Dissolution profiles of four carbamazepine immediate-release generic products (200 mg tablets) and the reference product Tegretol® were evaluated using the USP paddles method and an alternative method with the flow-through cell system, USP Apparatus 4. Under official conditions all products met the Q specification, dissolution profiles of generic products were similar to the dissolution profile of the reference product (f 2 > 50) and model-independent parameters showed non significant differences to the reference product except mean dissolution time for product A (p < 0.05). On the other hand, when the flow-through cell system was used, none of the products met the pharmacopeial specification at 15 min and product A did not reach dissolution criteria at 60 min, dissolution profiles of all generic products were not similar to the reference product profile (f 2 < 50) and all model-independent parameters showed significant differences compared to the reference product (p < 0.05). Weibull's model was more useful for adjusting the dissolution data of all products in both USP apparatuses and Td values showed significant differences compared to the reference product (p < 0.05) when USP Apparatus 4 was used. These results indicate that the proposed method, using the flow-through cell system, is more discriminative in evaluating both, rate and extent of carbamazepine dissolution process from immediate-release generic products.

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The purpose of the present study was to determine whether caffeine modifies the pharmacokinetics and pharmacodynamics of (S)-ketoprofen following oral administration in a gout-type pain model. 3.2 mg/kg of (S)-ketoprofen alone and combined with 17.8 mg/kg of caffeine were administered to Wistar rats and plasma levels were determined between 0.5 and 24.0 h. Additionally, antinociception was evaluated based on the protocol of the PIFIR (pain-induced functional impairment in the rat) model before blood sampling between 0.5 and 4.0 h. Significant differences in C_max, AUC_0-24, and AUC_0-∞ values were observed with caffeine administration (p < 0.05). Also, significant differences in E_max, T_max, and AUC_0-4 values were determined when comparing the treatments with and without caffeine (p < 0.05). By relating the pharmacokinetic and pharmacodynamic data, a counter-clockwise hysteresis loop was observed regardless of the administration of caffeine. When the relationship between AUCe and AUCp was fitted to the sigmoidal E_max model, a satisfactory correlation was found (R² > 0.99) as well as significant differences in E_max and EC₅₀ values (p < 0.05). With caffeine, E_max and EC₅₀ values changed by 489.5% and 695.4%, respectively. The combination studied represents a convenient alternative for the treatment of pain when considering the advantages offered by using drugs with different mechanisms of action.

The bioequivalence of three chemically equivalent paracetamolgeneric Mexican products (500 mg tablets) was evaluated in 12 healthy volunteersusing the American innovator product (Tylenol, McNeil, Fort Washington, PA),as the reference. Single oral doses of each product were administered at 1-weekintervals using a 4 × 4 Latin square design balanced for the first residualeffect. The total amount of paracetamol excreted in urine in 24 hr was takenas a measure of bioavailability. In addition, moment analysis was used toestimate in vitro mean dissolution time (MDT) from dissolution profiles obtainedfollowing the USP 23 dissolution test specified for paracetamol tablets andto estimate in vivo mean residence time (MRT) from urinary excretion data.Significant differences in the dissolution performance and in the cumulativeamount of paracetamol excreted in urine up to 24 hr were observed when thedata were analyzed by analysis of variance (ANOVA) (p<. 05). Classical and Westlake 90% confidence limits, as well as the two-sided t test proposed by Schuirmann, and the Anderson-Hauckpower analysis supported the final conclusion that only one of the three genericparacetamol products studied can be considered equivalent to the referenceproduct Tylenol. A linear correlation between in vitro MDT and in vivo MRTwas found.