Injectable implant drug delivery system

Pharmaceutically viable formulation applications include topical, pulmonary, depot and implantable drug delivery systems (Bhardwaj and Blanchard, 1996 Cleland andjones, 1996 Schwendeman etal., 1996 Johnsonetal., 1997 Schwendeman et al., 1997 Carrasquillo et al., 1999 Stevenson et al., 1999 Wright et al., 2001 Kikwai et al., 2004). Simple depot formulations, designed to decrease dissolution rates, have used non-aqueous conditions to achieve controlled release. Growth hormone has also been suspended in oil for depot injections (Yu et al., 1996). 

The Norplant device has been somewhat controversial, however, due to difficulties associated with its removal. A second example of an implantable drug delivery system is Zoladex, which is an implantable biodegradable lactide/glycolide polymeric delivery system for the administration of goserelin acetate. It is available in one-month and three-month presentations and can be injected through a wide-bore needle. 

Implantable drug delivery systems are defined as longterm (>30 days) implantable products that are resorbable or removable. The resorbable implants are injectables incorporating lyophilized microspheres. The removable version is typically a subcutaneous implant, requiring minor outpatient procedures for insertion and removal. The main commercialized product in this category is Norplant , a contraceptive implant. Medtronic Corporation has two products in the implantable area that allow drug delivery into the intrathecal space (where the spinal fluid circulates). One of these products delivers baclofen for spasticity, and the other delivers anaesthetics for pain control. Both products utilize Medtronic s SynchroMed infusion pump, which can be electronically programmed to deliver any type of preset dose. 

Materials that gel in situ have recently gained attention as promising implantable drug delivery systems as well as injectable matrices for tissue engineering (76). 

Silicon micropumps offer major advantages in terms of system miniaturization and control over low flow rates with a stroke volume 160 nL.14 The micropump has the characteristics of very small in size, implantability in the human body, low flow rates (in the range of 10 pL/min), moderate pressure generation from the microactuator to move the drug, biocompatibility, and most important, a reliable design for safe operation. The implantable device is particularly suitable (over the injectable drug delivery systems) for patients with Parkinson s disease, Alzhiemer s disease, diabetes, and cancer, as well as chronically ill patients, because the catheter that is attached to the device can transport drug to the required site. 

Figure 2.3 IgG levels after administration of drug delivery systems in rats. Controlled-delivery systems for antibody class IgG. The insert figures show the release of antibody from the delivery system during incubation in buffered saline. The panel (a) inset shows release from poly(lactic acid) microspheres these spherical particles were 10-100/rm in diameter. The panel (b) inset shows release from a poly[ethylene-co-(vinyl acetate)] matrix these disk-shaped matrices were 1 cm in diameter and 1 mm thick. In both cases, molecules of IgG were dispersed throughout the solid polymer phase. Although the amount of IgG released during the initial 1-2 days is greater for the matrix, the delivery systems have released comparable amounts after day 5. (a) Comparison of plasma IgG levels after direct injection of IgG (open circles) or subcutaneous injection of the IgG-releasing polymeric microspheres characterized in the inset (filled circles). The delivery system produces sustained IgG concentrations in the blood [3]. (b) Comparison of plasma IgG levels after direct intracranial injection of IgG (open squares) or implantation of an IgG-releasing matrix (filled squares) [4]. The influence of the delivery is less dramatic in this situation, probably because the rate of IgG movement from the brain into the plasma controls the kinetics of the overall process.

The applications of hydrogels in the production of medical items, resulting materials must have several features, which recommends them non-toxicity, functionability, sterilizability, biocompatibUity [115]. These characteristics are requires for wound dressings, drug delivery systems, transdermal systems, injectable polymers, implants, dental and ophthalmic applications, stimuli-responsive systems, hydrogel hybrid-type organs. 

When active substances are encapsulated in drug delivery systems, their bioavailability and therapeutic index can be improved over an extended period of time. A drug delivery system including polymer microspheres has been developed for injection, implants, transdermal patches, and aerosols (34). 

The lactide/glycolide bioresorbable polymers are thermoplastics which can be processed by many methods, including fibre spinning, extrusion, and injection moulding, which means they can be fabricated into a variety of wound closure items (e.g. sutures), implantable devices (e.g. bone plates, bone screws), and drug delivery systems, which include microspheres, fibres, films, rods and others. 

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