Pulsatile release systems

Another approach to the pulsatile delivery of drugs with an osmotic pressure driven system has been suggested by Amidon et al. [66], This system provides the option of an immediate bolus dose and a second dose that can be timed to be released at some subsequent point following the administration of the dosage form. One or both of the doses can be composed of multiparticulates, for example, that would themselves be sustained release systems. 

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... 

Polymer-based systems. Pulsatile release of medicaments can be obtained from polymer-based delivery systems. Based on the mechanism of drug release from the polymer, these systems can be divided into various classes and subclasses. Broadly, they can be classified into three classes delivery by hydrolysis of polymers, delivery by osmotic pressure, and delivery by both hydrolytic degradation and osmotic effects. 

Before we can start to develop a model we also have to decide how to interpret the behavior observed in Fig. 2.1. The variations in insulin and glucose concentrations could be generated by a damped oscillatory system that was continuously excited by external perturbations (e.g. through interaction with the pulsatile release of other hormones). However, the variations could also represent a disturbed self-sustained oscillation, or they could be an example of deterministic chaos. Here, it is important to realize that, with a sampling period of 10 min over the considered periods of 20-24 h, the number of data points are insufficient for any statistical analysis to distinguish between the possible modes. We need to make a choice and, in the present case, our choice is to consider the insulin-glucose regulation to operate... 

In this book, the term dmg delivery system (DDS) is used as a general term to denote any type of advanced delivery system. Conventional dmg delivery systems are simple oral, topical or injection formulations. A DDS, as used here, represents a more sophisticated system which may incorporate one, or a combination, of advanced technologies such as rate-control, pulsatile release or bioresponsive release to achieve spatial and/or temporal delivery. A dmg delivery and targeting system (DDTS) specifically describes an advanced delivery system that incorporates some type of specific targeting technology (such as, for example, monoclonal antibodies) such systems are currently most advanced for use in the parenteral administration of dmgs. Also, rate-control and dmg targeting are treated as two separate issues in this book and are dealt with in detail in Chapters 4 and 5 respectively. 

Most pulsatile delivery systems are reservoir devices coated with a barrier layer. The barrier dissolves or erodes after a specified lag time, after which the drug is released rapidly from the reservoir core. In general, the lag time prior to drug release can be controlled by the thickness of the coating layer. 

Several delivery systems with sigmoidal or pulsatile release patterns were derived on this ion exchange. The sigmoidal release system (SRS) consisted of pellet cores, containing drug and succinic acid, coated with Eudragit The lag time was controlled by the... 

The release profile of systems based on permeability changes appeared to depend strongly on the physicochemical properties of the drug and its interaction with the membrane. A pulsatile release profile may be obtained for some particular drug molecules in a specific formulation but cannot be generally applied to all drugs. 

Various pulsatile release methods for oral drug delivery include the Port system (a semipermeable capsule containing an osmotic charge and an insolnble ping) and Chronset system (an osmoticaUy active compartment in a semipermeable cap). 

The preceding studies, as well as other studies on controlled release from numerous other laboratories are but examples of how polymers may be useful in controlling drug release. These delivery concepts may not only be of value in their own right, but will hopefully stimulate additional research in the release of polypeptides, the creation of new bioerodible polymers, and the design of pulsatile delivery systems. 

Fig. 4.2-12 Use of the reverse dimerization system to control protein secretion in mammalian cells, (a) Scheme for inducible secretion, (b) Chemical structure of monomeric ligand AP21998. (c) Pulsatile release of insulin from engineered cells. 

R. Ishino, H. Yoshino, Y. Hirakawa and K. Noda, Design and preparation of pulsatile release tablet as a new oral drug delivery system, Chem. Pharm. Bull., 40, 3036-3041 (1992). 

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