Examples of controlled release

Implantable devices:

Advantages include: Convenience, compliance, control and commercial, disadvantages surgery is need to be inserted/removed, possibility of failure, potency, reactions with body and commercial (time and money).

they can be used for pain, contraception, diabetes, incontinence, systemic infection, ocular and dental purposes. Contraceptives include rods, vaginal rings and IUD coil. Mirena is a diffusion-contolled DDS for local delivery and it is easily reversible. The coil is removed by pulling the strings of the device. Norplant and Jadelle (newer device where drug and matrix combined) rods involve 6 rods being implanted in the arm.

Intraocular delivery is also possible. Drug can be even inserted under sclera in the back of the eye. It is unpleasant to insert an implant in the eye, but is better than injections. RESISERT (diffusion-controlled delivery) was the first CR device for eye delivery and is used to treat chronic noninfectious uveitis lasts for 30months before removed by taking off the sutures and decreases chances of reoccurance of uveitis. The matrix device has a drug core and a polyvinyl membrane. IVATION INTRAVETREAL IMPLANT (diffusion-controlled DSS) is used for AMD, DME and glaucoma. It looks like a screw, but is tiny compared to a coin. It consists up an erodible polymer and it can stay in the sub-conjuctiva of the eye for around 2 years. MEDIDUR is an device which is injected/dropped at the back of the eye and replaced after 36months, but is currently under phase III clinical trials, VITRASERT lasts for 5-8months and OCUSERT is a device used once weekly instead of 28drops squeezed in the eye.

There is also a Pressure-responsive Intraocular implantable delivery device which works by electronically-controlled pump. It is inserted in the conjuctiva and a reservoir contains the drug. When neccesary an injection of drug is being done to refill the reservoir. The advantage is that instead of injecting the eye, the device is being punched. The device then self-heals and release the drug by repsonding to mechanical force.

Drug-eluting stents (diffusion or chemically controlled release) which is an artificial 'tube' inserted into a natural passage/conduit in the body to prevent, or counteract, a disease-induced, localized flow constriction (stenosis of blood vessels). Restenosis (amount of cells reinfiltered after stent loss) limits effectiveniness though. Used to deliver cytotoxic drug such as Paciltaxel.

Examples of osmotic delivery devices include: DUROS, a catheter direct drug specifically to 1 point protected by body all time. The drug is pushed out of the orifices by a semi-permeable membrane.

Examples of degradable devices include: DURIN (chemically-controlled DDS, drug and rate-limiting polymer mixed into fibre, rod or tablet), GLIADEL wafers used in the treatment of malignant gliomas.

Mechanical pumps are also available. An example is the one to control insulin release. It monitors glucose, transmits reading to pump and secrete insulin. There is also an implantable pump controlled by the phycisian. It is implanted every 3 months and contains 6000units of insulin. However, if pump fails, it will cause trouble to patients.

There are also mechanical pumps for intrathecal delivery for severe chronic tumour pain management with morphine sulphate.

Lastly, in the future, Micro-scale delivery will be feasible. In a microfibrated osmotic engine, water flow increases and pushes balloon upwards to the hole to be released and delivered to patients. Osmotic agent pushes drug dwon. The size of the device is tiny with V capacity of microL, so drug needs to be potent!

Controlled release microchip: a metal mould with conical holds with sealing top with erodible. Underneath insoluble polymer sealing. Only way drug escape is through top. Each hole can be filled with different polymers to give a pulsatile effect. It works via erosion and PLGA tailors the rate of erosion, by changing the lactic acid, hydrophobicity and MR (methyl groups) is increased, making it harder to degrade as opposed to the hydrophilic glycolic acid.