Controlled release drug delivery systems requirements

Another circumstance in which there may be generally compelling reasons to require quantification of active metabolites is when a controlled-release drug-delivery system is used for a drug that has an active metabolite. Some of the papers that consider the topics of bioequivalency testing for drugs with long half-lives or active metabolites are listed in the references section of this chapter [12-17]. 

Drug Delivery System To develop a viable oral controlled-release drug delivery system capable of delivering a drug at a therapeutically effective rate to a desirable site for the duration required for optimal efficacy. 

When the transdermal penetration of a drug is inadequate to achieve and maintain a plasma concentration above the minimum therapeutic concentration required to produce the desired effect, a lipophilic prodrug that will be metabolized in the epidermis to the active drug could be used in the development of a controlled-release transdermal delivery system. This approach has been applied to estradiol esters (diacetate and valerate) which are rapidly converted by esterases in the skin tissue to estradiol (Chien et al, 1985). The prodrug serves to increase the transdermal bioavailability of the active drug to which it is converted by metabolism (generally ester hydrolysis) during the percutaneous absorption process. 

Major barriers to the use of conventional vesicles in many applications include (1) the inherent long-term instability of the systems, (2) their potential for interaction with enzymes and blood lipoproteins, and (3) their susceptibility to the actions of other surface-active materials. For such critical applications as controlled-release drug delivery, even the most stable systems with a lifetime of several months do not begin to approach the shelf life requirements. 

Chitosan was also formulated in a controlled-release protein delivery system using bovine serum albumin (BSA) as a model drug. Chitosan was reacted with sodium alginate in the presence of tripolyphosphate for bead formation [94]. Parenteral administration of proteins/peptides requires repeated injections because of their extremely short biological half-life. Daily multiple injections are highly risky and require close medical supervision. On this basis, bovine serum albumin (BSA)-loaded chitosan microspheres were prepared to test the drug release behavior in buffers with different pH values. BSA-chitosan microspheres with particle sizes in the range from 5 to 10 pm... 

E. Lipka and G. L. Amidon, Setting bioequivalence requirements for drug development based on preclinical data optimizing oral drug delivery systems, J. Controlled Release, 62, 41 (1999). 

Siepmann J, Lecomte F, Bodmeier R. Diffusion-controlled drug delivery systems calculation of the required composition to achieve desired release profiles. / Control Release 1999 60(2-3) 379-389. 

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