Pulsatile release

Figure 16 Pulsatile release rate of indomethacin in response to a stepwise temperature change between 20°C and 30°C in phosphate-buffered saline (pH 7.4). (From Ref. 36.)...

Prast, H., Died, H. Philippu, A. (1992). Pulsatile release of histamine in the hypothalamus of conscious rats. J. Auton. Nerv. Syst. 39, 105-10. 

Jiang and Zhu (2000) and Qiu and Zhu (2001) have reported the fabrication of multilayered devices composed of stacks of compression-molded disks of alternating compositions. One type of disk is either P(SA-EG) or P[SA-co-TMAgly)-Z>-EG] and the other is a pH-sensitive, protein-loaded blend of, for example, poly(methacrylic acid) and polyethoxazoline. The release of model proteins, myoglobin, bovine serum albumin, and FITC-dextran, and compounds such as brilliant blue have been studied and pulsatile release profiles have been demonstrated (Jiang and Zhu, 2000 Qiu and Zhu, 2001). 

The three best-known examples of biochemical oscillations were found during the decade 1965-1975 [40,41]. These include the peroxidase reaction, glycolytic oscillations in yeast and muscle, and the pulsatile release of cAMP signals in Dictyostelium amoebae (see Section V). Another decade passed before the development of Ca " " fluorescent probes led to the discovery of oscillations in intracellular Ca +. Oscillations in cytosolic Ca " " have since been found in a variety of cells where they can arise spontaneously, or after stimulation by hormones or neurotransmitters. Their period can range from seconds to minutes, depending on the cell type [56]. The oscillations are often accompanied by propagation of intracellular or intercellular Ca " " waves. The importance of Ca + oscillations and waves stems from the major role played by this ion in the control of many key cellular processes—for example, gene expression or neurotransmitter secretion. 

Therapeutic control of AH cells. GnRH is used in hypothalamic infertility in women to stimulate FSH and LH secretion and to induce ovulation. For this purpose, it is necessary to mimic the physiologic intermittent "pulsatile" release (approx, every 90 min) by means of a programmed infusion pump. 

GnRH analogues (see Chapter 59) can induce chemical castration by suppressing the pulsatile release of LH and FSH, hence inhibiting testicular steroidogenesis. Administration of these compounds reduces circulating testosterone levels. These compounds are inhaled, injected subcutaneously, or implanted subcutaneously. They are used in males in the treatment of precocious puberty and carcinoma of the prostate. 

Fig. 19.7 Oscillating change of temperature (a) and time-dependent pulsatile release of BSA (b) PNIPAM hydrogel in phosphate buffer, pH = 7.4 (1) and water (2) at 25°C and 40°C...

Fig. 1. Pulsatile release rate of indomethacin from poly(IPAAm-co-BMA) gel (BMA 5 wt %) in response to stepwise temperature changes between 10°C and 30°C...

Luteinizing hormone-releasing hormone (LHRH) is used in the treatment of infertility (1). It induces pulsatile release of gonadotropin, and excessive stimulation can... 

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. 

A pulsatile release diltiazem hydrochloride dosage form with a blend of fast, medium, and slow release fractions of a multilayered diltiazem bead was designed.32 Polymeric membrane coating was applied to modulate the time of release. The fast, medium, and slow release fractions... 

Iskakov, R. M., Kikuchi, A., and Okano, T. Time-programmed pulsatile release of dextran from calcium-alginate gel beads coated with carboxy-re-propylacrylamide copolymers. J. Contr. Rel. 80 57-68, 2002. 

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... 

As a final comment to this section, let us note that experiments have also been performed to examine the possible physiological function of the oscillatory insulin secretion. An obvious question of interest was whether pulsatile release of insulin... 

In general, secretion of hormones does not occur at a constant rate. In some cases, secretion is pulsatile, occurring in short bursts, as for many pituitary hormones. The biochemical basis of this pulsatile release is not fully understood, but the release pattern may have profound effects on hormone function, i.e., the pulsatile administration of luteinizing hormone releasing hormone (LHRH) stimulates the release of LH by the pituitary, whereas the constant infusion of the same amount of hormone per unit time has the opposite effect. 

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. 

Pulsatile release when the device actively controls the dosage released following predefined parameters... 

An effervescent mixture of citric acid and sodium bicarbonate was incorporated in a tablet core coated with ethyl cellulose. The carbon dioxide development after water penetration into the core resulted in a pulsatile release after rupture of the coating, which was strongly dependent on the mechanical properties of the coating layer The weak and nonllexible ethyl cellulose film ruptured sufficiently when... 

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