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Effective loading of incompatible drugs into nanosized vesicles: a strategy to allow concurrent administration of furosemide and midazolam in simulated clinical settings

مؤلف البحث
Heba A. Fathi , Carol Yousry , Mahmoud Elsabahy , Mahmoud El-Badry
تاريخ البحث
قسم البحث
مجلة البحث
International Journal of Pharmaceutics
الناشر
Elsevier
عدد البحث
( 636)
موقع البحث
journal homepage: www.elsevier.com/locate/ijpharm
سنة البحث
2023
صفحات البحث
(122852)
ملخص البحث

The current study aims to assess the use of nanocarriers to limit drug incompatibilities in clinical settings, and thus eliminating serious clinical consequences (e.g., catheter obstruction and embolism), and enhancing in vivo bioavailability and efficacy. As a proof-of-concept, the impact of loading well-documented physically incompatible drugs (i.e., furosemide and midazolam) into nanosized vesicles on in vitro stability and in vivo bioavailability of the two drugs was investigated. Furosemide and midazolam were loaded into nanosized spherical vesicles at high entrapment efficiency (ca. 62–69%). The drug-loaded vesicles demonstrated a sustained drug release patterns, high physical stability and negligible hemolytic activity. Physical incompatibility was assessed by exploiting microscopic technique coupled with image processing and analysis, dynamic light scattering and laser Doppler anemometry. Incorporation of drugs separately inside the nanosized vesicles dramatically decreased size and number of the precipitated particles. In vivo, the niosomal drug mixture demonstrated a significant improvement in pharmacokinetic profiles of furosemide and midazolam compared to the mixed free drug solutions, as evidenced by their longer circulation half-lives and higher area under the plasmaconcentration time curves of both drugs. Nanocarriers could provide an auspicious strategy for circumventing drug incompatibilities, thus reducing adverse reactions, hospitalization period and improving therapeutic outcomes.