Modified release preparations

Slow-K is a modified-release preparation containing potassium chloride. Patients taking Slow-K are advised to take the tablets in an upright position, while standing or sitting. The tablets should be swallowed whole with plenty of water, to avoid gastrointestinal irritation. 

Lescol XL, is a modified-release preparation of fluvastatin 80 mg, a statin. 

The antiplatelet/antithrombotic activity of dipyridamole has been demonstrated in laboratory and in animal models, and has been shown to inhibit platelet aggregation and vessel-wall thrombogenesis [9-11]. Dipyridamole has been given either alone or with aspirin in the management of myocardial infarction and stroke. For the secondary prevention of stroke or transient ischemic attack, the drug may be given as a modified-release preparation in a dose of 200 mg twice daily. Dipyridamole administered intravenously results in a marked coronary vasodilation and is used in stress testing in patients with ischemic heart disease [5]. 

Many patients prefer to have a different type of iron preparation to ferrous sulphate tablets - they find they cause them fewer side-effects. The reason for this is generally that the product they prefer either contains less iron to start with or is a modified-release preparation. 

Modified-release preparations release iron gradually so less iron is present in the gastrointestinal tract at any one time. However, because they are modified-release, these preparations are likely to carry the iron past the first part of the duodenum into an area of the gut where iron absorption may be poor. The low incidence of side-effects may reflect the small amounts of iron available for absorption under these conditions and so the preparations have no therapeutic advantage and should not be used. 

SUCRALFATE BRONCHODILATORS -THEOPHYLLINE Possibly 1 theophylline levels (with modified-release preparations) Possibly 1 absorption Watch for poor response to theophylline and monitor levels... 

Pharmacists and pharmacy technicians should ensure that they are supplying the correct drug and the correct presentation of the drug (e.g. not supplying a modified-release preparation when a standard (non-modified-release) was requested). 

These are flexible, usually one piece and often contain liquids, for example, fish liver oil capsules. The soft gelatin capsules can be coated to produce modified-release preparations, or enteric resistant coatings can be added to allow for absorption from the intestine. 

Consider the formulation Osmosin was a modified release preparation of indomethacin. It was designed to release the active drug under osmotic control. Instead it allowed its potassium content to be released in a way that caused perforation of the small bowel distal to the duodenum. The drug provides an example of the formulation causing the problem, and the drug serves as a reminder that consideration needs to be given to the formulation as a possible cause of trouble which can be remedied by reformulation. 

After five years of treatment about half of patients will experience the drug becoming less effective and a gradual recurrence of symptoms, especially hypokinesia, occurs. Another type of deterioration is the shortening of action of each dose with time ( end of dose deterioration ) and unpredictable fluctuations ( on-off effect ) in response to treatment, which can happen quite abmptly. It is not known why these effects occur, but they may be due to advance of the disease process. End of dose deterioration can be alleviated to a certain extent by the use of modified release preparations of levodopa or by the concurrent use of catechol-o-methyl transferase (COMT) inhibitors, for example enta-capone. COMT inhibitors prevent the peripheral breakdown of levodopa by an enzyme, COMT. 

I. Ghebre-Sellassie, U. Iyer, D. Hubert, and M. B. Fawzi, Characterization of a new water-based coating for modified-release preparations, Pharm. Tech. 96-106(1988). 

The overall picture is that concurrent use need not be avoided with standard preparations, although some individuals may be affected so the outcome should be monitored. With modified-release preparations it would seem advisable to avoid concurrent administration (1 to 2 hours is usually enough in other similar cases of interactions with antacids). Again, the outcome should be monitored. 

Nifedipine. In a small study in 18 patients, low-dose aspirin 100 mg daily for 2 weeks did not alter the blood pressure lowering effect of nifedipine 30 to 60 mg daily, given as a modified-release preparation. 

Some modified-release preparations of felodipine, nifedipine, and nisoldipine show markedly increased levels when given with food, particularly when high in fat. The bioavailability of lercanidipine is markedly increased by food, and it should therefore be given on an empty stomach. Manidipine should be given with food, as this improves its absorption. Food modestly decreases the rate and extent of absorption of nimodipine capsules. Food had no effect on the absorption of amlodipine, bepridil, diltiazem, isradipine, or verapamil in the studies cited. 

The increase in bioavailability of manidipine in the presence of food may be because it is lipophilic and solubilised by food and bile secretions. Other lipophilic dihydropyridine calcium-channel blockers include felodipine and nisoldipine. Food may alter the release characteristics of modified-release preparations of drugs, increasing the rate of absorption of the drug, and thereby potentially increasing effects. 

Solid oral dosage forms can be modified in various ways to alter the release profile of the active substance. Preparations with such an altered release profile are called modified-release preparations. Some of the reasons have been presented previously (Sect. 4.9.1). 

Modified-release preparations are discussed for several reasons. At first, a pharmacist should know that such modifications on active substance release exist, and that he may dispense medicines with a specific release profile. Secondly, some active substances are only available as a modified-release preparation. Thirdly, the administration of a modified active substance release profile fi-om a tablet might be due to the properties of the active substance. These are some aspects that must be considered before such a tablet is crushed or a capsule is emptied. Enteric-coated tablets and capsules are not described as modified release preparations in the Ph. Eur. [6] but the same care must be taken not to damage the coat when using it for the preparation of other dosage forms. 

However, these modification strategies may not be possible to apply to modified-release preparations. Questions such as the following should be answered is it possible to spht the dosage form without destroying its function Is it possible to mix the content of a capsule without grinding Can the dosage form be modified into a liquid preparation And if so, should the dose or dose frequency be adjusted ... 

A modified-release preparation should be administered as such to have its intended effect. Sphtting is not an option, unless this is provided by the manufacturer and is specified in the product details. Sometimes, asking the manufacturer may give the desired information, but not aU manufacturers are able or willing to help with the particular situation of an individual patient. 

A graph of the release profile in the product details would also benefit the application of modified-release preparations, as well as information on the dependence on physiological and anatomical factors. 

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