Effect of pH on the In Vitro Dissolution and In Vivo Absorption of Controlled-Release Theophylline in Dogs

Evaluation of Matrix Tablets Based on Eudragit®E100/Carbopol®971P Combinations for Controlled Release and Improved Compaction Properties of Water Soluble Model Drug Paracetamol

“…Sustained release dosage forms that release drug in a pHindependent manner are considered to be of specific value in the area of drug delivery. Such dosage forms offer the potential advantage of reduced variability of bioavailability of drugs that can result from the dependence of drug release in vivo on the variable pH of the gastrointestinal tract (7)(8)(9). Although certain hydrophilic swelling polymers have been explored to be used in matrices to control drug release (10,11), rarely did individual polymers sustain the drug release in a pHindependent fashion (4,5).…”

Gastric pH and Gastric Residence Time in Fasted and Fed Conscious Cynomolgus Monkeys Using the Bravo® pH System

“…Several studies have demonstrated that the bioavailability of drugs with pH-dependent solubility, dissolution or stability can be significantly affected by the gastric pH in both human and preclinical species (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Prolongation of GRT may also change the extent of absorption of compounds and controlled-released dosage forms where dissolution is the rate limiting step (12,13).…”

Microenvironmental pH Modulation Based Release Enhancement of a Weakly Basic Drug from Hydrophilic Matrices**This work was presented in-part at the 31st Annual Controlled Release Society meeting in Honolulu, Hawaii (June 2004).

“…pH‐dependent solubility characteristics of weakly basic drugs can possibly result in low and incomplete release of these drugs from sustained release (SR) hydrophilic matrices due to the exposure of these dosage forms to high pH milieu for the majority of their gastrointestinal transit time. Development of pH‐independent release systems for delivery of such drugs not only ensures high release throughout physiological pH, but also lowers intra‐ and inter‐patient variability in bioavailability 1–3. Though delivery systems for pH‐independent release of weakly acidic drugs have also been developed,4 the drop in aqueous solubility with increasing pH conditions poses a greater problem for basic drugs as the intestinal residence time of SR formulations is much longer than the gastric residence time.…”