Controlled release approaches

Figure 23. Scheme of biodegradeable controlled release approaches. 

The purpose of this paper is to give illustrative examples of the controlled-release approach, and to discuss the principles and the challenges of this promising technology. The following examples are based on studies conducted in our laboratories. 

One typical example of a controlled-release approach is the Smartamine system for ruminants developed and commercialized by Rhone-Poulenc Animal Nutrition. Smartamine products are rumen-protected amino-acids which are added to the feed of dairy cows in order to increase the protein content of the milk. 

A more constructive approach to nuclear fusion—one that achieves a controlled release of nuclear energy—is to heat a plasma, or ionized gas, by passing an electric current through it. The very fast ions in the plasma are kept away from the walls of the container with magnetic fields. This method of achieving fusion is the subject of intense research and is beginning to show signs of success (Fig. 17.27). 

For many drug delivery applications, the preferred method of delivery of the dosage form is by injection. For controlled release applications, the most frequently used approach to allow this method of administration is to prepare microspheres of the polymer containing the drug to be delivered. Several different techniques have been developed for the preparation of microspheres from polyanhydrides. 

Kohn, J., and Langer, R., A new approach to the development of bioerodible polymers for controlled release applications employing naturally occurring amino acids, in Proceeding of the ACS Division of Polymeric Materials. Science and Engineering. American Chemical Society, 1984, Vol. 51, pp. 119-121. 

A different approach reported recently (30) involves the synthesis and evaluation of polyphosphazenes that contain both aryloxy and imldazolyl side groups. Hydrolytic removal of the imidazolyl units takes place with a concurrent erosion of the solid polymer in a manner that is appropriate for the controlled release of entrapped drug molecules. 

L-C Dong, AS Hoffman. A novel approach for preparation of pH-sensitive hydrogels for enteric drug delivery. J Controlled Release 15 141-152, 1991. 

Yang J, Yamato M, Nishida K, Ohki T, Kanzaki M, Sekine H, Shimizu T, Okano T (2006) Cell delivery in regenerative medicine the cell sheet engineering approach. J Control Release 116 193-203. 

Hamalainen KM, Kontturi K, Auriola S, Murtomaki L, Urtti A. Estimation of pore size and pore density of biomembranes from permeability measurements of polyethylene glycols using an effusion-like approach. J Control Release 49 97-104 (1997). 

Sonication using ultrasonic cleaner baths remains a popular extraction approach particularly for controlled-release products. In sonication, an ultrasonic wave of 20-40 kHz generated by a piezoelectric transducer is used to produce the formation and collapse of thousands of microscopic bubbles (cavitations) in the water bath to facilitate the break up of the solid particles and the subsequent dissolution of the API. Note that parameters such as the wattage power of the sonicator, presence of the perforated tray, depth of the water level, bath temperature and the number of sample flasks sonicated might all affect the extraction rate. For... 

But even a small-scale trial-and-error strategy has to be organised within society. As discussed in the previous section, iimovations are rather improbable and disadvantaged by stractural frameworks. Iimovations depend upon freedom for them to be developed. At the same time safety barriers have to be formulated within which the search process can move freely. For example, possible environmental effects must be anticipated, necessitating controlled release in small increments and retrievability must be ensured. (Quantitative and qualitative restrictions must be imposed so that retrieval and repair options can still be effective if a trial is aborted. This approach is more successful if the persistence and spatial range of a chemical is low than for persistent chemicals like CFCs and PCBs. This requires that limited Teaming spaces or experimentation spaces have to be created intentionally under technical and economic risk considerations. Small increments and a steady increase are to be preferred, accompanied by intensive monitoring of detectable consequences. 

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