Introduction:

Paxiflas(r) is the combination of tramadol HCl/paracetamol (37.5/325 mg) in fast disintegrating tablets (FDTs), commercialized by Laboratorios Gebro Pharma S.A. The FDTs are intended to be placed in the mouth, where they are rapidly disintegrated without the need of water. They are aimed to active patients who do not have access to drinking water all the time, busy individuals, or those who travel frequently. Moreover, they are especially indicated for individuals with difficulties in swallowing and the elderly and help to improve therapeutic compliance. In addition, the combination combines the rapid action of paracetamol with the longer action of tramadol hydrochloride.

Objectives:

To demonstrate the bioequivalence between Paxiflas(r), administered with or without water, and tablets of the reference product, Zaldiar(r), administered with water, in healthy subjects under fasting conditions.

Material and methods:

Open label, balanced, randomized, crossover, single oral dose, 3 treatment, 3 period, 3 sequence, with a washout period of 7 days for subsequent period I and II, and 8 days for period II and III. Subjects were randomized to receive single oral dose (2 tablets) of Paxiflas(r), administered without water (product A) or with water (product B), and Zaldiar(r) with water. Bioequivalence was considered if the 90 % confidence interval (90 % CI) of geometric mean ratio of Cmax and AUC0-t between test and reference product fell within the range of 80-125 % for (+) tramadol, (-) tramadol, and paracetamol. The secondary objective was to monitor the safety and tolerability of products A and B.

Results:

Bioequivalence was evaluated in 38 subjects for product A and in 39 subjects for product B. Optimal plasma concentration levels of (+) tramadol were achieved at 0.75-3 h for product A, at 0.5-4 h for product B, and at 0.5-3 h for reference product. In the case of (-) tramadol, plasma levels were achieved at 0.75-3 h for product A, at 0.5-4 h for product B, and at 0.5-3 h for reference product. Finally, plasma levels of paracetamol were achieved at 0.25-2.5 h for the product A, at 0.5-2 h for product B, and at 0.25-2.5 h for reference product. Bioequivalence (90 % CI lying within the acceptable range of 80.00-125.00 %) was met in 38 subjects receiving product A and 39 subjects receiving product B. Tramadol HCl/paracetamol FDTs were well tolerated. A total of 6 adverse events (AEs) were reported during the study (headache, giddiness, pain in abdomen, itching on forearms and thighs, and elevated eosinophil count), of which 3 were expected and possibly related to the study product. The AEs were mild to moderate in severity. No serious AE was observed during the study.

Discussion:

Data from the present study demonstrate the bioequivalence between Paxiflas(r) FDTs, administered with and without water in different periods, and tablets of Zaldiar(r), administered with water, in terms of rate and extent of absorption under fasting condition.

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