Theophylline Sodium Glycinate

An experimental estimate of hydration number, NH, of glycine in aqueous solution is given by using the calorimetric methodology developed by us earlier, which is briefly reviewed. We found NH to be 7±0.6 for glycine presumably in the zwitter ion form, 10±1 for sodium glycinate, and 5±0.4 for glycine hydrochloride. Both glycine and sodium glycinate seem to work purely as a hydration center without altering the nature of the bulk H2O away from the hydration shell. Glycine hydrochloride, in addition to the role of hydration center, seems also to act as a typical hydrophilic species such as polyols, urea, or polyethylene glycols. Hence, the effect of the latter on H2O is of a long range, like other hydrophilic species.

Pharmacokinetics of a new sustained‐release formulation of theophylline sodium glycerinate in healthy subjects was studied. In this study, a new asymmetric dosage regimen was presented to achieve a better accordance with the chronotherapy of asthma. Each of 10 subjects was administered one tablet (equivalent to 0.1 g anhydrous theophylline) in the morning and four tablets in the evening for a consecutive 6 days and blood samples were collected at the predetermined time and analyzed by a validated HPLC method. This new regimen produced a steady and effective level of theophylline in plasma for the whole day, especially in the evening. A lower dose in the morning could reach the effective level (Cmin4.97 ± 1.60 µg/mL and Cmax10.68 ± 1.80 µg/mL over the a.m. dosing interval) and a higher dose in the evening did not result in toxic levels but led to a reasonable concentration range (Cmax9.72 ± 1.56 µg/mL over p.m. dosing interval), which could maintain a higher plasma theophylline concentration without the risk of serious adverse events and control asthmatic symptoms probably occurring during the night or early in the morning. The results suggested that the proposed asymmetric regimen was necessary, practicable and safe for twice daily sustained‐release tablets of theophylline sodium glycerinate and also provides the basis for the clinical dosage regimen of other theophylline formulated products. Copyright © 2003 John Wiley & Sons, Ltd.