Differences in Powder Properties of Two 1,4-Dihydropyridine-Type Compounds Evaluated through Thermal Analysis

Abstract

The powder properties of two 1,4-dihydropyridine type compounds, manidipine dihydrochloride (Man) and benidipine hydrochloride (Ben), which possess similar physicochemical properties, were compared through thermal and mechanical analyses. Man and Ben were compressed with lactose monohydrate (Lac) and magnesium stearate (Mgst) at different compression forces. As an index, we focused on the onset temperatures of Lac dehydration during thermal analysis and plotted them against compression forces to evaluate the differences in powder properties between Man and Ben. To discuss in detail, the Lac ratio was selected as a formulation factor and compression speed as a process factor, which would be influenced to the onset temperature or its profile. It could be represented that Man was more adherent than Ben through thermal analysis by changing these critical factors, which were consistent with the results obtained through mechanical analysis.Key words compression; powder property; crystal water; thermal analysis; fragmentation 1,4-Dihydropyridine-type compounds such as nifedipine and nicardipine hydrochloride are frequently prescribed calcium channel antagonists with antihypertensive activity. Manidipine dihydrochloride (Man) and benidipine hydrochloride (Ben) have been shown to be more potent and longeracting than previous generations of 1,4-dihydropyridines. 1,2)In a generic company, a series of medicinal compounds with a similar structure are developed as generic products. Accordingly, an approach with which to compare powder properties with the information about the crystallinity is desirable for formulation and process studies. In some papers, compression properties have been discussed by analyzing compaction parameters.3-8) The information obtained from these studies is useful for formulation development with appropriate tablet hardness and forecasting tableting trouble (capping or sticking tendency) at a commercial scale. However, information about the crystallinity of the compressed materials has not been considered. A comparison of powder properties considering the crystallinity of the compressed materials through thermal analysis has not yet been conducted in the pharmaceutical field.In a series of our research, 9-13) it could be speculated that Man was more adherent than Ben through thermal analysis considering the crystallinity of compressed lactose (Lac) with different levels of particle size. The goals of this study are as follows: 1) To find critical factors other than Lac particle size for discussing the differences in powder properties between Man and Ben through thermal analysis. 2) To confirm the differences in powder properties between Man and Ben through mechanical analysis as we have speculated before. ExperimentalMaterials Man (Sanyo Chemical Laboratories Co., Ltd., Japan); Ben (Daito Pharmaceutical Co., Ltd., Japan); two types of Lac, Pharmatose ® 200M (DMV, the Netherlands), and Dilactose ® R (Freund Sangyo, Japan); and magnesium stearate (Mgst, Taihei Kagaku, Japan) were used for the preparatio...