Injectable Drug Delivery Systems

An example of such a product is Sterile Medroxyprogestrone Acetate Suspension used for its contraceptive property. Such an injection is designed to provide up to three months of contraceptive activity. Another such product is a depot injection of leuprolode acetate, an analogue of gonadatropin-releasing hormone (see Drug delivery systems). In this case, the product is a sterilized powder of microspheres to be suspended upon the addition of an appropriate diluent and intended for monthly injection. 

L Eith, RFT Stepto, F Wittwer, I Tomka. Injection-moulded drug-delivery systems. Manuf Chem 58(1) 21, 1987. 

Jeong B, Choi YK, Bae YH et al (1999) New biodegradable polymers for injectable drug delivery systems. J Control Release 62 109-114... 

Gray, J.E. (1978). Pathological evaluation of injection injury. In Sustained and Controlled Release Drug Delivery Systems (Robinson, J., Ed.). Marcel Dekker, New York, pp. 351-405. 

Drug-delivery systems are essentially specialized dosage forms developed to overcome the limitations of conventional dosage forms, such as simple tablets, capsules, injectable solutions, etc. Some of the reasons behind the development of oral DDSs are listed below ... 

A composition based on diketopiperazine derivatives (3,6-bis (N-fumaryl-N-(n-butyl) amino-2, 5-diketopiperazine) has been investigated as a pulmonary drug delivery system, termed Technospheres (Pharmaceutical Discovery Corp., Elmsford, NY) (Pohl et al. 2000 Steiner et al. 2002). The diketopiperazine derivatives self-assemble into microparticles at low pH with a mean diameter of approximately 2 pm. During self-assembly, diketopiperazine derivatives microencapsulate peptides present in the solution. Insulin incorporated in diketopiperazine derivatives (TI) was administered to five healthy humans by the use of a capsule-based inhaler with a passive powder deagglomeration mechanism. Relative and absolute bioavailability of TI in the first 3 hours (0-180 min) were 26 12% and 15 5%, and for 6 hours (0-360 min) 16 8% and 16 6%, respectively (Steiner et al. 2002). The time to peak action for glucose infusion rates was shorter with both IV (14 6 min) injection and inhalation (39 36 min), as compared to SC administration (163 25 min). This rapid absorption of insulin would be beneficial for diabetic patients who need to rapidly affect their glucose levels. 

One of the main drivers for the development of new pulmonary drug delivery systems has been the potential for noninvasive systemic delivery of protein and peptide compounds. The systemic delivery of macromolecules via the airways would overcome the inconvenience and cost associated with current methods of administration (injection), and appears likely given the large surface area of the airways and the thin pulmonary epithelium. Most research has concentrated on pulmonary delivery of insulin for the treatment of diabetes. Recently, one insulin product has completed phase three studies and is now undergoing review by European regulatory agencies for marketing approval. 

Conventional liposomes and lipid complexes. Liposomes were used initially as a model system for cellular membranes to study the biochemistry of membrane proteins.85 Consequently, when liposomes were first tried as a drug delivery system, their bilayers were composed of un-derivatized naturally occurring lipids. Most of such conventional liposomes are taken up by the MPS phagocytes within a few hours of injection, mostly by liver Kupffer cells and spleen macrophages.9 Inside the endosomes and lysosomes of those cells, liposomes are degraded. If the liposomal drugs are membrane permeable, they then can diffuse from the endosomal compartments to the cytoplasm of the macrophage cells and slowly reenter the blood circulation. Because such a clearance... 

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. 

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