Release system, controlled

A prolonged action/controlled release system developed to deUver levonorgestrel for contraceptive therapy involves implantation of a set of flexible closed capsules made of demethylsiloxane—methylvinyl—sdoxane copolymer (see Contraceptives). Each capsule measures 2.4 mm in diameter and 34 mm in length. A set of six such capsules is surgically implanted beneath the skin of the upper arm. These capsules are intended to be removed by the end of the fifth year after implantation. 

FIGURE 4 Controlled release systems based on lactide/glycolide polymers with duration of action of a few days to 1 year. 

Hsieh, D. S. T., Controlled Release Systems Fabrication Technology, Vol. 2, CRC Press, Boca Raton, 1988. 

Lewis, D. H., Tice, T. R., and Beck, L. R., Overview of controlled release systems for male contraception, in Male Contraception Advances and Future Prospects (G. I. Zatuchni, ed.). Harper and Row, Philadelphia, 1986, pp. 336-345. 

Bovine growth hormone, a difficult protein for which to develop controlled release systems due to its propensity toward self-aggregation and inactivation, has successfully been incorporated into polyanhydride matrices (18). The growth hormone was colyophilized with sucrose, dry-mixed with finely powdered polyanhydride, and then compression molded into 1.4-cm-diaraeter wafers, 1 mm thick. As is shown in Fig. 15, release of bovine growth hormone was well controlled over a prolonged period of time. The assay for bovine... 

Strobel, J. D., Laughlin, T. J., Austroy, F., Lilly, M. B., Perkins, B. H., and Dunn, R. L., Controlled-release systems for anticancer agents, Toronto Controlled Release Society, Proc. 14th Int. Symp. Control. Rel. Bioact. Materials. 261-262, 1987. 

Controlled release, although resulting in a zero-order delivery system, may also incorporate methods to promote localization of the drug at an active site. In some cases, a controlled-release system will not be sustaining, but will be concerned strictly with localization of the drug. Site-specific systems and targeted-delivery systems are the descriptive terms used to denote this type of delivery control. 

Historically, the oral route of administration has been used the most for both conventional and novel drug-delivery systems. There are many obvious reasons for this, not the least of which would include acceptance by the patient and ease of administration. The types of sustained- and controlled-release systems employed for oral administration include virtually every currently known theoretical mechanism for such application. This is because there is more flexibility in dosage design, since constraints, such as sterility and potential damage at the site of administration, axe minimized. Because of this, it is convenient to discuss the different types of dosage forms by using those developed for oral administration as initial examples. 

Since the left side of Eq. (7) represents the release rat of the system, a true controlled-release system with a zero-order release rate can be possible only if all of the variables on the right side of Eq. (7) remain constant. A constant effective area of diffusion, diffusional path length, concentration difference, and diffusion coefficient are required to obtain a release rate that is constant. These systems often fail to deliver at a constant rate, since it is especially difficult to maintain all these... 

Transdermal controlled-release systems can be used to deliver drugs with short biological half-lives and can maintain plasma levels of very potent drugs within a narrow therapeutic range for prolonged periods. Should problems occur with the system or a change in the status of the patient require modification of therapy, the system is readily accessible and easily removed. 

WR Good, KF Mueller. Hydrogels and controlled delivery. In SK Chandrasekaran, ed. Controlled Release Systems. AIChE Symp Ser 206. New York American Institute of Chemical Engineers, 1981, pp 42-51. 

Fig. 2. Schematic representation of the behavior of a one-dimensional swelling controlled release system. The water (W) penetrates the glassy polymer (P) to form a gel. The drug (D) is released through the swollen layer.

McCormick, C.L. and K.E. Savage, "Development of Controlled Release Systems Containing Pendant Metribuzin," Proceedings of the 1977 Controlled Release Symposium, pp. 28-40, Corvallis, Oregon (1977). 

To develop an HPLC stability-indicating method for Type I or II dissolution, the linearity must be wide enough, in combination with good sensitivity and minimal interference, to accommodate concentrations from low (possibly LOQ) to very high end, as the samples drawn represent the cumulative drug amount dissolved over time. As for an FiPLC method that is designed for Type VII dissolution, the linearity should accommodate the lower concentrations since it is a drug measurement of a controlled-release system. 

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