Dalla specialità medicinale al farmaco generico: sviluppo di farmaci bioequivalenti

Abstract

Two medicinal products containing the same active substances are considered bioequivalent if they are pharmaceutically equivalent, they have the same bioavailability and comparable plasmatic curve. Sometimes bioequivalence can be investigated with in vitro-studies, like dissolution test. The BCS (Biopharmaceutics Classification System)-based biowaiver approach is useful to reduce in vivo bioequivalence studies, it may represent a “surrogate” for in vivo bioequivalence. This concept is applicable to immediate release and solid pharmaceutical products for oral administration and systemic action having the same pharmaceutical form. BCS-based biowaivers are applicable to substances with “high solubility” and “high permeability” (BCS-class I) like Enrofloxacin and Metronidazole, or “high solubility” and “low permeability” (BCS-class III) like Spiramycin. The objective of this research work was to develop two new products "comparable" and "alternative" respect to the products already on the market. In the first project, conventional release tablets of "Spiramycin" and “Metronidazole” were developed in two different doses, equivalent to a veterinary medicinal product on the market. In the second project, conventional release tablets of "Enrofloxacin" were developed in two different doses, equivalent to a veterinary medicinal product on the market. Bioequivalence studies were conducted using BCS-based biowaivers approach. Both projects are divided into different steps: formulation development, development and validation of analytical method, and bioequivalence in vitro-study. Bioequivalence between “new” and “originator” product has been demonstrated using the dissolution tests and comparing the dissolution curves. Active ingredients are rapidly and equally released by the two formulations at all pH values. The analysis of variance carried out by applying the two-way ANOVA test shows that the effect of the composition of the product is not significant, while the effect of the time is highly significant. “Developed” and “originator” products are pharmaceutically equivalent and bioequivalent, so they can be considered therapeutically equivalent.