کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2084346 1545388 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dissolution-modulating mechanism of alkalizers and polymers in a nanoemulsifying solid dispersion containing ionizable and poorly water-soluble drug
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Dissolution-modulating mechanism of alkalizers and polymers in a nanoemulsifying solid dispersion containing ionizable and poorly water-soluble drug
چکیده انگلیسی

We investigated the dissolution-modulating mechanism of alkalizers and polymers in nanoemulsifying Gelucire 44/14 (GUC)-based solid dispersions (SDs) for controlled release. Aceclofenac (AFC), an ionizable and poorly water-soluble drug, was chosen because of its extremely low solubility at low pH. Nanoemulsifying SD systems containing alkalizers and/or polymers were prepared by the melting method. Drug crystallinity, microenvironmental pH (pHM), dissolution rate, and droplet size in the media from nanoemulsifying SD were then characterized. Ternary SD containing alkalizers, mainly Na2CO3 and NaHCO3, enhanced the initial release rate of AFC in simulated gastric fluid (pH 1.2), but resulted in spring-like precipitation. However, adding a secondary polymer, Poloxamer 407, prevented precipitation in the quaternary SD system. Poloxamer 407 and alkalizer (Na2CO3) facilitated nanoemulsion formation (80–140 nm) with a smaller droplet size in a medium of pH 1.2 as visualized by TEM. The surface and inner pHM were also modulated by the alkalizers, but not by the polymers. The drug’s crystalline structure was further changed to partially or almost amorphous form by the alkalizers and polymers in SD as characterized by instrumental analysis. The synergistic effects of alkalizers and secondary polymers in SD on reduction of drug crystallinity and modulation of pHM via molecular interactions could modulate dissolution rates of ionizable and poorly water-soluble model drug without spring-like precipitation by providing more favorable nanoemulsion-forming environment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 72, Issue 1, May 2009, Pages 83–90
نویسندگان
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