Tablets modified-release

Gotteries, J., Svenheden, A., Alpsten, M., Bake, B., Larsson, A. et al., Gastrointestinal transit of amoxicillin modified-release tablets and a placebo tablet including pharmacokinetic assessments of amoxicillin, Scand. J. Gastroenterol. 1996, 32, 49-53. 

Voltarol is a brand-name preparation for diclofenac (NSAID) and modified-release tablets are available in 75 mg and 100 mg strength. Nu-seals is a proprietary preparation of enteric-coated aspirin 75 mg. Fentanyl, co-codamol and Suboxone (buprenorphine and naloxone) consist of opioid drugs. 

For modified-release tablets, when the drug product is in the same dosage form but in a different strength, is proportionally similar in its active and inactive ingredients, and has the same drug release mechanism, an in vivo BE determination of one or more lower strengths can be waived based on dissolution profile comparisons, with an in vivo... 

Immediate Release and Modified Release Tablets and Capsules... 

A 32-year-old man took 50 modified-release tablets of lithium carbonate and arrived at the emergency services soon after ingestion. Gastric lavage yielded several tablet fragments. Associated with other supportive measures, his serum lithium concentration never exceeded 0.75 mmol/1. 

A 15-year-old woman intentionally took 10 modified-release tablets of diltiazem 200 mg. She developed hypertension, oliguria, pulmonary edema, and respiratory distress syndrome, and required mechanical ventilation for 3 days, besides intravenous calcium, dopamine, and noradrenaline. After 5 days in an intensive care unit, she was transferred to a psychiatric hospital in good physical condition (22). 

Although modified-release formulations seem to be better tolerated, this is almost certainly a reflection of their less complete absorption. Iron is best absorbed in the duodenum, and most of the iron in modified-release tablets is released only when the tablets reach the lower parts of the gastrointestinal tract (46). 

The suspension and modified-release tablets produce the usual pattern of adverse effects (SEDA-15,101), although an enteric-coated formulation of naproxen in patients... 

Nitrates can be administered by various routes. For example, glyceryl trinitrate is used not only as traditional sublingual tablets but also in the form of modified-release tablets, buccal tablets, aerosolized oral spray, intravenous injection, and topical ointment or skin patches for percutaneous absorption (23). These different formulations have been developed largely as a means of controlling the onset and duration of action of glyceryl trinitrate, since in conventional oral form its action is limited by marked hepatic first-pass metabolism. 

A 73-year-old man took an unknown number of theophylline modified-release tablets and furosemide 40 mg tablets. He developed a tachydysrhythmia, vomiting, and restlessness. His maximum theophylline concentration was 67 pg/ml and he had hypokalemia (2.8 mmol/1) and hyponatremia (123 mmol/1). The maximum creatine kinase activity was (32 mol/1 [sic]) and the serum myoglobin concentration was 3789 pg/l. He was treated with oral activated charcoal, continuous venovenous hemodialysis, intravenous potassium and sodium chloride, forced diuresis, and continuous intravenous meto-prolol, and survived without sequelae. 

The main use of ethylcellulose in oral formulations is as a hydrophobic coating agent for tablets and granules. Ethylcellulose coatings are used to modify the release of a drug, to mask an unpleasant taste, or to improve the stability of a formulation for example, where granules are coated with ethylcellulose to inhibit oxidation. Modified-release tablet formulations mav also be produced using ethylcellulose as a matrix former. " ... 

New specific functionality/delivery systems (e.g., immediate release tablet to modified release tablet). 

In addition, the pharmacist or pharmacy technician should be sure that the correct presentation of a particular drug is being supplied. Some drugs may be presented in a variety of different forms, for example, modified-release and non-modified-release, tablets and capsules, etc. Furthermore, as these different presentations may be produced by the same pharmaceutical manufacturing company, the packaging may appear very similar. 

Gastrointestinal transit of amoxicillin modified-release tablets and a placebo tablet including pharmacokinetic assessments of... 

New dosage forms include products of different administration route (e.g., oral, when the original new drag product was a parenteral), new specific functionality and delivery system (e.g., modified release tablet, when the original new drug product was an immediate release tablet), and different dosage forms of the same administration route (e.g., capsule to tablet, solution to suspension). 

Figure 10.2 Factor and design space for formulation of a modified release tablet,...

Sengel CT, Hascicek C, Gonul N. Development and in-vitro evaluation of modified release tablets including ethylcellulose microspheres loaded with diltiazem hydrochloride. Journal of Microencapsulation. March 2006 23(2) 135-152. PubMed PMID 16754371. 

Tablets are defined in the Ph. Eur. as solid preparations each containing a single dose of one or more active substances [6]. Tablets are prepared by compressing tmiform volumes of particles or by another suitable manufacturing technique, such as extmsion, moulding or freeze-drying (lyophilisation). The Ph. Eur. distinguishes various types of tablets the most important being uncoated tablets, coated tablets, effervescent tablets, dispersible tablets, gastro-resistant tablets and modified-release tablets.

Modified-release tablets are defined in the Ph. Eur. as preparations with a modified drug release rate, place, or time at which the active substance is released compared to standard tablets [6]. Modified-release tablets include prolonged-release, delayed-release and pulsatile-release tablets. 

The patient benefits from a less frequent dosing regimen, i.e. the release occurs over an extended period of time (e.g. clomipramine). Modified-release tablets or enteric-coating tablets do not release the active substance directly, but do so in a specific part of the gastro-intestinal tract, either delayed or with a specific release pattern. The release of these tablets is adjusted to therapeutic needs of the patient. 

Coated tablets, such as enteric-coated tablets, and modified-release tablets are better not split or pulverised, because their specific features may be lost. If it is absolutely necessary to break them then the pharmacist must know beforehand the implications on the stability of the medicine and on its therapeutic effect (see Sect. 4.9). A controlled-release tablet that has been split may overdose. Splitting may also expose the taste of the medicine, which had originally been masked in the coated tablet. Only standard, non-coated tablets shall readily be processed into a powder mixture. 

The properties of all excipients present in the tablet must be considered for their possible effects on the final preparation, such as weight variation, disintegration time, dissolution characteristics and in vivo performance. The lower the proportion of the active substance present in the mixture, the more difficult it is to achieve a sufficient homogeneity. In Sects. 4.9 and 4.10, the formulation of tablets and the possibilities to process coated or modified-release tablets in capsules are discussed. 

Modified release tablet Is designed to be swallowed whole... 

Formulation and preparation method of modified-release tablets is tuned to the desired release profile, and thus differ from conventional tablets. The complex nature of this for-muladcHi and preparation can only occur in large-scale industrial production. 

Not aU active substances are suitable for a modified-release tablet. In general, an enteric coating on an ordinary tablet requires no specific properties of the active substance. However, other types of modified-release may require certain pharmacokinetic properties ... 

If the active substance is not available as raw material it may be processed from oral solid dosage forms by adapting those. Not all solid dosage forms however are tit for such an operation. Tablets with a gastro-resistant coating or modified-release tablets should not be crushed unless the product information confirms its suitability, see further Sect. 4.10.7. 

Paliperidone, or 9-hydroxyrisperidone, is the major active metabolite of risperidone. It binds to both dopamine Dj and serotonin 5-HT2A receptors, and antagonism at these receptors is thought to account for its therapeutic activity in schizophrenia. It was approved by the US Food and Drug Administration in 2007 for acute and maintenance treatment of schizophrenia it is available in modified-release tablets. The available literature on the pharmacodynamics, pharmacokinetics, clinical efficacy, and tolerability of paliperidone has been extensively reviewed [101 ]. 

Lobo, M. Patel, J. Kamins, G. Francis, R. Breza, B. Jerzewski, R. Interaction of omapatrilat with FD C Blue No. 2 lake during dissolution of modified release tablets. Int. J. Pharm. 2007, 339, 168-174. 

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