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European Journal of Pharmaceutics and... Sep 2019The effect of drug load and digestion on the solubilization and absorption of fenofibrate in self-nanoemulsifying drug delivery system (SNEDDS) was assessed in a...
The effect of drug load and digestion on the solubilization and absorption of fenofibrate in self-nanoemulsifying drug delivery system (SNEDDS) was assessed in a pharmacokinetic study in rats and in an in vitro lipolysis model. SNEDDS containing fenofibrate at 75% of equilibrium solubility (S), a super-saturated SNEDDS (super-SNEDDS) containing fenofibrate at 150% of S and a super-SNEDDS suspension containing fenofibrate at 100% of S and an additional 50% S fenofibrate suspended (150% of S in total) were used. To assess the effect of lipid digestion on fenofibrate absorption in rats and fenofibrate solubilization during in vitro lipolysis, the lipase inhibitor orlistat was added at 1% (w/w) to the SNEDDS, resulting in six different SNEDDS: SNEDDS, super-SNEDDS and super-SNEDDS suspension with and without orlistat 1% (w/w). In vivo, super-SNEDDS had a higher C and AUC compared to SNEDDS and super-SNEDDS suspension, both with and without orlistat. While orlistat did not affect fenofibrate absorption in SNEDDS and super-SNEDDS, an increase of T and AUC for super-SNEDDS suspension was found when orlistat was present. During in vitro lipolysis, the addition of orlistat decreased digestion and lowered drug precipitation. Super-SNEDDS showed significantly increased absorption in rats compared to SNEDDS and super-SNEDDS suspension and the inhibition of digestion resulted in prolonged and increased absorption for the super-SNEDDS suspension.
Topics: Administration, Oral; Animals; Drug Delivery Systems; Emulsions; Fenofibrate; Intestinal Absorption; Lipase; Lipolysis; Male; Nanoparticles; Rats; Rats, Sprague-Dawley; Solubility; Suspensions
PubMed: 31276759
DOI: 10.1016/j.ejpb.2019.07.002 -
Physical Review. E Dec 2022A two-dimensional Monte Carlo simulation of dead-end diafiltration of bidispersed particle suspensions was performed. The diafiltration process involves separation of...
A two-dimensional Monte Carlo simulation of dead-end diafiltration of bidispersed particle suspensions was performed. The diafiltration process involves separation of components based on their size by using a permeable membrane. The continuous model was applied to study separation of mixture of disks with diameter d and D (D>d). It was assumed that the membrane at the bottom was permeable to the particles of the smaller diameter d, and impermeable to the particles of the larger diameter D. The process of vertical filtration was accompanied by the simultaneous Brownian motion of the particles and downward movement of the piston. The mixtures with different numerical concentrations of particles, diameter ratio, and initial size of the systems in the vertical direction L_{y} have been studied. The time dependencies of the rejection coefficient k and relative height of suspension h/L_{y} revealed the presence of complete and incomplete separation regimes. The presence of filtration and diffusion-driven stratification of the disks in the vertical direction was observed. The phenomenon of incomplete separation was explained by the formation of an impenetrable barrier from larger particles at the bottom of the deposit.
Topics: Monte Carlo Method; Suspensions; Computer Simulation; Particle Size
PubMed: 36671101
DOI: 10.1103/PhysRevE.106.064610 -
International Journal of Pharmaceutical... 2021An oral liquid formulation of nadolol, which is required for administration to patients who cannot swallow intact tablets, is not commercially available. The objective...
An oral liquid formulation of nadolol, which is required for administration to patients who cannot swallow intact tablets, is not commercially available. The objective of this study was to evaluate the stability of nadolol 10 mg/mL prepared in Oral Mix vehicle and stored in amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride for 91 days at 4ÆC and 25ÆC; and polypropylene oral plastic syringes at 25ÆC only. Three separate batches of nadolol suspension 10 mg/mL were prepared with Oral Mix. Of the suspension, 50-mL aliquots were stored in 100-mL bottles (amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride). Half of the bottles from each container type were stored at 25ÆC and the other half at 4ÆC. On study days 0, 2, 7, 14, 21, 28, 42, 56, 72, and 91, nadolol concentration was determined using a reverse-phase, stability-indicating liquid chromatographic method from samples drawn from each type of container at each temperature. Oral syringes (3 mL), filled with 2 mL of suspension, were stored at 25ÆC and tested on days 0, 2, 7, 21, 42, and 91. The concentration of nadolol 10 mg/mL in Oral Mix in all study samples from bottles and oral syringes remained within 3.5% of the initial concentration. Based on the fastest degradation rate with 95% confidence, on day 91, between 99% to 100% and 98% to 100% remained in suspensions stored in bottles at 25ÆC and 4ÆC, respectively. Oral syringes at 25ÆC had 94% remaining on day 91. Multiple linear regression analysis demonstrated that the percent remaining was related to study day and container, but not temperature. On day 91, nadolol 10 mg/mL oral suspensions prepared with Oral Mix and stored in all bottle types at 4ÆC will retain more than 98% of the initial concentration compared to 99% at 25ÆC and only 94% when stored in oral syringes.
Topics: Administration, Oral; Chromatography, High Pressure Liquid; Drug Compounding; Drug Stability; Drug Storage; Humans; Nadolol; Plastics; Suspensions; Syringes
PubMed: 33798116
DOI: No ID Found -
Canister valve and actuator deposition in metered dose inhalers formulated with low-GWP propellants.International Journal of Pharmaceutics Dec 2023A challenge in pressurised metered-dose inhaler (pMDI) formulation design is management of adhesion of the drug to the canister wall, valve and actuator internal...
A challenge in pressurised metered-dose inhaler (pMDI) formulation design is management of adhesion of the drug to the canister wall, valve and actuator internal components and surfaces. Wall-material interactions differ between transparent vials used for visual inspection and metal canister pMDI systems. This is of particular concern for low greenhouse warming potential (GWP) formulations where propellant chemistry and solubility with many drugs are not well understood. In this study, we demonstrate a novel application of X-ray fluorescence spectroscopy using synchrotron radiation to assay the contents of surrogate solution and suspension pMDI formulations of potassium iodide and barium sulphate in propellants HFA134a, HFA152a and HFO1234ze(E) using aluminium canisters and standard components. Preliminary results indicate that through unit life drug distribution in the canister valve closure region and actuator can vary significantly with new propellants. For solution formulations HFO1234ze(E) propellant shows the greatest increase in local deposition inside the canister valve closure region as compared to HFA134a and HFA152a, with correspondingly reduced actuator deposition. This is likely driven by chemistry changes. For suspension formulations HFA152a shows the greatest differences, due to its low specific gravity. These changes must be taken into consideration in the development of products utilising low-GWP propellants.
Topics: Metered Dose Inhalers; Nebulizers and Vaporizers; Administration, Inhalation; Catheters; Aluminum; Suspensions; Aerosol Propellants; Hydrocarbons, Fluorinated
PubMed: 37925043
DOI: 10.1016/j.ijpharm.2023.123569 -
Chemosphere Mar 20222- Line ferrihydrite (Fh) is widely used as a robust amendment for rapid arsenic removal or remediation in water or soil. However, the poorly crystalline phase of Fh is...
2- Line ferrihydrite (Fh) is widely used as a robust amendment for rapid arsenic removal or remediation in water or soil. However, the poorly crystalline phase of Fh is unstable and leads to arsenic leaching after long-term submergence in reductive aquatic and soil environments. In this study, the synthesized As(V)-bound Fh was characterized by various spectral approaches to investigate the factors that may affect the variation in As(V)-Fh in long-term continuously submerged soil suspensions. The X-ray diffraction (XRD) results showed that hematite was the main product and that goethite was the byproduct after 360 d of incubation. Approximately 12-17% and 4-5% Fh were transformed at As/Fe mole ratios of 0.005 and 0.05, respectively. After 360 d of incubation, the hematite morphology was clearly observed by scanning electron microscopy (SEM), and the As(V)-Fh surface areas were also decreased by 17.3-27.6% and 11.9-16.6% for As/Fe mole ratios of 0.005 and 0.05, respectively. In a comparison of the two tested soils (soils sampled in Sichuan Province (SC) and Hunan Province (HN)), As(V)-Fh transformed faster in HN soil suspensions, and more hematite and goethite were formed. Furthermore, during the incubation period, As(V) was transformed to As(III), and both species were released into the suspension from the As(V)-Fh surface. It was suggested that soil pH and Fe(II) concentration were key factors controlling the As(V)-Fh transformation process, and the differences between the two soils were due to the different soil pH values and contents of available Fe. Arsenic release was mainly caused by Fh transformation and ligand competition with soil organic matter (SOM).
Topics: Arsenic; Arsenicals; Ferric Compounds; Soil; Suspensions
PubMed: 34767854
DOI: 10.1016/j.chemosphere.2021.132844 -
Antimicrobial Agents and Chemotherapy Oct 2018Posaconazole is used for prophylaxis for invasive fungal infections (IFIs) among patients with hematologic malignancies. We compared the incidence of breakthrough IFIs...
Posaconazole is used for prophylaxis for invasive fungal infections (IFIs) among patients with hematologic malignancies. We compared the incidence of breakthrough IFIs and early discontinuation between patients receiving delayed-release tablet and oral suspension formulations of posaconazole. This was a retrospective cohort study of patients receiving posaconazole between 1 January 2010 and 30 June 2016. We defined probable or proven breakthrough IFIs using the European Organization for Research and Treatment of Cancer (EORTC) criteria. Overall, 547 patients received 860 courses of posaconazole (53% received the oral suspension and 48% received the tablet); primary indications for prophylaxis were acute myeloid leukemia (69%), graft-versus-host disease (18%), and myelodysplastic syndrome (3%). There were no significant differences in demographics or indications between patients receiving the different formulations. The incidence and incidence rate of probable or proven IFIs were 1.6% and 3.2 per 10,000 posaconazole days, respectively. There was no significant difference in the rate of IFIs between suspension courses (2.8 per 10,000 posaconazole days) and tablet courses (3.7 per 10,000 posaconazole days) (rate ratio = 0.8, 95% confidence interval [CI] = 0.3 to 2.3). Of the 14 proven or probable cases of IFI, 8/14 had posaconazole serum concentrations measured, and the concentrations in 7/8 were above 0.7 μg/ml. Posaconazole was discontinued early in 15.5% of courses; however, the frequency of discontinuation was also not significantly different between the tablet (16.5%) and oral suspension (14.6%) formulations (95% CI for difference = -0.13 to 0.06). In conclusion, the incidence of breakthrough IFIs was low among patients receiving posaconazole prophylaxis and not significantly different between patients receiving the tablet formulation and those receiving the oral suspension formulation.
Topics: Administration, Oral; Aged; Antifungal Agents; Female; Humans; Invasive Fungal Infections; Male; Middle Aged; Retrospective Studies; Suspensions; Triazoles
PubMed: 30012757
DOI: 10.1128/AAC.00893-18 -
International Journal of Pharmaceutics Oct 2020The quality of an ophthalmic suspension is crucial for its in vivo performance, and often impact product's effectiveness. An in-depth understanding of critical quality...
The quality of an ophthalmic suspension is crucial for its in vivo performance, and often impact product's effectiveness. An in-depth understanding of critical quality attributes (CQAs) of ophthalmic suspensions such as particle size distribution (PSD) and rheology, as well as the impact of these CQAs on product performance are important for successful product development, quality control, and regulatory approval. This study employed brinzolamide ophthalmic suspension, 1%, as a model ophthalmic product, and six batches were manufactured using an innovative planetary centrifugal milling (PCM) process. Three batches were manufactured to have distinctly different PSD. These three batches had qualitatively (Q1) and quantitatively (Q2) the same composition as the model drug product (i.e., Azopt), while the differences in PSD were introduced by changing only the manufacturing process parameters. On the other hand, changes in rheology were introduced by altering the input level of the viscosity enhancing polymer in the formulation. A systematic approach was employed to understand the relation between manufacturing process parameters, CQAs, and in vitro product performance. Among the evaluated CQAs, PSD, rheology, surface tension, and drug dissolution were found more sensitive to the changes in the manufacturing processes. Most notably, we developed a rapid dissolution method (completed within minutes) employing in-situ fiber optic UV dissolution system. This novel dissolution method mimics the environmental conditions of the eye such as dissolution under "non-sink" condition and under high shear (from blinking). The method was highly discriminatory to differences in the PSD in the suspension. This study also revealed an important relation between the PSD of the suspension and its rheology which originated as a result of an interaction at the molecular level between the solid drug particles and the viscosity enhancing polymers. These findings underscore the need to evaluate CQAs of the ophthalmic suspensions in concert rather than separately when comparing ophthalmic drug products and product performance.
Topics: Particle Size; Solubility; Sulfonamides; Suspensions; Thiazines
PubMed: 32795488
DOI: 10.1016/j.ijpharm.2020.119761 -
Journal of the Royal Society, Interface Feb 2021Microscopic sessile suspension feeders live attached to surfaces and, by consuming bacteria-sized prey and by being consumed, they form an important part of aquatic...
Microscopic sessile suspension feeders live attached to surfaces and, by consuming bacteria-sized prey and by being consumed, they form an important part of aquatic ecosystems. Their environmental impact is mediated by their feeding rate, which depends on a self-generated feeding current. The feeding rate has been hypothesized to be limited by recirculating eddies that cause the organisms to feed from water that is depleted of food particles. However, those results considered organisms in still water, while ambient flow is often present in their natural habitats. We show, using a point-force model, that even very slow ambient flow, with speed several orders of magnitude less than that of the self-generated feeding current, is sufficient to disrupt the eddies around perpendicular suspension feeders, providing a constant supply of food-rich water. However, the feeding rate decreases in external flow at a range of non-perpendicular orientations due to the formation of recirculation structures not seen in still water. We quantify the feeding flow and observe such recirculation experimentally for the suspension feeder in external flows typical of streams and rivers.
Topics: Ecosystem; Feeding Behavior; Suspensions
PubMed: 33622143
DOI: 10.1098/rsif.2020.0953 -
Soft Matter Dec 2021Giant number fluctuations are often considered as a hallmark of the emergent nonequilibrium dynamics of active fluids. However, these anomalous density fluctuations have...
Giant number fluctuations are often considered as a hallmark of the emergent nonequilibrium dynamics of active fluids. However, these anomalous density fluctuations have only been reported experimentally in two-dimensional dry active systems heretofore. Here, we investigate density fluctuations of bulk suspensions, a paradigm of three-dimensional (3D) wet active fluids. Our experiments demonstrate the existence and quantify the scaling relation of giant number fluctuations in 3D bacterial suspensions. Surprisingly, the anomalous scaling persists at small scales in low-concentration suspensions well before the transition to active turbulence, reflecting the long-range nature of hydrodynamic interactions of 3D wet active fluids. To illustrate the origin of the density fluctuations, we measure the energy spectra of suspension flows and explore the density-energy coupling in both the steady and transient states of active turbulence. A scale-invariant density-independent correlation between density fluctuations and energy spectra is uncovered across a wide range of length scales. In addition, our experiments show that the energy spectra of bacterial turbulence exhibit the scaling of 3D active nematic fluids, challenging the common view of dense bacterial suspensions as active polar fluids.
Topics: Escherichia coli; Hydrodynamics; Suspensions
PubMed: 34787630
DOI: 10.1039/d1sm01183a -
Journal of Bioscience and Bioengineering Jul 2022Quantification of leuco-indigo is most important for Aizome, Japanese indigo-dyeing; however, there has been no convenient quantitative method. This study demonstrated...
Quantification of leuco-indigo is most important for Aizome, Japanese indigo-dyeing; however, there has been no convenient quantitative method. This study demonstrated that normal pulse voltammetry under quiescent conditions can be used to detect leuco-indigo. As a result of quantification of leuco-indigo in the depth direction in fermenting suspensions, the steady-state concentrations of leuco-indigo showed sigmoidal profiles in the depth direction. The steady state is caused by competitive reactions of microbial reduction of indigo and autoxidation of leuco-indigo by O dissolved from the air interface of the suspension. In addition, we investigated the effects of stirring the suspension and adding some nutrients to the concentration profile. The weakened activity was partially recovered by the addition of ethanol and remarkably recovered by the addition of hipolypepton or glucose. Knowledge is essential for the proper management of indigo-dye-fermenting suspensions.
Topics: Coloring Agents; Indigo Carmine; Suspensions
PubMed: 35597724
DOI: 10.1016/j.jbiosc.2022.04.009