Solution-diffusion mechanism, drug release

The rate controlling membranes in encapsulated drug devices are most commonly made of dense polymeric materials. In these devices, a solution-diffusion mechanism controls release rates. Pick s First Law governs the specific release rate (q) ... 

Single Component System. In a single component system, the drug is encapsulated in its pure form and release rates are essentially zero order (72). Polydimethylsiloxane and polyethylene are the materials most often chosen for encapsulation. Table HI shows some typical release rates reported by Kind, et al. (14), for various steroids through silicone rubber. Clearly, when a solution-diffusion mechanism controls the drug release rate, drug permeabilities can be expected to vary widely. 

The effect of various chemical modifications on the mechanical properties of reconstituted collagen and the diffusion rates of the steroid medroxyprogesterone was investigated (38). Formaldehyde-treated films, which are heavily crosslinked, have high moduli and low rates of drug release. Films treated with chrome quickly become hydrated in solution and have low moduli and very rapid drug release characteristics. 

The release from microcap systems is more complicated. First the drug has to dissolve in dissolution fluid which has diffused into the tablets via pores and then between the plates of poly (DL-lactic acid) forming the walls of the microcapsules. This drug solution then has to diffuse out of the tablet via the same route. The effect of compression on the release has more significance in the simple matrix tablets than the microcap systems, because of the above mechanism of release. Higher compressions reduce the size of the pores between the poly(DL-lactic acid) plates, which extends the release. 

The mechanism of drug release from hydrophilic matrix tablets after ingestion is complex but it is based on diffusion of the drug through, and erosion of, the outer hydrated polymer on the surface of the matrix. Typically, when the matrix tablet is exposed to an aqueous solution or gastrointestinal fluids, the surface of the tablet is wetted and the polymer hydrates to form a gelly-like structure around the matrix, which is referred to as the gel layer . This process is also termed as the... 

Peppas, L. B. Peppas, N. A. Solute and penetrants diffusion in swellable polymers IX. The mechanisms of drug release from pH-sensitive sweUing controlled systems. J. Controlled Release 1989, 8, 267-274. 

One of the possible solutions to this problem is to use a system of controlled drug delivery in which the drug is released at a constant, preset rate, preferably close to the specific location. One of the most notable approaches is when the drug is contained in a polymer membrane (or encapsulated in a polymer matrix), from which it diffuses out into the tissue in which the membrane/matrix is implanted. In some cases the mechanism of drug release is affected by erosion or polymer dissolution. Degradable polymers such as poly(lactic acid) or polyorthoesters can be used for drug delivery systems of this type [57, 58]. 

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