accomplished by high-energy dispersion technique.
Different shapes and sizes of drug delivery devices can then be fabricated from this micro reservoir-type drug delivery system by molding or extrusion technique. Depending upon the physicochemical properties of drugs and the desired rate of drug release, the device can be further coated with a layer of biocompatible polymer to modify the mechanism and the rate of drug release.
Representatives of this type of drug delivery devices are: -
a) Syncro-Mat-C Implant
It is a cylindrical implant with improvement in both release rate profile and cost saving over the Syncro-Mate-B implant discussed earlier. It is fabricated by dispersing the drug reservoir, which is a suspension of norgestomet in an aqueous solution of PEG 400, to form millions of microscopic drug reservoirs in a viscous mixture of silicone elastomers by high-energy dispersion technique.
After the addition of catalyst, the resultant composition is delivered into a silicone medical-grade tubing, which serves as the mould as well as the coating membrane, by extrusion technique and is polymerized in situ. The polymerized solid drug-polymer composition is then cut into cylinder-shaped drug delivery device with open ends.
This tiny subdermal implant is designed to be inserted, by a specially designed implanter, and to deliver norgestomet in the subcutaneous tissue in livestock’s earflap for up to 20 days for the control and synchronization of estrus and ovulation.
b) Dua-Release Vaginal Contraceptive Ring
It is fabricated by dispersing the drug reservoir, which is a suspension of a progestin and an estrogen in an aqueous solution of PEG 400, to form many microscopic drug reservoirs in a viscous mixture of silicone elastomers by high-energy mixing technique.
After addition of catalyst, the resultant composition is extruded into a mould, by extrusion technique, and is polymerized by heat to form a donut-shaped vaginal ring. It is designed to permit the user to insert the ring themselves and to release both progestin and estrogen, at a specific rate ratio, in the vagina for 21 days to achieve a cyclic intravaginal contraception.
1. 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 solid drug particles or a dispersion (or a solution) of solid drug particles in a liquid - or a micro porous (or a semi permeable) membrane. The encapsulation of drug reservoir inside the polymeric membrane can be accomplished by molding, capsulation, micro encapsulation, or other techniques. Different shapes and sizes of drug delivery devices can be fabricated.
Representatives of this type of implantable therapeutic systems are Progestasert IUD and occusert system already discussed in Part I of the article.
2. Matrix Diffusion-Controlled Drug Delivery :
In this mode of controlled drug delivery, the drug reservoir is formed by homogeneous dispersion of solid drug particles throughout a lipophilic or hydrophilic polymer.
The dispersion of solid drug particles in the polymer matrix can be accomplished by blending solid drugs with a viscous liquid polymer or a semisolid polymer at room temperature, followed by cross linking of polymer chains, or by mixing solid drugs 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 solid drug and / or the polymer in a common organic solvent followed by mixing and solvent evaporation in a mould at elevated temperature and / or under vacuum which defines the flux of drug release at a steady state from a matrix diffusion-controlled drug delivery device.
Representative of this type of implantable therapeutic system are:
a) 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 vaginal ring. It is designed to be inserted into the vagina and positioned around the cervix for 21 days to achieve a constant plasma progestin level and cyclic intravaginal contraception.
b) Syncro-Mate-B Implant
It is fabricated by dissolving norgestomet crystals in an alcoholic solution of ethylene glycomethacrylate (Hydron S) and then polymerizing the drug-polymer mixture by the addition of a cross linking agent, such as ethylene dimethacrylate, and an oxidizing catalyst to form a cylinder-shaped insoluble Hydron implant. This tiny subdermal implant is engineered to be inserted into the subcutaneous tissue, using a specially designed implanter to release norgestomet at a rate of 504 mcg/cm2 /day1/2 for up to 16 days for estrus control and synchronization in livestock.
c) Compusode Implant
It is fabricated by dispersing micronized estradiol crystals in a viscous mixture of silicone elastomer and catalyst and then coating the estradiol-polymer dispersion around a rigid silicone rod by extrusion technique to form a cylinder-shaped implant. This subdermal implant is designed for subcutaneous ear implantation. It steers for 200 to 400 days and to release a controlled quantity of estradiol for growth promotion. In the next post, we shall discuss further on this topic of different rate controlling parameters for implant delivery systems.
3. Microreservoir 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 reservoir in a polymer matrix. The micro dispersion is accomplished by high-energy dispersion technique.
Different shapes and sizes of drug delivery devices can then be fabricated from this micro reservoir-type drug delivery system by molding or extrusion technique. Depending upon the physicochemical properties of drugs and the desired rate of drug release, the device can be further coated with a layer of biocompatible polymer to modify the mechanism and the rate of drug release.
Representatives of this type of drug delivery devices are: -
a) Syncro-Mat-C Implant
It is a cylindrical implant with improvement in both release rate profile and cost saving over the Syncro-Mate-B implant discussed earlier. It is fabricated by dispersing the drug reservoir, which is a suspension of norgestomet in an aqueous solution of PEG 400, to form millions of microscopic drug reservoirs in a viscous mixture of silicone elastomers by high-energy dispersion technique.
After the addition of catalyst, the resultant composition is delivered into a silicone medical-grade tubing, which serves as the mould as well as the coating membrane, by extrusion technique and is polymerized in situ. The polymerized solid drug-polymer composition is then cut into cylinder-shaped drug delivery device with open ends.
This tiny subdermal implant is designed to be inserted, by a specially designed implanter, and to deliver norgestomet in the subcutaneous tissue in livestock’s earflap for up to 20 days for the control and synchronization of estrus and ovulation.
b) Dua-Release Vaginal Contraceptive Ring
It is fabricated by dispersing the drug reservoir, which is a suspension of a progestin and an estrogen in an aqueous solution of PEG 400, to form many microscopic drug reservoirs in a viscous mixture of silicone elastomers by high-energy mixing technique.
After addition of catalyst, the resultant composition is extruded into a mould, by extrusion technique, and is polymerized by heat to form a donut-shaped vaginal ring. It is designed to permit the user to insert the ring themselves and to release both progestin and estrogen, at a specific rate ratio, in the vagina for 21 days to achieve a cyclic intravaginal contraception.
