Akademik Veri Yönetim Sistemi
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, cilt.112, 2025 (SCI-Expanded)
Purpose: The absorption and bioavailability of the loop diuretic furosemide (Biopharmaceutics Classification System (BCS) Class IV compound) is highly variable due to its poor solubility and permeability. Ongoing studies aim to reduce the dose and side effects of furosemide by addressing its solubility and permeability issues. The aim of the study is to increase permeability and solubility of furosemide by formulating nanosuspensions. Methods: Furosemide suspensions were prepared in distilled water using polyvinylpyrrolidone K 30 (PVPK30) and a PVPK30-polysorbate 80 (Tween 80) mixture. Nanosuspension formulations were prepared using three methods (Ultra Sonicator, Ultra Turrax, and ball milling) either alone or in combination (Ultra Sonicator+ball milling or Ultra Turrax+ball milling). Physicochemical properties of furosemide, PVPK30, Tween 80, physical mixtures and nanosuspensions were evaluated by Differential Scanning Calorimetry Analysis (DSC), X-ray and Fourier Transform Infrared Spectrometer (FT-IR) analyses. Caco-2 permeability of furosemide, physical mixtures and nanosuspensions was also determined. Results: FT-IR spectra of furosemide nanocrystals revealed no significant change in functional groups. X-ray diffraction pattern confirmed the crystalline structure of furosemide in nanocrystal formulations. Formulation F5 (2366 +/- 104.7 nm), prepared by ultrasonication, and formulation F11, prepared using a combination of ultrasonication and ball milling, both stabilized with PVPK30, gave the smallest particle size (2310 +/- 144.6 nm). The increase in solubility (52.9 mu g/ml) of F11 was remarkable, with a 44-fold increase at pH 1.2. Nanocrystal formulation containing Tween 80 and PVPK30 (F8) produced by ball milling showed approximately 8-fold increase in permeability (72.13 x 10_6 cm/s). All these findings demonstrate that combining ultrasonication and ball milling significantly increases the solubility of furosemide, while incorporation of Tween 80 significantly improves its permeability, highlighting the effectiveness of nanosuspension strategies in optimizing BCS Class IV drug delivery. Conclusion: Based on the results, it can be concluded that with a thorough understanding of all factors affecting the solubility-permeability interaction, such as excipients and preparation techniques, it is possible to develop orally administered formulations with high solubility and permeability even for BCS Class IV compounds.