Thursday, 21 August 2003
This presentation is part of : Thursday Poster Sessions

PD-053 A Novel Fast-Disintegrating Oral Formulation of the Atypical Antipsychotic Risperidone

Jacobo Mintzer1, Phillipe Lechat2, Bart M.M. Remmerie2, and Erik Mannaert2. (1) Medical University of South Carolina, Charleston, SC, USA, (2) Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium

Background: It is estimated that in 30-40% of elderly patients, difficulties with administration of oral tablets prevent them from receiving their medication as prescribed. This results in a high incidence in non-compliance and ineffective therapy, especially amongst patients suffering from psychiatric symptoms. In order to address this, a fast-disintegrating oral formulation of risperidone was developed, which starts to dissolve within seconds after placing on the tongue. Risperidone is an atypical antipsychotic, which is usually prescribed in oral tablet formulation.

Objective: To compare the pharmacokinetic properties of risperidone fast-disintegrating oral formulation with those of risperidone oral tablets.

Materials and Methods: Two, Phase I, open-label, single-dose, randomized, two-way crossover trials were conducted in young healthy volunteers to assess bioequivalence of the two formulations. In the first trial, 1mg of risperidone (administered as 2x0.5mg oral tablets) was compared to 2x the 0.5mg risperidone fast disintegrating oral formulation (N=50). A second trial compared the 2mg formulations (N=40). Pharmacokinetic parameters included maximal plasma concentration (Cmax), time to reach the maximal plasma concentration (tmax), plasma elimination half-life (t1/2) and area under the curve (AUC¥). Relative bioequivalence of the fast-disintegrating formulation versus the standard oral tablet formulation (Frel: range 80%-125%) was tested using 90% Confidence Intervals of Cmax and AUC¥ log-transformed ratios.

Results: The plasma concentration-time profiles of the active moiety (i.e., the sum of risperidone and its pharmacologically equipotent metabolite 9-hydroxy-risperidone) were similar for both formulations at each dose. Maximum plasma concentrations were comparable between the 2x0.5mg fast-disintegrating and standard oral tablet formulations (N=37; Cmax: 12.64.1 and 13.73.9 ng/ml, respectively) and between the 2 mg formulations (N=38; Cmax: 23.26.50 and 25.37.84 ng/ml, respectively). AUC¥, tmax and t1/2 were similar for both formulations at each of the investigated dosages. Frel values for both formulations were contained within the bioequivalence range for Cmax [2x0.5mg: 90.1% (84.1-96.5); 2mg: 92.1% (87.5-96.9)] and AUC¥ [2x0.5 mg: 97.2 (91.2-103.6); 2mg: 98.0% (94.2-101.9)]. Adverse events, when they occurred, were mild and were similar between the two formulations.

Discussion: Risperidone fast-disintegrating oral formulation is bioequivalent with oral risperidone tablets in healthy young volunteers. While it is well accepted that bioequivalence is established in healthy adults, conclusions apply to all patient populations, including children and elderly. This fast-disintegrating oral formulation may be beneficial particularly in patients who have difficulties swallowing or who evade swallowing. Expected benefits are improved adherence to and compliance with therapy.

Conclusion: Oral fast-disintegrating risperidone is bioequivalent with risperidone in tablet formulation, and may present a convenient and patient-friendly alternative.

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