Slow-release formulation

Vinyl Phosphates. Dichlorvos [62-73-7] 0,0-dimethyl 0-(2,2-dichloroviayl) phosphate, (CH20)2P(0)0CH=CCl2 (bp 140°C at 27 kPa, d 1.314, vp 1.6 Pa at 20°C), is soluble ia water to about 10 g/L. The half-hfe ia water is 8 h. The rat oral LD qS are 80, 56 mg/kg. Dichlorvos is used ia aerosols and sugar baits to control flies and mosquitoes. Slow release formulations have been used ia plastic strips and pet collars to control animal ectoparasites. 

Slow release formulations incorporate nonpersistent compounds, eg, methyl parathion, insect growth regulators, and sex pheromones, in a variety of granular, laminated, microencapsulated, and hoUow-ftber preparations. 

All products have carbamazepine as active ingredients. Retard is slow release formulations. The products have different pharmacokinetics and are not bioequivalent. 

Both products have metoprolol as active ingredient. ZOC is a slow release formulation. 

Diclofenac (a non-steroidal anti-inflammatory drug) is marketed as Voltarol oral slow-release formulations. 

Increasing numbers of drugs are being formulated in a way that permits delivery through the skin. We tend to think of the skin as a poorly permeable layer but in fact it can transport drugs quite rapidly and is a convenient way of giving drugs which we want to leach out of a slow release formulation over a period of a few to many hours. 

Short half-life necessitating two or three daily doses slow-release formulations available. 

Slow release formulations are available for tried and tested substances, e.g. ketoprofen and naproxen, if increased duration of effect is needed. 

Nausea and diarrhea are common early side effects. Gastrointestinal symptoms may improve with dose reduction or with ingestion of lithium at meals. Slow-release formulations are more often associated with nausea, whereas sustained-release preparations are more commonly associated with diarrhea. 

Nifedipine has a rapid onset of action and a short elimination half-life. A slow-release formulation allows a single daily dose to be prescribed and prevents reflex tachycardia. Newer, second- and third-generation dihydropyridines, have a slower onset and a longer elimination half-life. This makes special pharmaceutical formulations unnecessary. 

Verapamil does not induce reflex tachycardia. However, its short elimination half-life requires thrice-daily dosing. A slow-release formulation... 

Procainamide is eliminated by hepatic metabolism to NAPA and by renal elimination. Its half-life is only 3-4 hours, which necessitates frequent dosing or use of a slow-release formulation (the usual practice). NAPA is eliminated by the kidneys. Thus, procainamide dosage must be reduced in patients with renal failure. The reduced volume of distribution and renal clearance associated with heart failure also require reduction in dosage. The half-life of NAPA is considerably longer than that of procainamide, and it therefore accumulates more slowly. Thus, it is important to measure plasma levels of both procainamide and NAPA, especially in patients with circulatory or renal impairment. 

Naproxen is a naphthylpropionic acid derivative. It is the only NSAID presently marketed as a single enantiomer. Naproxen s free fraction is significantly higher in women than in men, but half-life is similar in both sexes (Table 36-1). Naproxen is effective for the usual rheumatologic indications and is available in a slow-release formulation, as an oral suspension, and over the counter. A topical preparation and an ophthalmic solution are also available. 

A number of reports in the 1970s and 1980s demonstrated that periplanone-B was highly active to male B. orientalis in both behavioral and EAG assays. Periplanone-B in slow-release formulations also attracted Blatta males to traps in infested swine farms (C. Schal, unpublished data). However, it remains unclear... 

One approach is to optimize the levels of electron acceptors. Slow release formulations of inorganic peroxides, such as magnesium peroxide, have recently been used with success. Nitrate may be added, although there are sometimes regulatory limitations on the amount of this material that may be added to groundwater. Ferric iron availability may be manipulated by adding ligands. 

Caffeine is used medicinally as a CNS stimulant, usually combined with another therapeutic agent, as in compound analgesic preparations. Theobromine is of value as a diuretic and smooth muscle relaxant, but is not now routinely used. Theophylline is an important smooth muscle relaxant for relief of bronchospasm, and is frequently dispensed in slow-release formulations to reduce side-effects. It is also available as aminophylline (a more soluble preparation containing theophylline with ethylenediamine) and choline theophyllinate (theophylline and choline). The alkaloids may be isolated from natural sources, or obtained by total or partial synthesis. 

Patat A, Rosenzweig P, Enslen M, Trocherie S, Miget N, Bozon M, Allain H, Gandon J. Effects of a new slow release formulation of caffeine on EEG, psychomotor, and cognitive functions in sleep-deprived subjects. Hum Psychopharmacol 2000 15 153-170. 

Quinidine is 70-80% bioavailable following oral administration. It is 80% bound to albumin and a i-acid glycoprotein. It is eliminated primarily by hepatic metabolism. The principal metabolite, 3-hydroxy quinidine is biologically active with half the activity of the parent compound. Twenty percent of the quinidine dose appears in the unchanged form in the urine. The elimination half-life is 6-8 hours. Quinidine is usually administered in a slow release formulation, eg, that of the gluconate salt. 

Octreotide acetate injectable suspension (octreotide long-acting release Sandostatin LAR) is a slow-release formulation in which octreotide is incorporated into microspheres. It is instituted only after a brief course of shorter-acting octreotide has been demonstrated to be effective and tolerated. The microspheres must be carefully put into suspension and immediately injected into a gluteal muscle. Injections into alternate gluteal muscles are repeated at 4-week intervals in doses of 20-40 mg. Octreotide is extremely costly. 

Furthermore, there is a direct correlation between the paclitaxel dose delivered to the artery and the vascular response when examined in the porcine coronary artery model. The slow-release formulation demonstrated patent lumen, struts covered by stable intima and re-endothelializa-tion with minimal fibrin, whereas the fast-release formulation resulted in noticeable fibrin accumulation, an indication of higher level of drug exposure to the arteries (Fig. 10). It should be noted that the 8.8% slow-release formulation is currently marketed as TAXUS SR and has demonstrated efficacy in clinical studies this is discussed in the next section. 

WO 9 531 976 (Novo Nordisk appl. 17.5.1995 DK-prior. 20.5.1994). slow release formulation ... 

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