Release Preparations

Administering Oral Nitroglycerin. Nitroglycerin is also available as oral tablets tiiat are swallowed. The nurse gives tiiis form of nitroglycerin to die patient whose stomach is empty, unless the primary health care provider orders otherwise. If nausea occurs after administration, die nurse notifies die primary healdi care provider. Taking die tablet or capsule widi food may be ordered to relieve nausea The sustained released preparation may not be crushed or chewed. 

Because of die risk of tolerance to oral nitrates developing, die primary care provider may prescribe die short-acting preparations 2 to 3 times daily, witii die last dose no later than 7 pm and die sustained release preparations once daily or twice daily at 8 AM and 2 PM. 

EP428 272 (FJlinwood appl. 17.10.1990 USA-prior. 17.10.1989). controlled release preparation ... 

Schweizer E, Patterson W, Rickels K, et al Double-blind, placebo-controlled study of a once-a-day, sustained-release preparation of alprazolam for the treatment of panic disorder. Am J Psychiatry 150 1210-1215, 1993 Seivewright N Benzodiazepine misuse by illicit drug misusers. Addiction 96 333—334, 2001... 

Chiang, C. N., Hollester, L. E., Kishimoto, A., and Barnett, G., Kinetics of a naltrexone sustained-release preparation,... 

Chlorine-releasing preparations, e.g. hypochlorite lOOOOppm av. Cb, at least 30min at room temperature Spillage of HIV contaminated blood and body fluid Use fresh solution Deteriorates on storage and may be adversely affected by organic matter... 

SUSTAINED-RELEASE PREPARATIONS. Robert Willette. Ph.D., and Gene Barnett, Ph.D., eds. NCDAI out of stock... 

Any extended release preparation ° CR—controlled-release ° EC—enteric coated ° LA—long-acting ° SR—sustained release 0 TR—time release ° SA—sustained action ° SL—sublingual ° XL—extended length ° XR—extended release... 

Avoid controlled-release preparations consider liquid Sinemet ... 

Phentermine is available as an immediate-release and a sustained-release product. In conjunction with a healthy lifestyle, 30 to 37.5 mg of phentermine is administered once daily, typically before breakfast or 1 to 2 hours following the morning meal. The dosage should be individualized some patients maybe managed adequately at 15 to 18.75 mg daily, whereas a dose of 18.75 mg twice daily may be used to minimize side effects, excluding insomnia. To lessen the risk of insomnia, dosing phentermine in the evening should be avoided. Timed-release preparations of phentermine are not recommended because phentermine s half-life is approximately 20 hours.39... 

Some extended-release preparations are designed with a coating that responds to the acidity of its environment. The polymeric coating of the medicine is formulated for stability during oral delivery and for eventual solubility at the intended organ. The contrasting acidic content of the stomach and the more basic environment of the intestines enable these formulations to function. For example, hydroxypropyl methylcellulose phthalate (HPMCP) (Fig. 14.1.3) is an enteric... 

In the above trial [70] rifaximin was dissolved in chloroform and applied by repeated painting. After the solvent had dried a red sludge persisted over the dental structures allowing a continuous antimicrobial effect. Better delivery systems, such as subgingival controlled release preparations [12], are, however, needed to fully exploit the rifaximin potential in periodontal disease. In this connection, a gum-like device [71] has been developed that allows a controlled and continuous release of the antibiotic within the oral cavity. Large double-blind controlled trials using this and other formulations are now needed to establish the best therapeutic regimen for this indication. 

Potentially important laboratory abnormalities occurring with niacin therapy include elevated liver function tests, hyperuricemia, and hyperglycemia. Niacin-associated hepatitis is more common with sustained-release preparations, and their use should be restricted to patients intolerant of regular-release products. Niacin is contraindicated in patients with active liver disease, and it may exacerbate preexisting gout and diabetes. 

Controlled- and sustained-release preparations dosed every 12 hours are bioequivalent to immediate-release preparations dosed every 6 hours. These dosage forms, compared with immediate-release preparations, have lower peaks and higher troughs. 

In nonacute situations, phenytoin may be initiated in adults at oral doses of 5 mg/kg/day and titrated upward. Subsequent dosage adjustments should be done cautiously because of nonlinearity in elimination. Most adult patients can be maintained on a single daily dose, but children often require more frequent administration. Only extended-release preparations should be used for single daily dosing. 

About 75 mg of carbidopa is required to effectively block L-AAD, but some patients may need more. Carbidopa/L-dopa is most widely used in a 25-mg/ 100-mg tablet, but 25-mg/250-mg and 10-mg/100-mg dosage forms are also available. Controlled-release preparations of carbidopa/L-dopa are available in 50-mg/200-mg and 25-mg/100-mg strengths. For patients with difficulty swallowing, an orally disintegrating tablet is available. If peripheral adverse effects are prominent, 25-mg carbidopa (Lodosyn) tablets are available. 

Lithium is usually initiated with low to moderate doses (600 mg/day divided into two to three doses) for prophylaxis, and higher doses (900 to 1,200 mg/day, divided into two to three doses) for acute mania. Immediate-release preparations should be given two to three times daily, whereas extended-release products can be given once or twice daily. After patients are stabilized, many patients can be switched to once-daily dosing. 

Sustained-release theophylline preparations improve patient compliance and achieve more consistent serum concentrations than rapid-release theophylline and aminophylline preparations. Caution should be used in switching from one sustained-release preparation to another because there are considerable variations in sustained-release characteristics. 

Figure 4 (a) Assembly for testing timed-release preparations. Redrawn from a letter typewritten on USP paper in 1957. Source From Ref. 23. (b) Continuous flow dissolution apparatus. Source From a 1968 publication by Pemarowski. 

A number of prodrugs in clinical use are esters of fatty acids. For example, haloperidol decanoate is of interest in slow-release preparations. This compound was hydrolyzed by such hydrolases as purified carboxylesterase but was reported to be stable in human blood or plasma and in a variety of rat tissue homogenates [107], The source of this apparent lack of reactivity was competitive binding to blood and tissue proteins. In other words, protein binding sequesters this very lipophilic prodrug and prevents enzymatic hydrolysis, thereby slowing its activation and prolonging its in vivo effects. 

Like bupropion, venlafaxine comes in immediate-release and extended-release preparations. The immediate-release form is taken twice a day starting at 37.5 to 75 mg/day and increased to 75 mg/day after 1 week. The effective dose range is 75-375mg/day. The extended release form is started once daily at 37.5mg/day and is also effective at 75-375 mg/day. The effective dose range is similar to the immediate-release form. 

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