Bioequivalence of Sandoz methylphenidate osmotic‐controlled release tablet with Concerta^® (Janssen‐Cilag)

The aim was to assess the bioequivalence of Sandoz methylphenidate osmotic‐controlled release (OCR) tablets (Sandoz [Methylphenidate] MPH OCR) with Concerta^®, a methylphenidate formulation indicated for the treatment of attention deficit/hyperactivity disorder (ADHD). Four open‐label, randomized, single‐dose, two‐way crossover bioequivalence studies were conducted in healthy subjects: three fasting studies with 54‐, 36‐ and 18‐mg doses of methylphenidate, and one fed study with the 54‐mg dose. The d‐ and l‐threo‐methylphenidate plasma levels were quantified using liquid chromatographic methods with tandem mass spectrometry (LC MS/MS). Bioequivalence of the formulations was accepted if the 90% geometric confidence intervals of the ratio of least‐squares means of Sandoz MPH OCR to Concerta^® of ln‐transformed area under the curve (AUC_0–t) and C_max were within the acceptance range of 80–125%. All studies met the bioequivalence criteria, and 90% geometric confidence intervals for AUC_0–t and C_max were within the predefined range. All plasma concentration time curves for Sandoz MPH OCR under fasting conditions showed a biphasic profile comparable with Concerta^®, confirmed by bioequivalence of the partial metrics AUC_0–2h, AUC_2‐24 h, C_{max(0–2 h)} and C_{max(2–24 h)}. Both products were well tolerated and no relevant differences in the safety profiles were observed. It was concluded that Sandoz MPH OCR is bioequivalent to Concerta^® in terms of rate and extent of absorption when administered as a single dose of one extended‐release tablet of 54, 36, or 18 mg under fasting conditions and at a dose of 54 mg under fed conditions.

DOI: 10.1002/prp2.72

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