Dissolution profiles of perindopril and indapamide in their fixed-dose formulations by a new HPLC method and different mathematical approaches

Abstract

A new HPLC method was introduced and validated for simultaneous determination of perindopril and indapamide. Validation procedure included specifi city, sensitivity, robustness, stability, linearity, precision and accuracy. The method was used for the dissolution test of perindopril and indapamide in three fi xed-dose formulations. The dissolution procedure was optimized using diff erent media, different pH of the buff er, surfactants, paddle speed and temperature. Similarity of dissolution profi les was estimated using diff erent model-independent and model-dependent methods and, additionally, by principal component analysis (PCA). Also, some kinetic models were checked for dissolved amounts of drugs as a function of time.Keywords: perindopril, indapamide, dissolution profi les, model-independent methods, model-dependent methods, PCA One example in the area of anti-hypertensive polytherapy is the use of an angiotensin converting enzyme inhibitor, e.g., perindopril, and a diuretic, e.g., indapamide (Fig. 1) in one fi xed-dose formulation (1).Bearing in mind previous reports concerning simultaneous determination of perindopril and indapamide, some spectrophotometric methods were developed (2-5). Also, a few HPLC methods were elaborated and validated in the range of offi cial requirements (5-9). However, none of the above methods was applied to the dissolution study of perindopril and indapamide in their fi xed-dose combinations.A dissolution test is necessary to control the product properties within a batch and between batches. It is also needed in bioequivalence studies where similarity of dissolution profi les between a test product and a reference product should be demonstrated (10).A wide range of methods are available for comparison of dissolution profi le data (11)(12)(13)(14). There are also offi cial recommendations in this area (15,16

Comparative Solid-State Stability of Perindopril Active Substance vs. Pharmaceutical Formulation

“…Literature data published in the field of solid-state characterization of PER is rather poor. Gumieniczek et al [ 21 ] studied the dissolution profile of PER, while Dorniani et al [ 22 ] reported the preparation and characterization of magnetic nanoparticles coated with chitosan-perindopril erbumine, including some data regarding their thermal stability and dissolution profile. Kinetic studies were carried out solely regarding the isomerization of PER in the condensed phase using dynamics chromatography [ 23 ], and the two degradation pathways in aqueous solutions [ 24 ].…”