PubMed · 14260237
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I S FRIEDMAN, J SCHERRER. 1965-03-15. A DISPOSABLE MICROHYDROMETER.. https://doi.org/10.1001/jama.1965.03080110065024
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Recently, colloidal dispersions made from mixtures of solid and liquid lipids were described to combine controlled release characteristics with higher drug loading capacities than solid lipid nanoparticles (SLN). It has been proposed that these nanostructured lipid carriers (NLC) are composed of oily droplets which solubilize the drug and which are embedded in a solid lipid matrix. The structures of SLN and NLC based on glyceryl behenate and medium chain triglycerides were characterized by photon correlation spectroscopy (PCS) and laser diffraction (LD), field-flow fractionation (FFF) with multi-angle light scattering detection (MALS), and cryo transmission electron microscopy (cryo TEM). PCS indicates that SLN and NLC differ from a nanoemulsion with respect to Brownian motion due to asymmetric particle shapes. Non-spherical particles, in case of SLN and NLC, lead to higher polydispersity indices compared to the nanoemulsion. In FFF, the nanodroplets elute much earlier than SLN- and NLC-platelets although their PCS and LD data show similar particle sizes. In TEM platelet (for SLN), oil loaded platelet ("nanospoons"; for NLC) and droplet (for nanoemulsion) structures were observed. In contrast to literature reports, the investigated SLN appear as thin platelets. NLC are found to be lipid platelets with oil spots sticking on the surface. Very short diffusion pathways in platelets, increased water-lipid interfaces and low drug incorporation in crystalline lipids are the drawback of SLN and NLC compared to conventional nanoemulsions.
Solid state properties including polymorphism, solvate and salt formation can have a profound impact on two of the most important properties that are essential to the successful development of drug candidates: solubility and stability. To enable meaningful evaluations of drug candidates for their development risks, often referred to as developability, and provide input to the molecular design regarding the "drug-like" properties, one must take into account the impact of solid state properties on solubility and stability. This review examines the importance of solid state properties and their relationship to developability criteria. Phase appropriate characterization strategies and appropriate salt and crystal form screening and selection processes are discussed. These strategies and processes should balance the need for speed and throughput of modern discovery with the quality of data essential to the adequate developability assessment. Specific examples are given to illustrate the importance of understanding the solid state properties and their impact on developability.
Stimulated emission pumping (SEP)-hole filling spectroscopy and SEP-induced population transfer spectroscopy have been used to place narrow bounds on the energy thresholds for isomerization between individual reactant-product isomer pairs involving the seven conformational minima of tryptamine. The thresholds for isomerizing conformer A to all six other conformations divided into three groups at 750 wavenumbers (cm-1)(A-->B, F), 1000 cm-1 [A-->C(2)], and 1280 to 1320 cm-1 [A-->D, E, and C(1)]. The appearance of the first band and the absence of the band below it were used to place upper and lower bounds to the barrier heights for each process. The thresholds for A-->B and B-->A isomerizations were also combined to determine the relative energies of these two lowest energy minima. The combined data from all X-->Y isomerizations identify important isomerization pathways on the potential energy surface linking the minima.