microparticles Flashcards
advantages of microencapsulation/aims of long acting drug delivery
reduces dosing frequency, reduces fluctuations in drug plasma levels, drug plasma conc maintained in therapeutic range for extended period of time
why is it better to have bigger particles (max size for injections)
easier to control release
requirements for materials in long acting injectable formulations
biodegradable, degrades chemically/enzymatically in vivo to inert/non toxic products/normal metabolites, non immunogenic, non teratogenic, non carcinogenic
name 3 production methods of long acting injectable formulations
chemical- polymerisation, nanoparticles
physical- fluidisation, supercritical fluid methods
physiochemical- phase separation, emulsification solvent evaporation
advantages and disadvantages of emulsification based methods
advantages= versatile, can be modified, incorporation of hydrophobic drugs (O/W) and incorporation of proteins/DNA (W/O/W, surface loading)
disadvantages= particles must be small, several stages in production process, toxicity of organic solvents, surfactant can solubilise drug and reduce encapsulation efficiency and loading
describe green preparation method
polymer dissolved in a supercritical fluid, this high pressure solution is rapidly depressurised through an orifice to lead to polymer precipitation at low pressure, process based on solubility difference of polymer in supercritical fluids and high and low pressures, no use of chlorinated organic solvent
name 3 drug release mechanisms
fick’s law, higuchi model, matrix erosion and diffusion
factors that influence drug release
-particle, size/morphology/density of matrix/membrane/presence of pores
-drug, nature/solubility/pK/MW/physical state inside a particle/drug diffusivity in polymeric material and in outside medium
-polymeric material, crystallinity/porosity/tortuosity/degradation properties/swelling
-milieu/environment, pH/enzymes/temperature
name 2 nanoparticle production technologies (?)
- phase separation based method for polymeric and macromolecular- mix solvated with non solvent to make desolvated
- phase separation based methods for lipid type materials- lipid dissolved in organic solvent miscible with water (alcohol), nucleic acid (eg. siRNA, mRNA) dissolved in water (water based buffer)’-phase separation of lipid materials when alcohol and water mix entraps NA molecules
what is unilamellar and multilamellar liposomes
unilamellar liposomes=have single phospholipid bilayer sphere enclosing aqueous solution (buffer)
multilamellar liposomes=onion structure, several unilamellar vesicles form inside each other diminishing in size, creating layers separated by layers of water
describe drug incorporation into unilamellar and multilamellar liposomes
-inside aq centre of unilamellar liposome or aq spaces between layers in multilamellar=incorporation of water soluble (hydrophilic) drug
-within hydrocarbon interiors of lipid bilayer=incorporation of lipid soluble drug (lipophilic)
describe the preparation of liposomes
-formed when thin lipid films are hydrated and stacks of liquid crystalline bilayers become fluid and swell
-hydrated lipid sheets detach during agitation and self close to form large multilamellar vesicles which prevent interaction of water with hydrocarbon core of bilayer at the edges
-reducing size of these particles ^ require energy input in form of sonic energy (sonication) or mechanical energy (extrusion)
describe the drug release from a large multilamellar liposome injected locally
remains at site of injection, release drug as they gradually disintegrate
describe the drug release from a small liposome in blood following intravenous administration
becomes leaky and lose incorporated drug (may lose before reaching target tissue), attributed to plasma high density lipoproteins removing phospholipids molecules from liposomal bilayer
what can be changed to increase drug retention time
change liposomal composition
