Esophageal transit of risedronate cellulose-coated tablet and gelatin capsule formulations.

Risedronate sodium is an orally active antiresorptive agent and a member of the pyridinyl class of bisphosphonates. It has been approved for the treatment of Paget's disease of the bone and is under development as a chronic therapy for the treatment and prevention of osteoporosis. A novel cellulose film-coated tablet formulation was developed to optimize esophageal transit of this bisphosphonate. The aim of the present study was to compare the esophageal transit of the film-coated tablet formulation of risedronate with its original gelatin capsule dose form. A total of 25 elderly, healthy volunteers (mean 66 years), who were dysphagia-free, participated in this randomized cross-over study. On separate occasions, volunteers swallowed radiolabeled placebo formulations with 50 ml water. Dynamic images with participants in a sitting position were recorded for 10 min using a gamma camera. Scintigraphic imaging showed a delay in esophageal transit (greater than 15 s) in 28% of patients in the capsule group but in none of the tablet group (P<0.05). The mean transit times of the capsules and tablets were 23.8 and 3.3 s, respectively. Esophageal transit of film-coated tablets was faster than gelatin capsules, suggesting that film-coated tablets would be the appropriate formulation for all pivotal trials with risedronate and for subsequent commercialization.

Impaired oesophageal transit of capsule versus tablet formulations in the elderly.

Drug induced oesophageal injury is an important and preventable cause of iatrogenic injury. In most cases the injury is considered to be due to mucosal contact from formulations lodged in the oesophagus. A scintigraphic study was performed comparing the oesophageal transit of enteric coated tablets with similar sized and shaped gelatin capsules, using a population of elderly healthy volunteers similar in age (50-79 years) to the population most likely to be receiving regular treatment. Twenty three volunteers injected the radiolabelled tablet or capsule with 50 ml of water while sitting on two separate occasions according to a randomisation schedule. Oesophageal transit was assessed by gamma scintigraphy. Gastric residence was also assessed in 11 of 23 subjects. While the tablet was readily cleared from the oesophagus, mean transit time 4.3 seconds (range 1.0-14.0), the capsule often showed a comparatively prolonged holdup, mean transit time 20.9 seconds (range 1.5-174.5). Ten of 11 tablets emptied from the stomach intact, while all 11 capsules broke up in the stomach. Gelatin capsules showed a clear tendency to remain within the oesophagus of healthy elderly volunteers, while similar sized enteric coated tablets did not. These studies show the importance of assessing oesophageal transit when designing the formulation of drugs with a potential for oesophageal injury.