Eroding systems

Computer simulation of eroding matrices (Fig. 8.36) can give an accurate representation of the process and can predict the position of the erosion front and the weight of the matrix. 

More precise control of release than is possible with matrices has recently been achieved by the application of several features of polymer physical chemistry, as discussed below. 

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Fig. 6. Mechanism of drug release from (a) homogenous, surface-eroding system, and...

An alternative system, manufactured as a wafer-like insoluble implant, has been developed (Ocusert). The system is preprogrammed to release pilocarpine at a constant rate of 20 or 40 / g/hr for a week to treat chronic glaucoma however, release from inserts may be incomplete and approximately 20% of all patients treated with the Ocusert lose the device without being aware of the loss. The device also presents problems including foreign-body sensation, expulsion from the eye, and difficulty in handling and insertion. An alternative to the advanced non-erodible systems is an erodible insert for placement in the cul-de-sac. 

Fig. 5 Eroding system with hollow cylinder and coated surfaces. (From Ref. f)...

To be useful as an implant, the polymer must hydrolyze to small, water soluble and toxicologically safe molecules and to be useful as a surface-eroding system, the hydrolysis must occur at much higher rates in the outer layers than it does in the bulk. Therefore, the successful development of such devices requires the selection of bonds that are capable of undergoing rapid hydrolysis. Two such bonds are anhydrides which are rapidly hydrolyzed to diacids even at the physiological pH of 7.4 and ortho esters which at pH 7.4 are slow to hydrolyze but which hydrolyze at increasingly rapid rates as the pH is lowered. Polymers based on both of these linkages are under intensive development and this chapter will cover, in depth, the development and current status of poly (ortho esters). 

The synchronization of the two fronts is rapidly achieved with PVAL and soon produces a zero-order release. In the system containing HPMC, the synchronization is still not reached when, at approximately 300 min, the swelling front stops. Nevertheless, from that moment, drug release is constant because the system behaves as a conventional erodible system. 

The enhanced release was also observed in non-erodible systems exposed to ultrasound where the release is diffusion dependent. This was tested on EVAc copolymers loaded with BSA or insulin. The released insulin was also evaluated by HPLC. No significant difference was detected between insulin samples exposed to ultrasound and unexposed samples, suggesting that the ultrasound is not degrading the releasing molecules. 

Experiments were also performed to evaluate whether the extent of enhancement could be regulated externally. By varying the ultrasound intensity, the degree of enhancement for both polymer degradation and drug release for the bioerodible and non-erodible systems could be altered 10-fold (42). 

Figure 18.18 Drug delivery from biodegradable systems, (A) surface eroding biodegradable system, (B) bulk eroding system [38].

Chemically controlled release is governed by reactions that occur within polymer systems. In chemically controlled erodible systems, the drag release rate is controlled by degradation or dissolution of the polymer. In contrast to this, in pendent chain systems cleavage of polymer chains between the polymer network and a drag occurs via hydrolytic or enzymatic degradation (Peppas et al., 2000). 

The area of applied bioactive polymeric systems includes such diverse entities as controlled release systems (erodable systems, diffusion controlled systems, mechanical systems and microcapsules), and biologically active polymers, such as natural polymers, synthetic polypeptides, pseudo-enzymes, pseudo-nucleic acids and polymeric drugs. The area can also include immobilized bioactive materials, such as immobilized enzymes, antibodies and other bioactive agents and the area of artificial cells. This Chapter reviews the general field of biologically active synthetic and modified natural macromolecules with an emphasis on their common characteristics, problems and applications. The areas reviewed include both medical and non-medical applications for both controlled release systems and polymers that exhibit direct biological activity. 

The basic concepts of controlled release systems will be considered below under the headings (a) erodable systems, (b) diffusion controlled... 

An erodable system contains the biologically active agent within some polymeric system which will dissolve or be destroyed by the biological media in which it is placed. Among the oldest medical examples are the... 

In spite of the non-achievement of front movement synchronization, when such systems are needed In pharmaceutical applications constant drug release has been observed at later times, i.e. when the swelling front is no longer active. The systems behave from that moment on as classical erodible systems with synchronization of the diffusing and eroding fronts (Figure 8). 

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