Determination of the Intestinal Permeability of Rispiridone after oral intake of two immediate-release (IR) dosage forms

ONNAINTY RENEE; SCOLARI ROMINA; LONGHI MARCELA; GRANERO GLADYS

Simposio; Biowaivers 2015, Implementación de las bioexenciones basadas en el Sistema de Clasificación Biofarmacéutica; 2015

Objectives. This work aims to assess the intestinal permeability of risperidone after the intake of a test and branded reference immediate-release (IR) formulations in comparison with the pure drug.Materials and methods. A comparative study was carried out between two immediate-release (IR) dosage forms of risperidone: a reference product and a similar product in comparison with the pure drug. To study the drug permeability was employed the in situ single-pass intestinal perfusion (SPIP) technique in rat duodenum. Introduction. For the purposes of drug approval, the interchangeability of a generic drug and the corresponding brand-name drug is based on the criterion of ?essential similarity?, which requires that the generic drug have the same amount and type of active principle, the same route of administration, and the same therapeutic effectiveness as the original drug, as demonstrated by a bioequivalence study. However, bioequivalence and therapeutic effectiveness are not necessarily the same. Although many generic formulations are made by the same manufacturer as the brand-name drug, the excipients used may differ.Results. The effective drug permeability (Peff) results from the two IR dosage forms of risperidone and the free drug were: Peff (risperidone)= (8  1) x 10-5 cm/s, Peff (reference formulation): (8  1) x 10-5 cm/s and Peff (test formulation)= (6  1) x 10-5 cm/s. The differences in the obtained results can be caused by variations in the amount of excipients like sodium lauryl sulphate (SLS) that are able to inhibit the P-glycoprotein (P-gp), thus, reducing the oral permeability of risperidone, a dual P-gp and cytochrome P450 3A (CYP3A) enzyme.