查看更多>>摘要：The article describes the preparation and characterization of binary mixtures of two antiandrogens used in prostate cancer treatment, i.e. flutamide (FL) and bicalutamide (BIC), as well as their ternary mixtures with either poly(methyl methacrylate-co-ethyl acrylate) (MMA/EA) or polyvinylpyrrolidone (PVP). The samples were converted into amorphous form to improve their water solubility and dissolution rate. Broadband dielectric spectroscopy and differential scanning calorimetry revealed that FL-BIC (65%) (w/w) does not tend to crystallize from the supercooled liquid state. We made the assumption that the drug-to-drug weight ratio should be maintained as in the case of monotherapy so we decided to investigate the system containing FL and BIC in 15:1 (w/w) ratio with 30% additive of polymers as stabilizers. Our research has shown that only in the case of the FL-BIC-PVP mixture the crystallization has been completely inhibited, both in glassy and supercooled liquid state, which was confirmed by X-ray diffraction studies. In addition, we performed solubility and dissolution rate tests, which showed a significant improvement in solubility of ternary system as compared to its crystalline counterpart. Enhanced physical stability and water solubility of the amorphous ternary system makes it promising for further studies.
查看更多>>摘要：Direct derivation (DD) is a novel Powder X-ray diffraction quantification method based on intensity-composition equation, which can determine the weight fraction of individual phases in a mixture of components by chemical formulas. The DD method was applied to determine crystallinity degree of binary mixtures containing amorphous hydroxypropyl methylcellulose and crystalline monohydrate alpha-lactose in weight percentage <= 15% w/w. Three different scenarios were considered: a) the unit cell parameters of the crystalline phases are available b) the unit cell parameters are unknown but the patterns of pure crystalline and amorphous references are available and c) only the mixtures' patterns are available. Relative errors in scenarios a and b were comparable and reasonable (<20%), while in c, the crystalline degree was clearly underestimated evidencing the importance of determining the maximum number of crystalline reflections This can be easily achieved when the unit cell parameters and/or the patterns of pure references are available. To simulate the quantification of high potent API, the method was evaluated considering the scenario b, in samples covered by Kapton (R) film as containment system. In this case, an accurate quantification was achieved by subtracting the film signal from the observed pattern.
NSTL
Elsevier