Development and validation of a dissolution test with reversed-phase liquid chromatography analysis for rupatadine in tablet dosage forms

Abstract

Recebido em 23/11/09; aceito em 15/1/10; publicado na web em 3/5/10 A dissolution test for in vitro evaluation of tablet dosage forms containing 10 mg of rupatadine was developed and validated by RP-LC. A discriminatory dissolution method was established using apparatus paddle at a stirring rate of 50 rpm with 900 mL of deaerated 0.01 M hydrochloric acid. The proposed method was validated yielding acceptable results for the parameters evaluated, and was applied for the quality control analysis of rupatadine tablets, and to evaluate the formulation during an accelerated stability study. Moreover, quantitative analyses were also performed, to compare the applicability of the RP-LC and the LC-MS/MS methods.Keywords: rupatadine; dissolution test; RP-LC. INTRODUCTIONDissolution test has emerged in the pharmaceutical field as a very important tool to characterize drug product performance. Therefore the dissolution studies are used not only to assess batch-to-batch consistency of drug release from solid dosage forms, but they are also essential in several stages of formulation development, for screening and proper assessment of different formulations. Moreover, the in vitro dissolution studies are relevant to predict the in vivo performance of a drug release and have been used as a tool to estimate the bioavailability of the drug. [1][2][3][4][5][6] Rupatadine, chemically (8-chloro-6,11-dihydro-11-[1-[(5-methyl3-pyridinyl) methyl]-4-piperidinylidene]-5H-benzo [5,6]cyclohepta [1,2b]pyridine), is a new drug which represents a second generation of H 1 -antihistamine that inhibits both platelet activating factor (PAF) and histamine (H 1 ) effects, through its interaction with specific receptors. It is rapidly absorbed (Tmax = 0.75-1 h) after oral administration, and is subjected to extensive presystemic metabolism, with hepatic cytochrome P450 (CYP) 3A4 as the main enzyme involved in its biotransformation. Clinically is indicated for the management of diseases with allergic inflammatory conditions, such as seasonal and perennial rhinitis, and chronic urticaria. 7-9The literature describes validated liquid chromatography tandemmass spectrometry (LC-MS/MS) methods, with detection performed by positive atmospheric pressure chemical ionization (APCI) and gradient elution for LC analysis, for the simultaneous determination of rupatadine and its two active metabolites in human plasma after liquidliquid extraction and enzymatic hydrolysis, supporting pharmacokinetic studies.9-13 Moreover, sensitive isocratic LC-MS/MS methods with positive electrospray ionization (ESI) were developed and validated for the quantitation of rupatadine in human plasma without determination of the main active metabolites, 14 and with determination of the metabolite desloratadine.15 For the analysis of rupatadine in tablet dosage forms, a reversed-phase liquid chromatography (RP-LC) method was developed and validated over the concentration range of 0.5-400 µg/mL, using a C 18 analytical column and isocratic elution with UV detection at 242 nm. 16 Furthe...

Design of Experiments for the Establishment of the Dissolution Test Conditions of Rupatadine Fumarate 10 mg tablets

“…That behave is logical due to the fact that the active pharmaceutical ingredient is an acid salt or weak base salt. 8,10,11 Thus, since our formulation didn´t show a good dissolution in water, it was then decided to execute the DoE using mediums constituted by phosphate buffer pH 5 and by HCl 0.1 N of pH 1, to evaluate the performance of the proposed formulation in the dissolution test.…”

Development of a Stability-Indicating RP-HPLC Method for Determination of Rupatadine and its Degradation Products in Solid Oral Dosage Form

“…Few spectrophotometric methods are available for the determination of the RUPA assay [7–9]. Few RP-HPLC methods are available for the determination of the RUPA in vitro study [10, 11]. Some titration methods are available for the assay determination of RUPA [12, 13].…”

Estabelecimento de condições para ensaio de dissolução de cápsulas de cinarizina empregando planejamento fatorial

“…1 Desse modo, torna-se imperativo realizar estudos de dissolução in vitro, a fim de assegurar a liberação da substância ativa da forma farmacêutica, garantindo assim sua qualidade biofarmacêutica. [2][3][4] Dentre os produtos de liberação imediata, a cinarizina (Figura 1) tem sido amplamente manipulada no mercado brasileiro na forma de cápsulas. O fármaco é um vasodilatador periférico e cerebral, utilizado no tratamento de transtornos isquêmicos, encefálicos ou periféricos, particularmente em síndromes labirínticas.…”