Effect on dissolution from halving methylphenidate extended-release tablets.

Abstract

OBJECTIVE: To determine the effect on in vitro dissolution from cutting methylphenidate extended-release tablets in half. DESIGN: Ritalin-SR (Ciba Pharmaceutical Co.) and generic methylphenidate extended-release (MD Pharmaceutical Inc.) tablets were dissolved in water according to the method prescribed by the US Pharmacopeia under two conditions: whole and halved. Samples were collected at 15, 30, and 45 minutes and at 1, 2, 3, 3.5, 4, 5, 6, and 7 hours. Methylphenidate content was determined by HPLC. RESULTS: Halving the tablets caused a statistically significant increase in cumulative dissolution as early as 15 minutes. The difference in cumulative dissolution reached its maximum for both Ritalin-SR and generic methylphenidate extended-release tablets at 2 hours. At this time point, the percent dissolution of the whole versus halved tablets was 57% versus 74% (Ritalin-SR), respectively, and 49% versus 67% (generic), respectively. The dissolution profiles of halved and whole extended-release methylphenidate tablets were parallel from this point through the 7-hour collection period. At 7 hours, however, there was no difference in the cumulative dissolution of halved versus whole tablets. CONCLUSIONS: While statistical differences during in vitro dissolution do exist and pharmacokinetic ramifications have not yet been determined, the absolute differences in dissolution between halved and whole tablets are not great. Halving methylphenidate extended-release tablets may be a clinically acceptable means of achieving a small increment/decrement in dose without converting to a regular-release tablet.