Pulsatility

Another example was done by Opitz et al. They utilized P4HB scaffolds to produce viable ovine blood vessels, and then implanted the blood vessels in the systemic circulation of sheep. Enzymatically derived vascular smooth muscle cells (vSMC) were seeded on the scaffolds both under pulsatile flow and static conditions. Mechanical properties of bioreactor-cultured blood vessels which were obtained from tissue engineering approached those of native aorta. 

Hoerstrup SP, Sodian R, Sperling JS, Vacanti JP, and Mayer JE Jr. New pulsatile bioreactor for in vitro formation of tissue engineered heart valves[J]. Tissue Eng, 2000, 6(1), 75-79. 

It is well established that the concentration of oxytocin in plasma is increased in a pulsatile manner prior to, and during, parturition in a wide... 

Shinohara K., Morofushi M., Funabashi T., Mitsushima D., et al. (2000). Effects of 5alpha-androst-16-en-3alpha-ol on the pulsatile secretion of luteinizing hormone in human females. Chem Senses 25, 465-467. 

Pain associated with cluster headache differs from migraine and TTH in that it is severe, intermittent, and short in duration.6 Headaches typically occur at night, but attacks may occur multiple times per day.9 The pain is usually unilateral, but unlike migraine it is not described as pulsatile.6 Aura is not a feature,... 

New routes of administration transmucosal specific regional uptake in gastrointestinal tract New pattern of drug release bolus/flrst order/pulsatile feedback control disease-related release of drug... 

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. 

Even the most superficial evaluation of bioequivalency requirements for controlled-release products will indicate that for some of these products, at least, the conventional AUC, Tmax, and Cmax measures of bioequivalency may well be insufficient. Thus, for a non-pulsatile sustained-release product with a dosing interval of 24 hours (as compared to 4 hours for the noncontrolled product), the time period during which plasma concentrations are maintained at essentially a plateau level might well be regarded as of critical... 

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. 

As noted in the patent for this system, pulsatile systems are expected to have numerous applications in drug delivery, including site-specific delivery in the GI tract and bid (twice-a-day) dosing of two pulsatile systems that simulates qid (four times a day) dosing of immediately available products. The latter concept is expected to have a particular advantage for those drugs that have high first-pass metabolism. 

Figure 21 Effect of film thickness on the in vitro release time for pulsatile capsules. (From Ref. 66.)...

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.)...

Figure 19 Edrophonium chloride release from poly(2-acrylamido-2-methylpropane sulfonic acid-co-butyl methacrylate) gel in distilled deionized water with various pulsatile electric currents. (From Ref. 45.)...

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

Feinberg, I. March, J. D. (1988). Cyclic delta peaks during sleep result of a pulsatile endocrine process [letter]. Arch. Gen. Psychiat. 45, 1141-2. 

In addition, the effects of pulsatile flow cannot be ignored. One measure of the impact of oscillary flow is the Wcmersley parameter (a) a= h/2tt f/v where r is the tube radius, f the frequency of oscillation and v is the kinematic viscosity of the fluid (Wcmersley, 1955). The degree of departure from parabolic flow increases with and frequency effects may become important in straight tubes when a > 1 (Ultman, 1985). For conditions of these experiments, a exceeds one to beyond the third generation. 

Peppas, N. A., Fundamentals of pH- and temperature-sensitive delivery systems, in Pulsatile Drug Delivery, Wissenschaftliche Verlagesellschaft (R. Gurny, H.E. Junginger, and N. A. Peppas, Eds.), pp. 41-56. Stuttgart (1993). 

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