Controlled Release Dosage Form

Oral Gastrointestinal tract Oral dosage forms controlled release... 

Dissolution rate tests for tablets, capsules, suspensions, suppositories, or other dosage forms. Controlled-release dosage forms or drug delivery systems also should be monitored by appropriate testing methodology. 

Chen, Y., McCall, T. W., Baichwal, A. R., and Meyer, M. C. (1999), The application of an artificial neural network and pharmacokinetic simulations in the design of controlled-release dosage forms,/. Controlled Release, 59, 33 11. 

No major ehallenges for immediate release dosage forms Controlled-release dosage forms may be needed to limit rapid absorption profile Formulations designed to overeome solubility or dissolution rate problems Salt formation Precipitation inhibitors Metastable forms Solid dispersion Complexation Lipid technologies Particle size reduetion... 

Y. Chen, T.W. McCall, A.R. Baichwal, and M.C. Meyer, The appKcation of an artificial neural netwirk and pharmacokinetic simulations in the design of controlled-release dosage form, /. Control. Release, 59 (1), 33-41,1999. 

A-1 Extended Release Solid Oral Dosage Forms Non-release Controlling Components... 

This time controlled release tablet with a designated lag time followed by a rapid release may provide an alternative to site-specific delivery of drugs with optimal absorption windows or colonic delivery of drugs that are sensitive to low pH or enzyme action for the treatment of localized conditions such as ulcerative colitis, Crohn s disease, and irritable bowel syndrome (IBS). Also, by controlling a predetermined lag time of drug from dosage form, the release behavior can be matched with the body s circadian rhythm pattern in chronotherapy. 

Glyceryl monostearate is a lubricant for tablet manufacturing and may be used to form sustained-release matrices for solid dosage forms.Sustained-release applications include the formulation of pellets for tablets or suppositories and the preparation of a veterinary bolus. Glyceryl monostearate has also been used as a matrix ingredient for a biodegradable, implantable, controlled-release dosage form. ... 

Figure 2.5 Stages in drug absorption from an extravascular administration site (stomach, small intestine, intramuscular injection). Only drug in solution is absorbed. If the rate of dissolution (K2) is less than the rate of absorption (K3) then the rate at which drug is released from the dosage form controls absorption. This permits modified or sustained-release formulations, but can also lead to bioequivalence problems.

In cases of all but intravenous adininistration, dosage forms must make the active moiety available for absorption, ie, for dmg release. This influences the bioavailabiUty and the dmg s pharmacokinetic profile. Ideally the dmg is made available to the blood for distribution and elimination at a rate equal to those processes. Through technological developments dmg product design can achieve release, absorption, and elimination rates resulting in durations of activity of 8—12 hours, ie, prolonged action/controlled release dmg products (21,22). Such products improve the compliance rate of dmg usage by patients. 

Compressed Tablets. This popular type of dosage form offers convenience, stabiUty, accuracy and precision, and good bioavadabihty of active ingredients. After the best formulation has been estabflshed, compressed tablets can be manufactured at high rates of speed on advanced equipment. Tablets can be made to achieve rapid dmg release or to produce delayed, repeat, or prolonged therapeutic action (Controlled release technology, pharmaceutical). ... 

Since the development of the Spansule brand (Smith Kline Beech am) of coated beads and granules in the late 1960s, various dmg product technologies have been developed and patented to achieve extended durations of therapeutic effects. Each of these does so by various mechanisms of control of dmg release from adrninistered dosage forms. Each method has its advantages and disadvantages, a discussion of which is available in the pharmaceutical hterature (see Drug delivery systems) (21). 

To avoid confusion, several researchers have incorporated therapeutic intention into the definition of controlled release (4—7). Thus, controUed-release pharmaceuticals release dmgs in vivo according to a predictable, therapeutically rational, programmed rate to achieve the optimal dmg concentration in the minimal time (4). Specification by release rate complements specification by quantity jointly considered, they fix the duration of dmg release. Therefore, the dmg s duration of action can become a design property of a controlled release dosage form rather than an inherent pharmacokinetic property of the dmg molecule. 

Most controlled release dosage forms administer dmg according to thek design, whether conceptually simple, eg, a fixed release rate for a fixed amount of time, or complex, eg, several different rates for different amounts of time. Alternatively, closed-loop systems contain a sensor to monitor dmg concentration or to administer dmg according to a biological need (11). 

For many drug delivery applications, the preferred method of delivery of the dosage form is by injection. For controlled release applications, the most frequently used approach to allow this method of administration is to prepare microspheres of the polymer containing the drug to be delivered. Several different techniques have been developed for the preparation of microspheres from polyanhydrides. 

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