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Particle Sciences - Technical Brief: 2012: Volume 9
Angstrom (Å) – a unit of length equal to one ten billionth of a meter or one tenth of a nanometer. Its symbol is the Swedish letter Å. Its most often used a measurement of atoms and molecules.
Micron (μ) – a metric system unit of length equal to one millionth of a meter. Its symbol is µ, the Greek letter mu. Most cells, hair, and drug particles are measured in microns.
Molecular mass – the sum of the mass of the atoms that make up a given molecule. The term molecular weight is often incorrectly used Interchangeably with molecular mass. The most common unit used is the kD (kilodalton). A kilodalton is 1000 Da (dalton). 1 Da equals the mass of 1 hydrogen atom.
Molecular weight – the average weight of a molecule, element, or compound measured in units once based on the weight of one hydrogen atom or alternatively, on 1/16 the weight of an oxygen atom, but after 1961, based on 1/12 the weight of a carbon atom.
Nanometer (nm) – a metric system unit of length equal to one billionth of a meter, abbreviated nm. 1000 nm = 1 μ = 0.001 millimeters. Viruses and drug nanoparticles are typically 10’s to 100’s of nm in diameter.
Surface area – the area of exposed surface of a given object. For nanoparticles, it is usually measured in meter2. Irregular or porous surfaces will have greater surface area compared to smooth objects of same overall dimensions. Higher surface area particulates will generally dissolve faster than lower surface area particles of the same material.
Molecular weight determination
Particle size analysis – the particle size distribution (PSD) of a powder, granular material, or particles dispersed in fluid, is a list of values or a mathematical function that defines the relative amount, typically by mass/volume, of particles present according to size. Knowledge of the PSD of a material is important in research, product development, processing, handling, packaging, and quality control. The PSD is needed to understand the physical and chemical properties of a suspension. The PSD is usually defined by the method by which it is determined.
Particle size reduction – commonly applied to a poorly soluble API in order to increase its bioavailability. The reduction in particle size results in a dramatic increase in surface area which in turn increases the material's dissolution rate, and thus increases "apparent" solubility. Particle size reduction may also be performed in order to increase homogeneity within a dosage form, especially for those forms with low API loading. Both wet and dry techniques exist, although the wet techniques are generally capable of resulting in smaller particle sizes.
Zeta potential determination Zeta potential (ZP) is a term used to describe the electrokinetic potential in colloidal systems. The ZP is the electric potential in the interfacial double layer at the location of the slipping (or shear) plane; it is the potential difference between the dispersion medium and the stationary layer of fluid attached to the dispersed particle. The significance of ZP is that its value is a surrogate for the surface charge (although the exact relation is complex and non-linear) and can be related to the stability of colloidal dispersions. The ZP indicates the degree of repulsion between similarly charged particles in a dispersion. ZP is not measurable directly but it can be calculated using theoretical models and an experimentally-determined electrophoretic mobility. Electrokinetic phenomena (electrophoresis, electro-osmosis, sedimentation potential, and streaming potential) and electroacoustic phenomena (colloid vibration potential and electrokinetic sonic amplitude) are the usual sources of data for calculation of ZP.
Block copolymer micelles (BCMs) – block copolymers like those used to prepare polymersomes can also form micelles in aqueous solution. The hydrophobic blocks of the individual polymer chains aggregate to form the core of the micelles, and the hydrophilic blocks extend from the core into the aqueous phase where they are solubilized and provide stabilization against further growth and aggregation. The core of BCMs can be loaded with hydrophobic drugs, and if made of biodegradable polymers, can release the drug over time by hydrolysis of the particle.
Cubosomes (see LyoCells®) – nanoparticles of bicontinuous cubic liquid crystalline phase. The aqueous domains form interpenetrating networks with the hydrophobic domains, and as such, LyoCells and cubosomes can encapsulate both hydrophobic and hydrophilic drugs and proteins.
Liposome – spherical nanoparticles made of one or more phospholipid bilayers surrounding an aqueous core. Liposomes are used to encapsulate water soluble APIs in the core, oil soluble APIs in the bilayer membrane, and if made of cationic phospholipids, trap and deliver oligonucleotides for gene therapy.
LyoCells® – reverse, cubic phase lipidic nanoparticles with hydrophobic and hydrophilic domains that are never more than a few nanometers apart giving the particles unique solubilization properties.
Micellar nanoparticles® – multiphasic compositions consisting of API distributed in micelles, nanoemulsion, crystalline (macro and nano), and continuous phase. These formulations are used for multiple routes of administration including transdermal delivery.
NanoCrystal Colloidal Dispersions® – crystalline, high melting, poorly water soluble API in the nanometer size range (<400 nm) that are stabilized in aqueous media. Stabilizers can be either non-ionic, ionic, or a combination of both.
Polymeric nanoparticle (PNP) – nanoparticles made of solid polymers, by top down or bottom up processes, such as solvent displacement. Typically a surfactant is used to stabilize the particles, but PEGylated polymers can be form self-stabilizing PNPs. Like SLNs, PNPs are useful for encapsulating hydrophobic drugs, or entrapping biologics on the surface. If the polymers are biodegradable polyesters, drugs can be released from the particle over time by degradation of the particle in vivo.
Polymersomes – similar to liposomes except that instead of using phospholipids to make the bilayers of the nanoparticle, synthetic block copolymers with a hydrophobic block and a hydrophilic block are used.
Quantum dots (Q-dots) – nanoparticles that are a few nm in diameter and made from semiconductor materials such as cadmium selenide. The electronic properties of Q-dots are determined by the particle size, and hence the optical properties of their dispersions (such as color) depend on particle size. Q-dots are used in diagnostics and imaging.
Solid lipid nanoparticle (SLN) – nanoparticles made of lipids that melt above room temperature, usually made by bottom-up methods such as melt-emulsify-cool or solvent displacement. Useful for encapsulating hydrophobic drugs that are soluble in the molten lipid and don’t recrystallize from it on cooling/hardening. Common lipids are carnauba wax, lecithin, cholesterol, bees wax, emulsifying wax, Compritol, and Dynasan. The nanoparticles are stabilized in aqueous dispersion by an adsorbed surfactant. If the surfactant is electrically charged, proteins, peptides, and oligonucleotides can be electrostatically attached to the surface for vaccination and gene therapy.
Agglomeration – is a process whereby aggregate particulate structures in a suspension stick together to create larger particulate complexes. Agglomerates are generally amenable to re-dispersion and are formed when aggregate suspensions settle or clump over time or are induced by the addition of chemical additives (coagulants and flocculants). Agglomerates are the larger size tail in any particle size distribution (PSD). The presence and structure of agglomerates directly affects suspension properties such as rheology.
Aggregation – is a process whereby individual (primary) particles in a suspension stick together to create particulate structures. Aggregates are formed when dispersions are dried; the forces involved are such that it is difficult and often impossible to reconstitute the original dispersion. Aggregates tend to be the major constituent fraction of any PSD.
Amorphous – an amorphous substance has no definite shape (or is irregularly shaped), or is formless and of no recognizable character. Importantly, an amorphous solid lacks the ordered structure of crystals; while there may be local ordering of the atoms or molecules in an amorphous solid, no long-term ordering is present.
Crystalline – a crystalline substance is a solid material whose constituent atoms, molecules, or ions are arranged in an ordered pattern extending in all three spatial dimensions. In addition to their microscopic structure, large crystalline solids are usually identifiable by their macroscopic geometrical shape, consisting of flat faces with specific, characteristic orientations.
Dispersant – a true dispersant (also known as a plasticizer) is a non-surface active substance added to a suspension, usually a colloid, to improve the separation of particles (usually by electrostatic forces), or to maintain the dispersed particles in suspension and prevent clumping over time.
Oligomer – is a molecule that consists of a relatively small and specifiable number of monomers (usually less than five). Unlike a polymer, if one of the monomers is removed from an oligomer, its chemical properties are altered.
Oswald ripening – is the phenomenon in which small particles (less than 1 µ) of very sparingly soluble materials dissolve and then subsequently recrystallize onto larger particles in order for the system to attain a more thermodynamically stable state – to lower its overall energy since smaller particles have a higher surface energy, hence a higher total Gibbs free energy. It does not occur for substances that are either completely soluble or are completely insoluble in a given medium. This shrinking and growing of particles will result in a larger mean diameter of a PSD over time. Ostwald ripening affects nucleation and precipitation processes and can lead to destabilization of dispersions and emulsions.
PEGylation – PEG is short for polyethylene glycol, a water soluble polyether that is often used as a dispersion stabilizer in food and drug products. PEGylation is the process of chemically conjugating PEG to a substance such as a hydrophobic drug molecule to increase its water solubility, or a protein molecule to reduce aggregation, or to a nanoparticle to make it “stealthy”, thereby avoiding clearance from the blood by macrophages and dendritic cells.
Polymer – any of the numerous natural and synthetic compounds of usually high MW consisting of up to millions of repeated, linked units, each a relatively light and simple molecule. A polymer can be a three-dimensional network (repeating units linked together left and right, front and back, up and down) or a two-dimensional network (repeating units linked together left, right, up, and down in a sheet) or a one-dimensional network (the repeating units linked left and right in a chain). Polymers can be crystalline or amorphous. A polymer of two or more different monomers is termed a copolymer and such materials have an array structure; a block copolymer consists of macromolecules in which comparatively long sequences of the links of one monomer (blocks) alternate with blocks of another monomer.
Surfactant – the term “surfactant” is a shortened form of "surface-active agent". A surfactant (also called a tenside) is a chemical that reduces the surface tension at the interface between water (or other fluid) and air or the interfacial tension between two fluids. Surfactants are compounds that are amphiphilic, meaning they contain both hydrophobic groups (their tails) and hydrophilic groups (their heads). They can be cationic, anionic or nonionic and they perform one or more functions including serving as detergents, wetting agents, foaming agents, emulsifiers, conditioning agents, and solubilizers.
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