Kinetics of Absorption of a New Once-a-Day Formulation of Theophylline in the Presence and Absence of Food

Acceleration of in vitro dissolution studies of sustained release dosage form of theophylline and in vitro–in vivo evaluations in terms of correlations

“…There are nearly 170 sustained release dosage forms used in therapy according to an electronic drug index (The internet drug index for prescription drugs 1995). Dissolution procedures of these dosage forms take generally 8-12 h. Moreover, the dissolution period may increase to 20, 30 h for ultra-sustained dosage forms (Harrison et al 1993;Karasulu et al 2003) and 1-5 months for some biodegradable implants containing antibiotics, antineoplastics, enzymes or antiinflammatories and etc. (Witt and Kissel 2001;Woo et al 2001;Zhang et al 2003).…”

“…The second aim was to establish correlations between (The internet drug index for prescription drugs 1995) in vitro dissolution profiles of sustained and accelerated releases and also between (Harrison et al 1993) these in vitro release profiles and in vivo plasma profiles of the rabbits which were administered the same dosage form. By performing these correlations, it was aimed to predict both the results of in vitro sustained release and in vivo release profiles.…”

Predicting Food Effects on Drug Release from Extended-Release Oral Dosage Forms Containing a Narrow Therapeutic Index Drug

“…It was shown that in many cases, drug release from various theophylline ER formulations could be influenced (either increased or decreased) by concomitant intake of food (1,3,(14)(15)(16)(17)(18). Although in maintenance therapy of chronic obstructive lung disease, most drugs are given in conjunction with food, the recent literature contains very few in vivo studies (1,5,13,(18)(19)(20) and next to no in vitro investigations (21) of the influence of food on the bioavailability of theophylline from ER formulations. Food intake can influence the rate of drug release from the dosage form, the rate of drug absorption, the amount of drug absorbed, or all of these parameters simultaneously.…”

“…In addition, there are many other reasons for negative food effects, such as adsorption to food contents, decreased luminal diffusivity due to an increase in viscosity in the upper GI tract, and changes in the absorption rate due to food-induced changes in GI-motility and passage time along the GI tract (16,24). The latter changes will most likely not have an impact on the absorption process itself but can result in a significant change in the maximal plasma concentration (C max ) and the time to maximal plasma concentration (t max ) (19). Overall, food-induced changes in the intraluminal milieu can result in an unexpected shift in plasma theophylline concentration.…”

“…However, the test conditions and specifications are extremely heterogeneous. Attempts to use compendial dissolution methods for predicting theophylline absorption from sustained-release dosage forms have been made (16,19,26,27). In most cases, the paddle or basket apparatus and simple aqueous buffers like 0.1 N hydrochloric acid or phosphate buffer have been used, and the researchers only took into account typical pH values in the fasted stomach and small intestine.…”