Modified-release systems, types

Different types of modified release systems can be defined [4, 8] ... 

Bracketing design is applicable to most types of drug products, including immediate- and modified-release oral solids, liquids, semisolids, and injectables. Certain types of drug products, such as MDIs, DPIs, and transdermal delivery systems, may not be amenable to, or may need additional justification for, bracketing design. 

Release modeling system. Contains database of chemicals and characteristics which may be modified by user. User selects chemical, weather conditions and type of release for simple or heavy gas modeling. Output is numeric for times and distances with graphic capabilities. 

FIGURE 18.5 Schematic representation of types of multienzyme systems carrying out a metabolic pathway (a) Physically separate, soluble enzymes with diffusing intermediates, (b) A multienzyme complex. Substrate enters the complex, becomes covalently bound and then sequentially modified by enzymes Ei to E5 before product is released. No intermediates are free to diffuse away, (c) A membrane-bound multienzyme system. 

The partitioning of the activated inhibitor between direct covalent inactivation of the enzyme and release into solution is an important issue for mechanism-based inactivators. The partition ratio is of value as a quantitative measure of inactivation efficiency, as described above. This value is also important in assessing the suitability of a compound as a drug for clinical use. If the partition ratio is high, this means that a significant proportion of the activated inhibitor molecules is not sequestered as a covalent adduct with the target enzyme but instead is released into solution. Once released, the compound can diffuse away to covalently modify other proteins within the cell, tissue, or systemic circulation. This could then lead to the same types of potential clinical liabilities that were discussed earlier in this chapter in the context of affinity labels, and would therefore erode the potential therapeutic index for such a compound. 

The autonomic nervous system (ANS) modifies contractile activity of both types of smooth muscle. As discussed in Chapter 9, the ANS innervates the smooth muscle layer in a very diffuse manner, so neurotransmitter is released over a wide area of muscle. Typically, the effects of sympathetic and parasympathetic stimulation in a given tissue oppose each other one system enhances contractile activity while the other inhibits it. The specific effects (excitatory or inhibitory) that the two divisions of the ANS have on a given smooth muscle depend upon its location. 

A buccal drug delivery system is applied to a specific area on the buccal membrane. Moreover, the delivery system ean be designed to be unidirectional in drug release so that it can be protected from the loeal environment of the oral cavity. It also permits the inclusion of a permeation enhancer/protease inhibitor or pH modifier in the formulation to modulate the membrane or the tablet-mucosal environment at that particular application site. While the irritation is limited to the well-defined area, the systemic toxicity of these enhancers/inhibitors and modifiers can be reduced. The buccal mucosa is well suited for this type of modification as it is less prone to irreversible damage [9]. In the event of drug toxicity, delivery can be terminated promptly by removal of the dosage form. 

A new generation of transdermal drug delivery (TDD) system was developed to contain one or more skin permeation enhancers in the surface adhesive coating layers. This TDD system has been found, experimentally, to release the enhancers to the surface of stratum corneum to modify the skin s barrier properties, prior to the controlled delivery of the active drug. The extent of enhancement in skin permeability appears to be dependent upon the chemical structure of drug to be delivered transdermally as well as the type and the concentration of enhancer used. The mechanism of skin permeation enhancement have been explored and are analyzed in this report. 

This new type of transdermal drug delivery system is capable of releasing one or a combination of two or more skin permeation enhancers to the stratum corneum surface in order to modify the skin s barrier properties (10), prior to the controlled delivery... 

---