No abstract

The Brazilian generic drugs policy was implemented in 1999 with the aim of stimulating competition in the market, improve the quality of drugs and improve the access of the population to drug treatment. The process of implementing this policy allowed the introduction and discussion of concepts that had never before been used in the context of drug registration in Brazil: bioavailability, bioequivalence, pharmaceutical equivalence, generic drugs, biopharmaceutical classification system, biowaiver. The present article provides definitions for these concepts in the context of Brazilian legislation as well as a historical and chronological description of the implementation of the generic drugs policy in Brazil, including a list of current generic drug legislation. This article contributes to the understanding of the Brazilian generic drugs policy and facilitates the search for information concerning the legal requirements for registration of drugs in Brazil.

Simple and sensitive methods using high-performance liquid chromatography-diode array detection (HPLC-DAD) and ultraviolet (UV)-spectrophotometry were developed and compared to quantify lychnopholide (LYC) in poly-ε-caprolactone nanocapsules and to study its release kinetics. Both methods were validated concerning their specificity, linearity, limits of detection and quantification, precision, accuracy and stability. HPLC-DAD analyses were conducted using an RP C18 column, isocratic elution with a methanol-water (60:40 v/v) mobile phase at 0.8 mL/min flow rate and detection at 265 nm. The linear response (r(2) > 0.999) was obtained within a concentration range of 2-25 µg/mL using HPLC-DAD and 5-40 µg/mL using spectrophotometry. Intra-day and inter-day precision were obtained with low relative standard deviation values. The accuracy of the methods was within the range 98-101% for HPLC-DAD and from 96-100% for UV-spectrophotometry. Both methods were suitable to be applied for the determination of drug loading percentage (>96%) and encapsulation efficiency (>90%). Furthermore, the sensitivity of HPLC-DAD method allows studies of LYC release/dissolution in sink conditions. LYC presented 100% dissolution after 24 h, whereas only 60% of LYC was released from the nanocapsule dosage form, with no burst effect. The methods fulfilled all validation parameters evaluated for LYC quantification in the polymeric nanocapsules and have proven to be accurate, selective and sensitive in the previously mentioned applications.

Fármacos contidos em formas farmacêuticas sólidas devem ter

ABSTRACTA combination of drugs in experimental chemotherapy of Chagas' disease may increase the effectiveness of treatment. To evaluate the possible mechanisms that influence the improvement of therapy, we investigated the pharmacokinetic interaction between benznidazole and itraconazole in a murine model treated orally with single doses of 5 mg of each compound separately or together. Blood samples from treated mice were collected at different intervals for 48 h, and a high-performance liquid chromatography (HPLC)-UV method was used to quantify both drugs in the plasma. A decrease of 1.5-fold in the maximum drug concentration in the plasma (Cmax) and an increase of 2.66-fold in the volume of distribution (V) and 7.5-fold in the elimination half-life (t1/2β) of benznidazole when coadministered with itraconazole were observed. The parameters area under the curve (AUC0-t), area under the curve extrapolated to infinity (AUC0-∞), time to maximum concentration of drug in serum (Tmax), and clearance (CL) for benznidazole were not significantly different in this therapeutic regime. None of the evaluated parameters for ITC demonstrated a significant difference between isolated and associated administration. These results suggest that the main effect of this interaction leads to accumulation of benznidazole in the biological system. This effect may contribute to the improved therapeutic efficacy of this combination of drugs, in addition to synergism of the different mechanisms of action of benznidazole and itraconazole againstTrypanosoma cruzi in vivo.