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Bioavailability and Granule Properties
Published in Dilip M. Parikh, Handbook of Pharmaceutical Granulation Technology, 2021
Frequently, the rate-limiting step to drug absorption from the gastrointestinal tract is drug release and drug dissolution from the dosage form. Various drug dissolution models show that drug diffusivity, solubility in the gastrointestinal tract, the surface area of solid wetted by the luminal fluid, and the gastrointestinal fluid hydrodynamics all play critical roles in determining the in vivo dissolution rate. Solubility in the gastrointestinal fluid contents is determined by aqueous solubility, crystalline form, drug lipophilicity, solubilization, and pKa of a drug concerning the gastrointestinal pH profile. Therapeutic agents with aqueous solubilities lower than 100 µg/mL often present dissolution limitations to absorption. Therefore, any factor that influences drug dissolution will likely influence drug absorption and bioavailability. These factors may be broadly classified as physicochemical, formulation-related, and physiological. Generally, any factor that will influence the equilibrium solubility [Eq. 22.2)] of a therapeutic agent will likely influence the dissolution rate and then it may be reflected in the bioavailability. Examples of these factors include particle size, the salt form of a weak acid or base, polymorphism, and complexation.
Anatomical and Biological Imaging of Pediatric Brain Tumor
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
Rob A. Dineen, Shivaram Avula, Andrew C. Peet, Giovanni Morana, Monika Warmuth-Metz
DTI is an advanced MRI technique that is based on diffusion of water molecules as in DWI but also provides information on the direction of motion of the water molecule, enabling it to obtain microstructural parameters of the gray and white matter. The scan duration is longer than that of DWI as the diffusion gradient is applied in six or more directions. Whilst the image resolution can be improved using various methods, including increasing the number of gradient directions, these methods can prolong the scan time, increasing the chances of motion-related artefact. The parameters will therefore need to be optimized for children depending on the need (clinical versus research). Water molecules in normal white matter diffuse preferentially along the principal axis of axons in an anisotropic fashion (isotropic diffusion represents equal diffusion in all directions). Fractional anisotropy (FA) is a measurement derived from exploiting the anisotropic diffusion and reflects the alignment and integrity of the white-matter fibers. Measurement of diffusion can also be quantified as longitudinal or axial diffusivity (AD), which represents diffusivity along the principal axis, radial diffusivity (RA), the average diffusivity in the two minor axes, and mean diffusivity, which represents average diffusivity in all three axes.22,23
Basic Thermal Physics: Heat Exchange and Infrared Radiation
Published in Kurt Ammer, Francis Ring, The Thermal Human Body, 2019
The inverse of the ratio ρc/k is generally termed thermal diffusion or in other words thermal diffusivityα = k/ρcp (m2 · s−1) is the thermal conductivity of a substance divided by its density ρ and specific heat at constant pressure cp, [4]. Thermal diffusivity is a measure of how quickly a material can carry heat away from a hot source. Since material does not just transmit heat but must be warmed by it as well, α involves both the conductivity, k, and the volumetric heat capacity, ρc [12].
Altered connectivity of default mode and executive control networks among female patients with persistent post-concussion symptoms
Published in Brain Injury, 2023
Jimmy K. Y. Wong, Nathan W. Churchill, Simon J. Graham, Andrew J. Baker, Tom A. Schweizer
In addition to altered brain function, persistent symptoms are likely due to microscopic injury of white matter tracts, which form the neuroanatomical substrate for inter-regional communication (7). To assess such “structural connectivity” noninvasively, diffusion tensor imaging (DTI) may be used to assess changes in tissue microstructure, based on patterns of regional water diffusion predominantly in white matter fiber tracts. Metrics of interest include mean diffusivity (MD), characterizing the overall diffusion rate; and fractional anisotropy (FA), characterizing the tendency for water to diffuse in a preferred direction along the length of axons. Some studies also examine axial diffusivity (AD), which measures diffusion along the preferred direction, and radial diffusivity (RD), which measures diffusion perpendicular to the preferred direction. In previous studies of mTBI, patients have typically exhibited reduced FA and increased MD and RD, identified at an average of 1 week to 1 month post-injury (17–20). These DTI parameters may also provide insight into the mechanisms of injury and affected white matter tracts that give rise to altered brain function post-concussion.
Longitudinal Changes in the Sensorimotor Pathways of Very Preterm Infants During the First Year of Life With and Without Intervention: A Pilot Study
Published in Developmental Neurorehabilitation, 2021
Sonia Khurana, Megan E Evans, Claire E Kelly, Deanne K Thompson, Jennifer C. Burnsed, Amy D. Harper, Karen D. Hendricks-Muñoz, Mary S Shall, Richard D Stevenson, Ketaki Inamdar, Gregory Vorona, Stacey C Dusing
The emergence of new technology has allowed for advances in evaluation and diagnosis of brain injury. Structural MRI is a sensitive tool to identify subtle structural lesions and to provide further information regarding the volume and cortical morphology as compared to cranial ultrasound (cUS).1 Diffusion-weighted MRI (DWI) can evaluate the microstructural organization of the brain white matter, based on mapping of water diffusion in biological tissues.6 When combined with DWI analysis methods including Diffusion Tensor Imaging (DTI), parameters such as Fractional Anisotropy (FA), Mean Diffusivity (MD) and white matter volume can be extracted. These parameters provide an overall quantification of the underlying brain white matter structure, such as the axonal density and myelination.7 In addition, the availability of non-sedated MRI protocols has increased the safety of doing MRI in infants.
Differences in human IgG1 and IgG4 S228P monoclonal antibodies viscosity and self-interactions: Experimental assessment and computational predictions of domain interactions
Published in mAbs, 2021
Pin-Kuang Lai, Gaurav Ghag, Yao Yu, Veronica Juan, Laurence Fayadat-Dilman, Bernhardt L. Trout
The CG model was described elsewhere.27 Briefly, a 12-bead CG model derived from all-atom MD simulations was used to construct the structure of all the mAbs. The intramolecular interaction parameters were obtained from the dynamic averages of the MD simulations. The charges on the beads are the sum of all the atomic charges on the corresponding domains. The radii of the beads were calculated from the average radius of gyration from MD simulations. The CG models were treated as colloidal particles as applied in a previous work.48 Brownian dynamics simulation was used to describe the dynamic behaviors of the CG beads. The electrostatic interactions between the beads were approximated as a form of the Yukawa potential. The dispersion interactions were described as van der Waals interactions.27 The magnitude of interactions depends on the Hamaker constant, 27 The details are referred to the previous work.27 The calculation of self-diffusivity (D) follows a previous study.48 The single antibody diffusivity in free space (D0) was calculated by extrapolating the concentration-dependence of self-diffusivity to zero concentration.