Multimetal organic frameworks as drug carriers: Aceclofenac as a drug candidate

Background: Multimetal organic frameworks (M-MOFs) were synthesized by including a second metal ion with the main base metal in the synthesis process to enhance their applications for drug delivery. Aceclofenac (ACF), a nonsteroidal anti-inflammatory analgesic drug of low aqueous solubility, was selected as a candidate for the drug delivery system Purpose: This study aimed to evaluate the loading capacity (LC) and entrapment efficiency (EE) percentages of multi-Material of Institute Lavoisier (MIL)-100(Fe) (M-MIL-100(Fe)) for ACF. Materials and methods: Hydrothermal synthesis procedure was used to prepare multi-MIL-100(Fe) samples (Zn I-MIL-100(Fe), Zn II-MIL-100(Fe), Ca I-MIL-100(Fe), Ca II-MIL-100-(Fe), Mg I-MIL-100(Fe), Mg II-MIL-100(Fe), Mn I-MIL-100(Fe), and Mn II-MIL-100(Fe)). The characterization of M-MIL-100(Fe) samples was evaluated by X-ray powder diffraction (XRD), Fourier transform infrared spectra, scanning electron microscope (SEM), TGA, and N2 adsorption isotherms. The LC of M-MIL-100(Fe) and EE of ACF were determined. Nuclear magnetic resonance (NMR) and zeta-potential analyses were employed to confirm qualitatively the drug loading within M-MIL-100(Fe). Results: The ACF LC of MIL-100(Fe) was 27%, whereas the LC of M-MIL-100(Fe) was significantly increased and ranged from 37% in Ca I-MIL-100(Fe) to about 57% and 59% in Mn II-MIL-100(Fe) and Zn II-MIL-100(Fe), respectively. The ACF@M-MOFs release profiles showed slow release rates in phosphate buffer solutions at pH 6.8 and 7.4 as compared to the ACF@MIL-100(Fe). Conclusion: Therefore, M-MOFs showed a significant potential as a carrier for drug delivery systems

Degradation of artesunate in aqueous solution

Artesunate, ART, is an antimalarial drug which is the only soluble artemisinin available on the market. ART has a low stability in aqueous solution. The degradation rate of ART in aqueous solution in a range of pH values (2.00-10.50) and selected IV fluids at 37 °C was studied. The temperature dependence was also investigated. High-performance liquid chromatography, HPLC, with detection at 210 nm was employed. There were significant effects on the rate degradation of ART according to the pH value employed and temperature. Shelf-lives of ART were 2.5, 1.2 and 1.0 h when reconstituted at 0.6 mg mL-1 in Hartman’s solution, 0.9% normal saline, and 5% glucose IV fluid at 37 °C respectively. The pH-rate profile demonstrated three general regions: decreased rate with pH fall to pH 7.50 followed by an increased rate. There was a combination of specific acid-base and carboxylate anion catalysis. Buffers may have a small effect on the degradation rates. The effect of ionic strength was slightly significant on the rat degradation of ART. A comparison in the rate degradation of ART with HPLC and LC-MS showed no significant difference in measured degradation rates.The effect of inclusion complexes of ART with hydroxypropyl-ß-cyclodextrin (HPß- CD) at selected pH values on the phase solubility profile and stability of ART in aqueous solution was studied. The phase solubility profile of the complex was classified as AL- type, indicating the formation of a 1:1 stoichiometric inclusion complex. A complex of ART with HP-ß-CD (272 mg mL-1) showed a 25-fold increase in solubility compared to ART at pH 3.00. Lineweaver-Burk plots were used to calculate the stability constants of the inclusion complexes (Kst) as well as the rate constants for degradation of the free and complexed drug. The stability constants Kst of the inclusion complexes were 83, 73 and 60 M-1 at pH 6.00, 7.00 and 8.00 respectively.The activation energies (Ea) were obtained from Arrhenius plots of degradation rate constants in the presence and absence of HP-ß-CD. The thermodynamic parameters of activation enthalpy and entropy were obtained from Eyring Equation. The activation energies in the absence and presence of HP-ß-CD were 93.4 and 95.8 Kjmol-1 respectively. The shelf-life of ART in the presence of HP-ß-CD was increased five-fold. The shelf-life of ART at the pH minimum (pH 6.50) was 10.6 h. Then it was improved in the presence of 108 mg mL-1 HP-ß-CD to 46 h

Metal organic frameworks as a drug delivery system for flurbiprofen

Background: Metal organic frameworks (MOFs) have attracted more attention in the last decade because of a suitable pore size, large surface area, and high pore volume. Developing biocompatible MOFs such as the MIL family as a drug delivery system is possible. Purpose: Flurbiprofen (FBP), a nonsteroidal anti-inflammatory agent, is practically insoluble in aqueous solution, and, therefore, needs suitable drug delivery systems. Different biocompatible MOFs such as Ca-MOF and Fe-MILs (53, 100, and 101) were synthesized and employ ed for FBP delivery. Patients and methods: A sample of 50 mg of each MOF was mixed and stirred for 24 h with 10 mL of 5 mg FBP in acetonitrile (40%) in a sealed container. The supernatant of the mixture after centrifuging was analyzed by high-performance liquid chromatography to determine the loaded quantity of FBP on the MOF. The overnight-dried solid material after centrifuging the mixture was analyzed for loading percent using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, nuclear magnetic resonance, and FBP release profile. Results: The loading values of FBP were achieved at 10.0%±1%, 20%±0.8%, 37%±2.3%, and 46%±3.1% on Ca-MOF, Fe-MIL-53, Fe-MIL-101, and Fe-MIL-100, respectively. The FBP release profiles were investigated in a phosphate buffer solution at pH 7.4. The total release of the FBP after 2 days was obtained at 72.9, 75.2, 78.3, and 90.3% for Ca-MOF, Fe-MIL-100, Fe-MIL-53, and Fe-MIL-101, respectively. Conclusion: The MOFs are shown to be a promising drug delivery option for FBP with a significant loading percent and relatively prolonged drug release. © 2017 AL Haydar et al