Parenteral drug administration Flashcards
Why do diabetics typically inject in the abdomen?
- allows for SC infection that has the fastest absorption due to the lower fat levels
- the thighs would then be the next site of injection
- if you injected in the thighs and then exercised right after- then the rate of absorption would increase from the thighs
What are the characteristics of injectable medications?
- fast action
- complete/better absorption
- predictable outcomes
- drug targeting
- short action
- invasive administration
- poor patient compliance
- hospital visits
- high cost
_____ order reactions have the same concentration over a constant period of time
zero
If we want to make the drug release more constant over a longer period of time, then we would want to increase the _____
solubility
What is the definition of a dispersed system?
- a thermodynamic, interfacial system in which one component is dispersed in the other
- in nature they are called pharmaceutical colloids
- stability, interfacial phenomena, mass transfer
What is a lyophilic dispersion type?
a soluble dispersed phase in a continuous phase as in emulsions
What is a lyophobic dispersion type?
- an insoluble dispersed phase in a continuous phase as in suspensions
What is an association dispersion type?
- a soluble dispersed phase that is also self-assemble in a continuous phase as in liposomes
What is a depot formulation?
- drug reservoirs
- controlled drug release rate from the injection site
- prolonged therapeutic effects
- IM or SC administration
In a drug reservoir, the drug that is being eliminated is based on what?
- on drug that is being absorbed
Will solubility be changed based on the environment of the drug?
- no, it will not be. It is an inherent characteristic of the drug that will not change
Can the dissolution rate of a drug change?
- yes- the dissolution rate can change. This is a rate property and can change based on how the drug is formulated
What are dissolution depots?
- salts and complexes with low solubility
- suspensions of microcrystals
- slow drug dissolution from formulation or into biological fluid
- dissolution could be alone or in combination with vehicle
What is the effect of increasing the particle size of drugs when they are injected?
- it will act more like a depo and will stay in the blood for longer periods of time
What happens in roosters when you increase the size of testosterone particles?
- you will see the comb growth over longer periods of time in the castrated roosters that you would in a smaller particle size of testosterone
What are the properties associated with adsorption depots?
- drug-absorbent binding
- unbound absorption
- continuous equilibrium
- force of binding an ration of drug vs absorbent
- aluminum hydroxide gels
What are the properties associated with esterification depots?
- bioconvertible prodrugs (esters)
- interfacial partition and prodrug bioconversion
- relatively easy formulation and manufacture
- actual commercial products
What are the properties of encapsulation depots?
- microcapsules/microparticles/liposomes/ nanoparticles - polymers or macromolecules - barrier permeation or biodegredation - novel drug delivery systems - complex procedures
What are the properties of injectable emulsions?
- aqueous and oil phases
- emulsifiers
- internal and external phases
- w/o or o/w
- drug can be in either phase
What is the advantage of o/w/o and w/o/w emulsions?
- allow for stability of the drug in stable conditions
- very expensive however and will not be seen in practice much
Parenteral nutrition is most useful for what group of patients?
- for terminally ill patients - provides them with amino acids, dextrose, electrolytes, minerals, vitamins, fatty acids
When there are two internal phases, the emulsion would be _____. What is this called?
more stable
- this is called a multiple emulsion
Describe a microemulsion?
- small particles (under 1000 nm)
- transparent
- most parenteral emulsions belong to this category
What are some of the main side effects associated with emulsion type drugs?
- emboli in lung/liver/kidney and brain
- headache/fever/chill/BP change/liver damage
What are the physiological requirements of emulsions?
- stability
- uniformity
- sterility
What are the biological requirements of emulsions?
- endotoxin free
- non-antigenic
- low side effects
- metabolizable
What are the practical requirements of parenteral emulsions?
- storage tolerance
- easy processing
- reasonable cost
Can emulsions be autoclaved?
- there are some emulsions that can be autoclaved- as long as the active ingredient is stable enough to be autoclaved then a small breakdown in oil is manageable
What is used as the main emulsifier in liquids?
- lecithins (egg or soybean)
- phosphatidylcholine is also used
- glycerol or propylene glycol
What is the necessary pH for quality control of parenterals?
- 6.6-6.8
What is the necessary particle size for particles?
- 0.2 to 0.5 micrometers
IV liquid emulsions can be administered in combination with what?
- dextrose and amino acids (drugs are generally not added, with the exception of heparin, insulin and ranitidine)
What are the components of injectable suspensions?
- insoluble drug particles
- aqueous or nonaqueous medium
- suspending agents
- most difficult formulation in terms of stability and production
Large particles are typically reserved for ___ infections
IM
Need to increased drug _______ due to insolubility in injectable suspensions
stability profiles
What are the drug particle characteristics that are necessary for syringeability?
- passing through needles
- no clogging
- dose accuracy
- under 5 micrometers
- 0.5-5% solids
What are the drug particle characteristics that are necessary for inject ability?
- good flow
- even pressure
- clogging free
- less discomfort
- viscosity related
- excipient related
What is used commonly as flocculating/suspending agents?
- surfactants
- polymers/colloids
- electrolytes
What is typically used as a wetting agent in an injection?
- surfactants
What are commonly used as stabilizers in injections?
- antioxidants
- chelating agents (is used to bind metal ions)
What are commonly used as adjustors in injections?
- buffering agents
- tonicity agents
What are the types of injections that require oils?
- steroids, hormones and vitamins
What is the chemical quality control that is done on injectables?
Testing needs to be done on:
- active ingredients
- degradation
- preservatives
What is the biological quality control that is done on injectables?
- sterility test
- pyrogen test
- preservative action
What is the physical quality control that is done on injectables?
- resuspendibility
- sedimentation
- syringeability
- crystal growth
- size distribution
- zeta potential
- rheology
- pH
- dissolution
What effect do pyrogens have?
- induce fever
- can result in shock and death
What are the characteristics of a pharmaceutical implant?
- has long term action
- steady drug concentrations
- one administration
- various release mechanisms
- compliance
- surgical procedures
- complications
- difficult retrieval
- inflexibility
- complex production
- high unit cost
What tissues are pharmaceutical implants intended for?
- dermal/subdermal tissues
What is a permeation controlled implant?
- rate controlling polymer membrane
- permeation in/out of the system
What is a diffusion controlled parenteral implant?
- has a polymer matrix
- insoluble polymers
- diffusion in and out of the system
Norplant 2 is both a ____ and ____ type controlled implant
permeation and diffusion
What is a partition controlled implant?
- dispersed drug micro reservoirs
- drug partition through the system
What is a liposome delivery system?
- a structure consisting of lipid bilayers separated by aqueous compartments (vesicles)
- heterogeneous disperse systems
- wide particle size distribution
- phospholipids and cholesterol
Some liposomes are approved to deliver ______
cancer drugs
How do liposomes work to deliver drug to cancer cells?
- they have enhanced permeation and retention effects
- works by in cancer the tumours need nutrients to continue to grow
- they undergo androgenesis to create vasculature- the vasculature is leaky
- the liposomes take advantage of the leaky vasculature at the tumour site- this is why it is called enhanced permeation
- it is using the side effects of tumours to enhance drug delivery- because of the leaky vasculature we are going to get accumulation
Phospholipids are a major component of ____
liposomes
What are the 2 most common types of phospholipids?
- lecithin and cephalin
What is considered to be the major stabilizer of liposomes?
- cholesterol
What is the purpose of cholesterol in liposomes?
- decreasing bilayer fluidity/viscosity
- reduces membrane permeability
- minimizing interaction with biological fluids
What are the other components that are typically found in liposomes?
- polymers/surfactants/stabilizers
Drugs with liposomes goes to the ____. This makes it valuable in treating what?
- liver
- makes it valuable in treating liver cancer- needs to be able to be taken up by the hepatocytes instead of the kumfer cells
Hydrophilic drugs load into the ____ compartment
aqueous
Lipophilic drugs load into the _____ compartment
lipophilic
Amphipathic drugs load into the _________ compartment
depends!
- this depends on the partition coefficient
Large molecules will sit at the ____ of the compound
surface
Drug entrapment is dependent on the _______
internal volume of liquid
Charged lipids increase the volume by _____
repulsion
_____ solutions show higher entrapment
Diluted
Drug _______ is common with liposomes
leachability
What are some of the physical stability measures that we must be concerned about ensuring?
- particle aggregation
- particle fusion
- phase change
- drug leaching
What is a stealth liposome?
- polymer attachment
- invisible in vivo
- increased retention and stability
- more site targeting
- challenging formulation
What is used as the final sterilization for parenterals?
- microbial retentive filtration - should not affect the liposome structure
What kinds of sterilization are thought to compromise the structural integrity and drug activity of liposomes?
- thermal and radiation sterilization
What size of filter is needed to be used to remove the majority of the bacteria in solution?
-0.22 micron filter
What is the range of topics that nanotechnology covers?
- colloidal sciences, supramolecular chemistry, device physics, engineering, etc
What is the general size range of nanoparticles?
- 10-1000 nm
- they are drug reservoir/matrix attachments with biodegradable polymers
Emulsion evaporation has what procedure?
- chlorinated solvent is used as a polymer with surfactant water, mixed together to create a o/w emulsion, and then the solvent is evaporated to create a mixture of raw nanospheres
Salting out has what procedure?
- acetone is used as a polymer and then added to a salting out agent such as polyvinyl alcohol or water
- creates an o/w emulsion
- water is then added to this, to create a mixture of raw nanospheres
Can you get 100% of the drug into the nanoparticles?
- no! you never will, you have to get rid of the free drug in solution
- the free drug can be eliminated from the body without having any reaction
What is ultracentrifugation used for?
- separates different particles - spins very fast to separate the drug particles
- separates materials based on the density
- we hope that the nanoparticles are heavies that the rest of the particles so that they separate in the solution
- instead of separating her, the filter can eventually clog
- hoping that the organic solvents can fall through
What are the 2 methods that can separate nanoparticles?
- cross flow filtration
- ultracentrifugation
What is the basis of dialysis?
- dialysis is the same process of centrifugation- spinning of the blood to separate the toxins
- dialysis is something that can be used to separate out compounds as well
What kind of polymer facilitates the fastest drug release? Hydrophilic of lipophilic?
- hydrophilic
What influences drug release rate and extent?
- drug solubility, diffusivity, MW, and particle size
What are the different components that need to be considered for an in vitro biological study?
- interaction with blood components
- uptake by cells
- stability
- toxicity
What are the different components that need to be considered for an in vivo biological study?
- animal models
- drug targeting
- drug activity
- drug toxicity
- overall outcomes
