Theophylline sustained-release products

Most medications have shorter half-lives in children than in adults, and therefore children may need sustained-release products to maintain serum concentrations in the therapeutic range. For example, a sustained-release theophylline product may be needed for a child with asthma. It may need to be administered every 8h to the child as compared to every 12 h for a healthy, non-smoking adult to maintain therapeutic serum concentrations. When choosing a sustained-release theophylline preparation for a child, it must be remembered that because of differences in release properties, theophylline sustained-release products are not interchangeable. A product selected for the pediatric asthma patient should be reliably absorbed with a minimal serum concentration variation and not a preparation that has exhibited a difference in bioavailability when administered with or without food.[ > - ]... 

Ingestion of sustained-release products is the most common route of both accidental and intentional exposure to theophylline. Theophylline is available in oral and intravenous dosage forms. Aminophylline is available in oral, rectal, and intravenous dosage forms. 

Polyvinyl acetate is described in the literature as a matrix former in theophylline sustained-release tablets obtained by hot-melt extrusion [646]. In a similar way spray-dried PVAc/Povidone can be applied for the production of tablets and pellets using its excellent flowability. In this case the pulverization of polyvinyl acetate by cryogenic grinding can be avoided and the mixture of the active ingredient with the excipients are applied directly to the melt extruder. 

Chow, A.T. Meek, P.D. Jusko, W.J. High-pressure liquid chromatographic assay of theophylline in dog feces fohowing oral administration of sustained-release products. J.Pharm.Sei., 1993, 82, 956-958 Abdel-Hay, M.H. el-Din, M.S. Abuiijeie, M.A. Simultaneous determination of theophylline and guai-phenesin by third-derivative ultraviolet spectrophotometry and high-performance liquid chromatography. Analyst, 1992, 117, 157-160... 

Methylxanthines are ineffective by aerosol and must be taken systemically (orally or IV). Sustained-release theophylline is the preferred oral preparation, whereas its complex with ethylenediamine (ammophylline) is the preferred parenteral product due to increased solubility. IV theophylline is also available. 

Theophylline administered in liquids or uncoated tablets is absorbed rapidly and completely. In the absence of food, solutions or uncoated tablets of theophylline produce maximal concentrations in plasma within 2 hours and maximal plasma concentrations are achieved within I hour. Numerous sustained-release preparations of theophylline are available, designed for dosing intervals of 8, 12, or 24 hours. There is marked interpatient variability in the rate and extent of absorption, and especially in the effect of food and time of administration on these parameters. Thus, it is necessary to avoid substituting one apparently similar product for another. 

Food ordinarily slows the rate of theophylline absorption but does not limit its extent. With sustained-release preparations, food may decrease the bioavailability of theophylline with some products but may increase it with others. Recumbency or sleep also may significantly reduce the rate or extent of absorption. These factors make it difficult to maintain relatively constant concentrations of theophylline in plasma throughout the day. Concentrations required to alleviate asthmatic symptoms do not remain constant, and the emphasis has shifted toward designing dosing regimens that ensure peak concentrations in the early morning hours, when symptoms frequently worsen. 

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