Dissolution-controlled systems

Microreservoir dissolution-controlled system in which microscopic spheres of drug reservoir are dispersed in a polymer matrix Nitrodisc (nitroglycerin Searle). 

For water-insoluble drugs, dissolution-controlled systems are an obvious choice for achieving sustained-release because of theirslow dissolution rate characteristics. Theoretically, the dissolution process at steady state can be described by the Noyes-Whitney equation as shown in Equation 22.7. The rate of dissolution of a compound is a function of surface area, saturation solubility, and diffusion layer thickness. Therefore, the rate of drug release can be manipulated by changing these parameter. 

In addition, such semicrystalline materials of PVA were further examined in some rather unique ways by Mallapragada et al. [89, 90]. Specifically, the crystal dissolution-controlled system described was investigated for the controlled release of metronidazole [89]. The crystalline phase of this system was also characterized more closely in terms of modifications of drug-release profiles [90],... 

Peppas, N. A., A model of dissolution-controlled solute release from porous drug delivery polymeric system, J. Biomed. Mater. Res., 17. 1079, 1983. 

Because of their relative ease of production and cost compared with other methods of sustained or controlled delivery, dissolution and diffusion-controlled systems have classically been of primary importance in oral delivery of medication. Dissolution systems have been some of the oldest and most successful oral systems in early attempts to market sustaining products. 

Fig. 2 Two types of dissolution-controlled, pulsed delivery systems (A) single bead-type device with alternating drug and rate-controlling layers (B) beads containing drug with differing thickness of dissolving coats.

The diffusivity, D, of the dissolved solute, if dissolution is transport-controlled (Eqs. 41-46,49,51,52). The dissolution rate of a reaction-controlled system will be independent of D. 

Dissolution, of viscose, 11 254-255 Dissolution-controlled drug delivery, degradation/ erosion-based drug delivery systems, 9 11-19 Dissolution inhibition, by... 

Various dissolution test systems have been developed and several of them now enjoy compendial status in pharmacopeias, for example the reciprocating cylinder (United States Pharmacopeia Apparatus 3), the flow-through apparatus [European Pharmacopoeia (Pharm. Eur.) 2.9.3], or the apparatus for transdermal delivery systems, such as the paddle over disc. Hydrodynamic properties of these and other apparatus have been described only sparingly. The paucity of quantitative data related to hydrodynamics of pharmacopeial dissolution testers is lamentable, since well-controllable hydrodynamics are essential to both biopharmaceutical simulations and quality control. Here, we focus the discussion on the paddle and the basket apparatus, since these are the most important and widely used for oral solid dosage forms. A brief treatise on the hydrodynamics of the flow-through apparatus completes this section. 

Another important consequence of the constant rate of release diffusion model is that it mimics many of the features that have commonly been attributed to surface reaction (matrix dissolution) control. If one were to account for changes in surface area over time, the predicted long-term dissolution rate due to surface reaction control would also yield constant element release. In surface reaction controlled models, the invariant release rate with respect to time is considered to be the natural consequence of the system achieving steady-state conditions. Other features of experiments commonly cited as evidence for surface reaction control, such as relatively high experimental activation energies (60-70 kJ/ mol), could be explained as easily by the diffusion-control model. These findings show how similar the observations are between proponents of the two models it is only the interpretation of the mechanism that differs. 

Delivery systems based on dissolution controlled 156 release coated technologies... 

The dissolution controlled release matrix systems provide sustained release profiles i.e., the active drugs in these systems are released continuously at a slow rate to provide a long-term therapeutic effect. Unlike diffusion controlled release coated systems, release profiles from dissolution controlled release coated systems do not follow zero-order kinetics but fall within the classification of delayed release systems,4 pulsatile or repeat-action systems,5 and sustained release systems.3... 

Although examples of delivery systems using the parenteral and oral (solid) routes are presented in this chapter, application of dissolution controlled release matrix and coated systems concepts can extended easily (and has been) used for many other delivery routes. 

Theoretical Considerations for Dissolution Controlled Release Matrix and Coated Systems... 

Although Eq. (5.2) seems to be simple, it is actually very complicated because of the preceding factors. However, it does provide some theoretical basis for rational design of dissolution controlled release systems. Therefore, surface area (related to particle size), solubility, and viscosity may be the parameters that could be regulated or modified to suit certain desired release profiles. 

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