Dissolution drug delivery devices

Figure 3. In vitro delivery of diclofenac sodium from a buccal drug delivery device (details of the dissolution method are given in the text). ...

Fyfe CA, Grondey H, Blazek-Welsh Al, et al. NMR imaging investigations of drug delivery devices using a flow-through USP dissolution apparatus. J Control Release 2000 68(l) 73-83. 

Stimulation of saliva production is under sympathetic and parasympathetic control. Parasympathetic stimulation produces a serous watery secretion, whereas sympathetic stimulation produces much thicker saliva. Drug delivery systems, therefore, should not be placed over a duct or adjacent to a salivary duct, as this may dislodge the retentive system or may result in excessive wash-out of the drug or rapid dissolution/erosion of the delivery system making it difficult to achieve high local drug concentrations. If a retentive system is placed over salivary ducts, the reduced salivary flow rate may produce less or no mucus which is required for the proper attachment of a mucoadhesive delivery device. 

Solid oral dosage forms containing new chemical entities (NCEs) are commonly formulated into tablets or capsules as their first market image formulation. Subsequent drug product line extension development on these NCEs may evaluate more specialized drug delivery systems. Dissolution testing of standard oral tablets or capsules will commonly utilize the paddle or basket apparatus. In this chapter we focus primarily on the development and subsequent validation of dissolution testing methods that use these two devices. 

Heller, J., and Trescony, P. Controlled drug release by polymer dissolution 11. Enzyme-mediated delivery device. J. Pharm. Sci. 68 919—921, 1979. 

In bioerodible drug delivery systems various physicochemical processes take place upon contact of the device with the release medium. Apart from the classical physical mass transport phenomena (water imbibition into the system, drug dissolution, diffusion of the drug, creation of water-filled pores) chemical reactions (polymer degradation, breakdown of the polymeric structure once the system becomes unstable upon erosion) occur during drug release. 

Figure 3. Microfluidic Device. (A) Time lapse illustrating repulsion the ejection of 1.9 pm fluorescent polystyrene microsphere particles from an electroactive microwell. After dissolution of the membrane, the fluorescent particles can be seen in the well. White hnes outline the gold electrodes features. Images are taken every 2 s (total of 10 s). (B) Schematic of the electroactive microwell drug delivery system developed here. Scale bar represents 2 mm. (C) Micro fluidic device with electrical leads connected to thin copper wires. Inset Magnified view of microchip from above looking at the region near the membrane. (D) To illustrate the electrokinetic transport processes involved in the ejection stage, a finite element analysis of time-dependent species transport of the system is shown. Images show cut view of species concentration every 60 s up to 300 s after the ejection process.

In vitro and in vivo biocompatibUity tests are required by government agencies for drug delivery system and biomedical device approval [16]. In vitro dissolution testing is used to assess in vivo performance and is important during formulation development as weU as for product quality assurance. Standardized dissolution methods are under development for novel polymeric formulations such as microspheres, nanoparticles, and in situ forming gels [17]. 

It is safe to assume that for a given dissolution device, the ultimate drug delivery rate will be a combination of hydrolysis (dissolution) and drug diffusion out of the polymer. Of the systems stuped to date, the release rates for biodegradable devices are essentially zero-order. 

Another facet of parenteral drug delivery is the implanted device, and this is perhaps the most promising and most readily commercialised area for responsive and/or active polymers. For an implanted vehicle or depot, drag release rate is controlled by dissolution and/or diffusion in the formulation, or for solid polymer implants by diffusion and/or degradation of the polymer. For more complex polymer hydrogels, the release can be controlled by the linking chemistries, and these can be made responsive to a wide variety of stimuli such as enzymatic action, redox potential and so on, as well as those noted above for the oral route. 

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