Controlled-release products drugs

Traditionally, the ideal extended-release product has been conceived as providing essentially stable blood levels over the whole dosing frequency interval. Thus, unlike the saw-edge blood concentration time profile of a non-controlled-release product that may show rather wild fluctuations between sub- and su-pratherapeutic blood levels, the ideal extended-release product avoids both nontherapeutic blood levels and those likely to have an increased frequency of dose-related side effects. However, in recent years con-trolled-release products that deliberately exploit a pulsatile drug release time profile have also attracted attention. 

Rapid-release products are another class of con-trolled-release drug-delivery systems of growing interest to pharmaceutical scientists. For this type of product rapidity of response is the key parameter. If a conventional non-controlled-release product gives the therapeutic response in one hour, a rapid-release product might be designed so as to yield such a response in 20 minutes. 

Another aspect related to control release of drugs concerns the type of structures that currently appear to be working. Not unexpectedly, because of compatibility and degradation purposes, most of the effort on the control release formulations includes polymers that have both a hydrophobic and hydrophilic portion with the material necessarily containing atoms in addition to carbon. Another concern is that the products of degradation are not toxic or do not form toxic materials. It has also been found that amorphous materials appear to be better since they are more flexible and permit more ready entrance of potential degrad-ative compounds. 

For example, a 505(b)(2) application would be appropriate for a controlled release product that is bioinequivalent to a reference listed drug where... 

Rathbone, M. J, Macmillan, K. L., JoChle, W., Boland, M., and Inskeep, E. K. (1998), Controlled release products for the control of the estrous cycle in cattle, sheep, goats, deer, pigs, and horses, Crit. Rev. Ther. Drug Carrier Syst., 15, 285-380. 

Malinowski, H. I, and Marroum, P. J. (1999), Encyclopedia of Controlled Drug Delivery, vols. 1 and 2, Food and Drug Administration Requirements for Controlled Release Products, John Wiley Sons, New York, vol. 1, pp. 381-395. 

The slowest step in a kinetic process is the rate-limiting step. Except for controlled release products, disintegration of a solid oral drug product is usually... 

An immediate release product would require some special feature to warrant the increased cost of production when compared to a conventional capsule or tablet. Therefore, the major commercial use of pellets prepared by extrusion/spheronization is in the preparation of controlled release products and there are several highly successful products available. In particular the ability to produce pellets with a high drug loading offers advantages over alternative methods of forming pellets. 

Intraruminal drug delivery systems are products administered to, and retained in, the rumen of ruminant animals (e.g., cattle, sheep) and formulated to deliver drugs over extended periods (months). Many controlled-release intraruminal drug delivery systems have been developed over the last few decades, and for extensive reviews on intraruminal drug delivery the reader is referred to Refs. 11, 13, and 14. 

Insoluble salts may be prepared using high molecular weight counterions to reduce the solubility of the drug for formulation of a suspension, to improve chemical stability, provide improvements in solid-state stability, reduce acid lability and permit formulation of tasteless or controlled release products. Erythromycin stearate, which is poorly soluble in acidic media (an enteric salt), is less prone to decomposition in gastric fluids than the more acid-soluble free base. 

Other aspects of product performance should be considered in a specification. For example, in an immediate-release tablet, the drug should dissolve in a few minutes, not 45 minutes or longer. A controlled-release product should deliver the drug within the profile defined during development. Thus, tests that demonstrate that the state of the API within the dosage unit is in the specified physical form may increase the reliability of product performance. 

Controlled-release products typically employ one or more polymeric excipients to control drug release. Such polymers include artificial or natural... 

---