In vitro stability, potency, and dissolution of duloxetine enteric-coated pellets after exposure to applesauce, apple juice, and chocolate pudding.

BACKGROUND: Difficulty swallowing is a common problem in the clinical setting, particularly in elderly patients, and can significantly affect an individual's ability to maintain a proper level of nutrition. OBJECTIVE: The purpose of this in vitro study was to determine if mixing duloxetine enteric-coated pellets in food substances is an acceptable alternative method for administering this oral formulation to patients with swallowing difficulties. METHODS: To determine whether administration in food substances with varying pH values (applesauce and apple juice, pH = approximately 3.5; chocolate pudding, pH = approximately 5.5-6.0) affects the enteric coating of the formulation, duloxetine pellets (ie, the contents of a 20-mg duloxetine capsule) were exposed to applesauce, apple juice, and chocolate pudding at room temperature and tested in triplicate for potency and impurities; for dissolution, 6 replicates were tested. To assess product stability and integrity of the enteric coating, potency, impurities, and dissolution tests of the pellets were conducted and compared with pellets not exposed to food. The duloxetine pellets were extracted from the food material using a solution of 0.1 normal (N) hydrochloric acid (HCl) prepared from concentrated HCl (commercially available) and deionized water. For the potency and impurities tests, a 40:60 solution of acetonitrile and pH 8.0 phosphate buffer was used as the sample solvent to extract the active pharmaceutical ingredient from the formulation to prepare the samples for testing. The amount of active pharmaceutical ingredient released (in vitro dissolution) from the pellets after exposure to the food substances was determined using 2 media solutions, 0.1 N HCl followed by pH 6.8 phosphate buffer. Applesauce and chocolate pudding were selected as vehicles for oral administration, while apple juice was intended to be used as a wash for a nasogastric tube. RESULTS: Mean (SD) potency results for the 20-mg capsule strength were 20.256 (0.066), 20.222 (0.163), and 19.961 (0.668) mg/capsule for the comparator not exposed to food, the sample exposed to applesauce, and the sample exposed to apple juice, respectively. However, exposure to chocolate pudding altered the integrity of the pellet's enteric coating (mean [SD] potency results, 17.780 [1.605] mg/capsule). Results of impurities testing suggested that none of the test foods caused significant degradation of the drug product. Mean dissolution results found that after 2 hours in 0.1 N HCl, < or = 1% of duloxetine was released from the comparator and pellets exposed to applesauce and apple juice. However, the mean dissolution profile of the sample exposed to pudding reported near-total release (90%) after 2 hours in 0.1 N HCl during the gastric challenge portion of the dissolution test. CONCLUSIONS: Results from this study found that the enteric coating of duloxetine pellets mixed with applesauce or apple juice was not negatively affected. The pellets were stable at room temperature for < or = 2 hours and should quantitatively allow delivery of the full capsule dose, provided that the pellet integrity is maintained (ie, not crushed, chewed, or otherwise broken). Therefore, mixing duloxetine pellets with applesauce or apple juice appears to be an acceptable vehicle for administration. However, exposing the pellets to chocolate pudding damaged the pellets' enteric coating, suggesting that pudding may be an unacceptable vehicle for administration.

Effects of the antidepressant duloxetine on body weight: analyses of 10 clinical studies.

OBJECTIVE: To assess the effect of duloxetine, an inhibitor of serotonin and norepinephrine reup-take, on body weight of patients with major depressive disorder (MDD). METHOD: Body weight data were obtained from all 10 phase II and III registration studies of duloxetine in the treatment of MDD, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), performed by Eli Lilly and Company between February 1999 and July 2003. Both acute (8-9 weeks) and long-term (26, 34, and 52 weeks) studies were analyzed. RESULTS: In the acute placebo-controlled studies, duloxetine-treated patients had a mean change of -0.5 kg compared with a change of 0.2 kg for placebo-treated patients (p < .001); no consistent relationship between duloxetine dose and weight change was observed. In placebo-controlled studies including an active comparator arm, similar acute mean weight changes were seen in duloxetine-treated and fluoxetine-treated patients (-0.7 kg vs. -0.6 kg) and in duloxetine-treated and paroxetine-treated patients (-0.3 kg vs. -0.2 kg). During longer-term treatment (34 weeks), mean weight change in patients treated with duloxetine 40 mg b.i.d. was not significantly different from that seen in placebo-treated patients (0.7 kg vs. 0.1 kg), while patients treated with the higher duloxetine dose of 60 mg b.i.d. or with paroxetine gained significantly (p ≤?.05) more weight than placebo-treated patients (0.9 kg, 1.0 kg, and 0.1 kg, respectively). In a 52-week open-label study, duloxetine-treated patients had a mean weight gain of 1.1 kg at endpoint (p < .001). CONCLUSION: Duloxetine-treated patients experienced weight loss after short-term treatment, followed by modest weight gain on longer-term treatment. The size of the weight changes observed suggests that the antidepressant duloxetine has minimal effects on weight for the majority of patients.