Influence of dissolution rate and pH of oral medications on drug-induced esophageal injury

The in vitro dissolution time and pH were measured for 16 drug products in capsule or tablet form representative of oral medications known to cause esophageal injury. The test drugs included Vibramycin, Minocin, quinidine sulfate, Cleocin HCl, Indocin, Tolectin 200, ferrous sulfate, vitamin C, aspirin, Procardia, phenobarbital, Dilantin, Butazolidin, Noctec, K-Dur, and Quinaglute. Artificial saliva (10 mL) was placed in a small beaker along with a pH probe connected to a digital display pH meter and a strip-chart recorder. The salivary pH was measured at baseline and continuously during the dissolution of each test medication and the time taken for complete dissolution was recorded. This experiment was repeated six times for each drug. Baseline and final dissolution pH were compared statistically for differences using the Wilcoxon matched-pairs signed-ranks test. Significance was established at the 0.05 level. Only three medications tested (vitamin C, aspirin, and Dilantin) produced a dissolution pH outside the range of physiological esophageal pH values. Although the majority of the test drugs significantly altered the baseline pH, the final dissolution pH did not fall outside the physiologic range. Nine of the 16 test drugs dissolved completely within 10 minutes, whereas the remaining 7 drugs took 30 minutes or longer (up to 24 hours) to dissolve. We conclude that the dissolution pH of potentially caustic medications does not appear to be a primary mechanism of drug-induced esophageal injury, whereas a rapid dissolution rate may play an important role in the pathogenesis of the lesion.