RESUMO
Panama, like most Latin American countries, has insufficient regulatory safeguards to ensure the safety and efficacy of all pharmaceutical products in the market, a situation that results in a two-tier system, where affluent citizens can afford innovator products while poor citizens must consume 'generics' of uncertain quality. Given that one lot of each drug product is analyzed every five years during registration while commercial lots are not, and since most products are not bioequivalent but simply copies or similars, there is a concern that commercial and registration lots of these 'generics' may not be of the same quality. The objective of this study was to assess the ability of various in vitro quality control tests to detect difference among five amlodipine products available in the Panamanian market: four 'generics', made in various countries, and the innovator, made in Germany and used as reference listed drug in Panama (Pan-RLD). The innovator manufactured in the United States (US-RLD) was used to compare the two RLDs. The Content Uniformity test, 30-min Dissolution test and multiple-pH Dissolution Profiles did not show any difference among the products. However, the in vitro dissolution absorption system 1 (IDAS1) showed a statistically significant difference in the amount dissolved between Pan-RLD and three out of the four 'generics', and significantly lower permeated amount for all the 'generics' compared with Pan-RLD; only US-RLD was similar to Pan-RLD. Thus, IDAS1 showed promise as a potential tool that authorities in weakly regulated markets can use to monitor for possible lot-to-lot product changes, which can help improve the quality of pharmaceutical products available to their entire populations. The significance of the similarity between the innovators made in Germany and the United States and their difference from the 'generics' (manufactured in other countries) is not known but deserves investigation.
Assuntos
Anlodipino , Medicamentos Genéricos , Controle de Qualidade , Solubilidade , Equivalência Terapêutica , Estados UnidosRESUMO
While Health authorities in Panama strive to increase generic drug use to contain the rising costs of medicines, there is still hesitation to embrace generic drugs. Thus, regulators and drug companies need to ensure the quality, safety and efficacy of generic drugs. One prevailing concern is the absence of control over lot-to-lot changes, which may impact consistent therapeutic performance. The objective of this work was to determine whether near-infrared spectroscopy (NIR) could detect product changes. Calibration models were built using reference (standard) tablets of two products: Virax® (200 mg acyclovir) and Amlopin® (5 mg amlodipine). Then, to assess the sensitivity of NIR to product changes we compared reference versus deliberately-modified formulations of these products. Comparisons were made using principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) of NIR spectra. Several modified lots were different from reference lots, and 3D score plots showed greater discrimination by PLS-DA than PCA. The Kth nearest neighbor scores (KNN) of the modified batches were used to classify formulations as identical or not identical versus the reference. In addition, the differences detected by NIR were correlated with different in vitro dissolution and/or permeation in the in vitro dissolution absorption system 2 (IDAS2): NIR and IDAS2 yielded the same rank-order of difference for the modified lots tested. This study suggests that NIR and IDAS2 can help detect lots of generic drugs that differ from the reference lots. This strategy may help regulatory agencies in developing countries to safeguard patients against lot-to-lot changes in generic products.