Controlled-release preparations

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

Avoid controlled-release preparations consider liquid Sinemet ... 

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. 

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. 

The prescribing physician should be notified immediately if tics or psychosis (usually paranoia) develop. The medication should always be stopped when psychosis occurs. We once said the same about tics, but recent research suggests that stimulants may not worsen tics. Methylphenidate is now available in a controlled-release preparation (Concerta), which can be prescribed once daily. One key advantage to once-daily dosing is not pharmacological, but rather that it avoids the stigma children may experience when they need to go to the school nurse s office to receive their afternoon dose. Focalin is the active isomer of methylphenidate. 

Sugar-coated products have been marketed that contain KCl in a wax matrix (Slow-K and Kaon-Ct) and are purportedly slow- and controlled-release preparations. Available evidence indicates that these slow-release forms of KCl are occasionally capable of causing local tissue damage and therefore prol5ably should be used with caution for K+ supplementation. Solutions of potassium gluconate, like the tablets, also have been associated with intestinal ulceration. Microencapsulated KCl preparations Micro-K, K-Dur) that are neither enteric coated nor contained within a wax matrix appear to be superior to the wax matrix formulation. 

Tyrer, S.P., Peat, M.A., Minty, P.S., Luchini, A., Glud, V., and Am-disen, A. (1982) Bioavailability of lithium carbonate and lithium citrate a comparison of two controlled-release preparations. Pharmatherapeutica 3 243-246. 

Modified Lignins as the Carriers for Controlled Release Preparations... 

Dosages and routes of administration Oxycodone is given by mouth in single doses of 5-10 mg or as controlled release preparations with doses of 40 mg (Cairns, 2001). Rectal administration is also possible. Oral formulations often contain combinations with paracetamol or acetylsalicylic acid. 

Depending on the country where the drug is manufactured, a number of different time-release preparations are available. Palladone , a controlled-release preparation consisting of hydromorphone HC1 pellets, was withdrawn from the U.S. market in 2005. When taken with alcohol the pellets rapidly released their contents leading to dangerously elevated peak plasma concentrations.60 Interaction with ethanol and dose dumping is not the only concern. Any CNS depressant may enhance the depressant effects of hydromorphone. 

Levodopa-carbidopa is also available in a con-trolled-release preparation (Sinemet CR) that is absorbed more slowly and is intended to provide prolonged effects.48 The use of this controlled-release preparation may be helpful in patients who respond well to levodopa initially but experience dyskinesias... 

Management of the motor fluctuations has largely been concentrated on attempts to prolong the duration of action of the drug, either by the use of controlled release preparations to obtain "smooth" concentration-time curves or by combining dopa with deprenyl or bromocriptine. Long-term (about 16 years) follow-up studies of patients have shown that the mean "functional" status of the patient approaches pretreatment levels after 5 years, and by 16 years all surviving patients were functionally less well than at the initiation of therapy. From such studies it may be concluded that... 

Glipaide (Controlled Release) 24 Controlled-release preparation produces sustained plasma levels... 

Narisawa, S., Nagata, M., Ito, T., Yoshino, H., Hirakawa, Y., and Noda, K. (1995), Drug release behavior in gastrointestinal tract of beagle dogs from multiple unit type rate-controlled or time-controlled release preparations coated with insoluble polymer-based film, I. Controlled Release, 33,253-260. 

Various strategies have been devised to overcome these problems. Controlled release preparations of levodopa tend to be associated with an inadequate initial response and disabling dyskinesia at the end of the dose. A more effective approach appears to be the use of a COMT inhibitor, e.g. entacapone, which can sometimes aUay early end-of-dose deterioration without causing dyskinesia. This is now the main indication for its use. In any event, many patients with Parkinson s disease take at least two and sometimes more drugs at frequent intervals each day, an outcome that tends to rule their lives. 

Table 3 Controlled-release preparations for oral delivery...

Narisawa, S. Nagata, M. Danyoshi, C. Yoshino, H. Murata, K. Hirakawa, Y. Noda, K. An organic acid-induced sigmoidal release system for oral controlled-release preparations. Pharm. Res. 1994, 11 (1), 111-116. 

In vivo bioavailability data for sustained/controlled release preparations. 

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