کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5547677 1556149 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effect of cyclophosphamide on the solid form of mannitol during lyophilization
ترجمه فارسی عنوان
اثر سیکلوفسفامید بر روی فرم جامد مانیتول در طی لیووفیلیزاسیون
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی

Mannitol is a commonly used bulking agent in lyophilized formulations. It can crystallize into multiple solid forms during lyophilization thereby exhibiting phase heterogeneity and variability in product performance. In this manuscript, we studied the effect of cyclophosphamide (CPA), an anticancer drug, on the solid form of mannitol during lyophilization from aqueous solutions. Freeze-concentration studies were performed in the DSC while lyophilization was performed in a lab scale freeze dryer.DSC experiments revealed two-stage crystallization of mannitol (1.5% w/v) during freeze-concentration, evident as two distinct exothermic events (at − 18.2 °C and − 30 °C) in the cooling curve. This was complemented by two eutectic melting endotherms in the subsequent heating curve. Addition of CPA (4.0% w/v) completely inhibited the exotherm at − 18.2 °C, but enhanced the enthalpy of exotherm at − 30 °C by five folds. Likewise, only one eutectic melting endotherm was observed in the subsequent heating curve. Lyophilization of the solution containing only mannitol, yielded a mixture of β- (major) and δ- (minor) polymorphs of mannitol. However, in the presence of CPA, only δ-polymorph was observed in the lyophilized sample.This selective favoring of the metastable δ-polymorph over the stable β-polymorph, was explained by altered freezing kinetics of the solution in presence of CPA. The study provides mechanistic insights into solute crystallization behaviour during lyophilization of multi-component systems.

The purpose of this work was to evaluate the effect of cyclophosphamide, an anticancer drug, on the solid form of mannitol, a commonly used bulking agent, in frozen solution and in the lyophilized product. Cyclophosphamide selectively favored the metastable δ-polymorph of mannitol during lyophilization, by altering the freezing kinetics of the solution.183

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 101, 1 April 2017, Pages 251-257
نویسندگان
, , ,