Bolus release

The discharge of entrapped contents can be controlled to produce bolus release with a single high amplitude ultrasonic pulse, or sustained release through a series of low amplitude pulses. These options could be particularly valuable in those cases where it is important to raise the local concentration to a therapeutic level and maintain it for some time. 

Bolus release Administration of a dmg over a relatively quick amount of time (less than 5 min) in comparison to a sustained delivery which can last over hours Bonding bridge Bridge between two sand grains made up by a polymer or an aerogel Bronsted acidity Chemical compound presenting Bronsted acid sites that are able to lose a proton... 

In sustained-release implants, the general approach is to provide a barrier between the body fluid and insulin. This barrier can be microporous, where the rate of insulin release is diffusion-controlled, or it can be an erodible material that dissolves gradually and releases the entrapped insulin. By using mechanical stress or transmitted energy, externally modulated bolus release of insulin can be obtained. Even more sophisticated selfregulating (closed-loop) systems are also under development. 

The principal arninoglycoside toxicides are neuromuscular paralysis, ototoxicity, and nephrotoxicity. Neuromuscular paralysis is a relatively rare complication resulting from high aminoglycoside concentrations at the neuromuscular junctions following, for example, rapid bolus intravenous injection or peritoneal instillation, rather than the normal intravenous infusion. The mechanism apparentiy involves an inhibition of both the presynaptic release of acetylcholine and the acetylcholine postsynaptic receptors (51). 

Polyethers such as monensin, lasalocid, salinomycin, and narasin are sold in many countries in crystalline or highly purified forms for incorporation into feeds or sustained-release bolus devices (see Controlled-RELEASE technology). There are also mycelial or biomass products, especially in the United States. The mycelial products are generally prepared by separation of the mycelium and then drying by azeotropic evaporation, fluid-bed driers, continuous tray driers, flash driers, and other types of commercial driers (163). In countries allowing biomass products, crystalline polyethers may be added to increase the potency of the product. 

Ivermectin is widely used as an endectocide for catde as an injectable, oral, topical, or slow release bolus for sheep as an injectable or oral formulation for swine as an injectable for horses as a paste or drench and for goats as an injectable or oral formulation. Ivermectin has recently been introduced for heartworm prophylaxis in dogs and it is being studied for use with cats, many other mammals, birds, fish, and reptiles. 

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

The release of steroids such as progesterone from films of PCL and its copolymers with lactic acid has been shown to be rapid (Fig. 10) and to exhibit the expected (time)l/2 kinetics when corrected for the contribution of an aqueous boundary layer (68). The kinetics were consistent with phase separation of the steroid in the polymer and a Fickian diffusion process. The release rates, reflecting the permeability coefficient, depended on the method of film preparation and were greater with compression molded films than solution cast films. In vivo release rates from films implanted in rabbits was very rapid, being essentially identical to the rate of excretion of a bolus injection of progesterone, i. e., the rate of excretion rather than the rate of release from the polymer was rate determining. 

A current area of interest is the use of AB cements as devices for the controlled release of biologically active species (Allen et al, 1984). AB cements can be formulated to be degradable and to release bioactive elements when placed in appropriate environments. These elements can be incorporated into the cement matrix as either the cation or the anion cement former. Special copper/cobalt phosphates/selenates have been prepared which, when placed as boluses in the rumens of cattle and sheep, have the ability to decompose and release the essential trace elements copper, cobalt and selenium in a sustained fashion over many months (Chapter 6). Although practical examples are confined to phosphate cements, others are known which are based on a variety of anions polyacrylate (Chapter 5), oxychlorides and oxysulphates (Chapter 7) and a variety of organic chelating anions (Chapter 9). The number of cements available for this purpose is very great. 

Currently, the most advanced form of insulin therapy is the insulin pump, also referred to as continuous subcutaneous insulin infusion (CSII). Using the short- or rapid-acting insulins only, these pumps are programmed to provide a slow release of small amounts of insulin as the basal portion of therapy, and then larger bolus doses are injected by the patient to account for the consumption of food. 

In vivo Release of Desmopressin and Somatostatin. The in vivo release of Desmopressin and Somatostatin after subcutaneous and intramuscular injections of the peptide in the cubic or the lamellar phase has been studied in the rabbit. Blood was sampled at regular intervals, and systemically absorbed Desmopressin and Somatostatin were determined as the specific immunoreactitvity in plasma of the actual peptide. For details of the analyses with dDAVP, consult ref. 9. For comparison, Desmopressin-like and Somatostatin-like immunoreactitvity (dDAVP-LI and SRIF-LI) in plasma after intravenous bolus injections of the two peptides were determined as well. 

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... 

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. 

JR Egerton, D Suhayda, CH Eary. Prophylaxis of nematode infections in cattle with an indwelling, ruminoreticular ivermectin sustained release bolus. Vet Parasitol 74 614-617, 1986. 

JL Zingerman, JR Cardinal, RT Chern, J Holste, JB Williams, B Eckenhoff, JT Wright. The in vitro and in vivo performance of an osmotically controlled delivery system-IVOMEC SR Bolus . J Controlled Release 47 1-11, 1997. 

Yeates, G., Dimander, S.-O., Waller Peter, J. and Hoglund, J. (2003). Soil nematode populations beneath faecal pats from grazing cattle treated with the ivermectin sustained-release bolus or fed the nematophagous fungus Duddingtonia flagrans to control nematode parasites . Acta Agricultural Scandinavica, Section A, Animal Science, 53, 197-206. 

Domestic sheep (Ovis aries) fed a low-zinc diet (2.2 mg Zn/kg DW diet) for 50 days, when compared to those fed a zinc-adequate diet (33 mg Zn/kg DW diet), excreted less zinc (<4 mg daily vs. 23 to 25), consumed less food (409 g daily vs. 898), and had lower plasma zinc concentrations (0.18 mg/L vs. 0.53 to 0.58) a reduction in plasma alkaline phosphatase activity and an increase in plasma zinc binding capacity were also noted (Khandaker and Telfer 1990). Sensitive indicators of zinc deficiency in lambs include significant reductions in plasma alkaline phosphatase activity and plasma zinc concentrations signs were clearly evident in lambs fed 10.8 mg Zn/kg DW diet for 50 to 180 days (Vergnes et al. 1990). A normal diet for lambs contains 124 to 130 mg Zn/kg DW ration vs. 33 for adults (Vergnes et al. 1990). One recommended treatment for zinc-deficient sheep is ruminal insertion of zinc-containing boluses every 40 days bolus zinc release is about 107 mg daily (Khandaker and Telfer 1990). 

Bolus sustained release of 7 mg famphur/kg BW daily Intravenous injection Completely effective against Gulf Coast tick, partial control of lone star tick, ineffective against American dog tick 2... 

Hair, J.A., W.J. Gladney, R.B. Davey, R.O. Drummond, and P.D. Teel. 1979. Sustained-release famphur bolus for control of Boophilus ticks. Jour. Econ. Entomol. 72 135-138. 

Teel, P.D., J.A. Hair, and L.G. Stratton. 1979. Laboratory evaluation of a sustained-release famphur bolus against Gulf Coast and lone star ticks feeding on Hereford heifers. Jour. Econ. Entomol. 72 230-233. 

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