A Comparative In Vitro Assay of Drug Release Performance of Pyridostigmine Bromide Tablets

Myasthenia gravis is an autoimmune disease that destroys key components of the neuromuscular system. The most common therapy uses reversible inhibitors of cholinesterase activity, such as pyridostigmine bromide (PB). The nature of this illness implies that we must be sure that all available PB immediate-release tablets produce the same therapeutic response. The aim of this study was to analyze PB immediate-release formulations provided by pharmacies in MERCOSUR countries A, B, and C. The formulations, which were produced in different manufacturing plants of the same multinational company, were analyzed following USP 29 specifications. The products fulfilled the assay, uniformity of dosage units, and dissolution test in S2 stage. Dissolution profiles were carried out following EMEA and FDA regulations, and the similarity factor (f2) was applied to A and C but not B, as this one did not fulfill the dissolution requirements. Pyridostigmine bromide tablets from countries A and C are considered to be similar and could be interchangeable. Formulation B exhibited such different dissolution behavior that its interchangeability is discouraged, as well as its introduction in countries A and C from the manufacturing country B. The difference in dissolution was a concern in light of the commercial need to manufacture the product in different manufacturing plants worldwide using excipients, equipment, and processes from local sources. In vitro dissolution testing plays an important role in detecting such differences. Therefore, an investigation was conducted to determine if there are differences in the dissolution profiles of PB (60 mg) immediate-release tablets from countries A, B, and C within MERCOSUR (South Common Market). The first purpose of this study was to assure that these products fulfill the same quality standards. But the most important objective was to evaluate the feasibility of product interchange from bordering countries A, B, and C, taking into account that they belong to the same Common Market where free trading is possible. It is important to emphasize that the formulation from country B has a much lower price than those from A or C, so importation is possible for economic reasons. This type of study is not often performed because most products manufactured by the same company in different plants do not have as demanding a dosage as PB tablets, so their interchangeability would not be a topic of major concern. MATERIALS AND METHODS Chemicals Analytical grade phosphoric acid, glacial acetic acid, and potassium chloride, and HPLC grade acetonitrile and Corresponding author. diss-14-04-06.indd 33 11/8/2007 1:59:03 PM dx.doi.org/10.14227/DT140407P33