کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2085566 1545381 2010 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fusion production of solid dispersions containing a heat-sensitive active ingredient by hot melt extrusion and Kinetisol® dispersing
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Fusion production of solid dispersions containing a heat-sensitive active ingredient by hot melt extrusion and Kinetisol® dispersing
چکیده انگلیسی

Many techniques for the production of solid dispersions rely on elevated temperatures and prolonged material residence times, which can result in decomposition of temperature-sensitive components. In this study, hydrocortisone was used as a model temperature-sensitive active ingredient to study the effect of formulation and processing techniques as well as to characterize the benefits of KinetiSol® Dispersing for the production of solid dispersions. Preformulation studies were conducted using differential scanning calorimetry and hot stage microscopy to identify optimum carriers for the production of amorphous solid dispersions. After identification, solid dispersions were prepared by hot melt extrusion and KinetiSol® Dispersing, with material characterized by X-ray diffraction, dissolution and potency testing to evaluate physicochemical properties. Results from the preformulation studies showed that vinylacetate:vinylpyrrolidone (PVPVA) copolymer allowed for hydrocortisone dissolution within the carrier at temperatures as low as 160 °C, while hydroxypropyl methylcellulose required temperatures upward of 180 °C to facilitate solubilization. Low substituted hydroxypropyl cellulose, a high glass transition temperature control, showed that the material was unable to solubilize hydrocortisone. Manufacturing process control studies using hot melt extruded compositions of hydrocortisone and PVPVA showed that increased temperatures and residence times negatively impacted product potency due to decomposition. Using KinetiSol® Dispersing to reduce residence time and to facilitate lower temperature processing, it was possible to produce solid dispersions with improved product potency. This study clearly demonstrated the importance of carrier selection to facilitate lower temperature processing, as well as the effect of residence time on product potency. Furthermore, KinetiSol® Dispersing provided significant advantages over hot melt extrusion due to the reduced residence times and lower required processing temperatures. This allowed for the production of solid dispersions with enhanced product potency.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 74, Issue 2, February 2010, Pages 340–351
نویسندگان
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