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Biopharmaceutics > Parenteral drug administration > Flashcards

Parenteral drug administration Flashcards

1
Q

Why do diabetics typically inject in the abdomen?

A
  • 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
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2
Q

What are the characteristics of injectable medications?

A
  • fast action
  • complete/better absorption
  • predictable outcomes
  • drug targeting
  • short action
  • invasive administration
  • poor patient compliance
  • hospital visits
  • high cost
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3
Q

_____ order reactions have the same concentration over a constant period of time

A

zero

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4
Q

If we want to make the drug release more constant over a longer period of time, then we would want to increase the _____

A

solubility

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5
Q

What is the definition of a dispersed system?

A
  • 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
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6
Q

What is a lyophilic dispersion type?

A

a soluble dispersed phase in a continuous phase as in emulsions

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7
Q

What is a lyophobic dispersion type?

A
  • an insoluble dispersed phase in a continuous phase as in suspensions
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8
Q

What is an association dispersion type?

A
  • a soluble dispersed phase that is also self-assemble in a continuous phase as in liposomes
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9
Q

What is a depot formulation?

A
  • drug reservoirs
  • controlled drug release rate from the injection site
  • prolonged therapeutic effects
  • IM or SC administration
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10
Q

In a drug reservoir, the drug that is being eliminated is based on what?

A
  • on drug that is being absorbed
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11
Q

Will solubility be changed based on the environment of the drug?

A
  • no, it will not be. It is an inherent characteristic of the drug that will not change
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12
Q

Can the dissolution rate of a drug change?

A
  • yes- the dissolution rate can change. This is a rate property and can change based on how the drug is formulated
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13
Q

What are dissolution depots?

A
  • 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
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14
Q

What is the effect of increasing the particle size of drugs when they are injected?

A
  • it will act more like a depo and will stay in the blood for longer periods of time
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15
Q

What happens in roosters when you increase the size of testosterone particles?

A
  • 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
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16
Q

What are the properties associated with adsorption depots?

A
  • drug-absorbent binding
  • unbound absorption
  • continuous equilibrium
  • force of binding an ration of drug vs absorbent
  • aluminum hydroxide gels
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17
Q

What are the properties associated with esterification depots?

A
  • bioconvertible prodrugs (esters)
  • interfacial partition and prodrug bioconversion
  • relatively easy formulation and manufacture
  • actual commercial products
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18
Q

What are the properties of encapsulation depots?

A 
- microcapsules/microparticles/liposomes/
nanoparticles 
- polymers or macromolecules 
- barrier permeation or biodegredation 
- novel drug delivery systems 
- complex procedures
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19
Q

What are the properties of injectable emulsions?

A
  • aqueous and oil phases
  • emulsifiers
  • internal and external phases
  • w/o or o/w
  • drug can be in either phase
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20
Q

What is the advantage of o/w/o and w/o/w emulsions?

A
  • allow for stability of the drug in stable conditions

- very expensive however and will not be seen in practice much

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21
Q

Parenteral nutrition is most useful for what group of patients?

A
  • for terminally ill patients - provides them with amino acids, dextrose, electrolytes, minerals, vitamins, fatty acids
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22
Q

When there are two internal phases, the emulsion would be _____. What is this called?

A

more stable

- this is called a multiple emulsion

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23
Q

Describe a microemulsion?

A
  • small particles (under 1000 nm)
  • transparent
  • most parenteral emulsions belong to this category
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24
Q

What are some of the main side effects associated with emulsion type drugs?

A
  • emboli in lung/liver/kidney and brain

- headache/fever/chill/BP change/liver damage

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25
Q

What are the physiological requirements of emulsions?

A
  • stability
  • uniformity
  • sterility
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26
Q

What are the biological requirements of emulsions?

A
  • endotoxin free
  • non-antigenic
  • low side effects
  • metabolizable
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27
Q

What are the practical requirements of parenteral emulsions?

A
  • storage tolerance
  • easy processing
  • reasonable cost
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28
Q

Can emulsions be autoclaved?

A
  • 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
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29
Q

What is used as the main emulsifier in liquids?

A
  • lecithins (egg or soybean)
  • phosphatidylcholine is also used
  • glycerol or propylene glycol
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30
Q

What is the necessary pH for quality control of parenterals?

A
  • 6.6-6.8
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31
Q

What is the necessary particle size for particles?

A
  • 0.2 to 0.5 micrometers
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32
Q

IV liquid emulsions can be administered in combination with what?

A
  • dextrose and amino acids (drugs are generally not added, with the exception of heparin, insulin and ranitidine)
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33
Q

What are the components of injectable suspensions?

A
  • insoluble drug particles
  • aqueous or nonaqueous medium
  • suspending agents
  • most difficult formulation in terms of stability and production
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34
Q

Large particles are typically reserved for ___ infections

A

IM

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35
Q

Need to increased drug _______ due to insolubility in injectable suspensions

A

stability profiles

36
Q

What are the drug particle characteristics that are necessary for syringeability?

A
  • passing through needles
  • no clogging
  • dose accuracy
  • under 5 micrometers
  • 0.5-5% solids
37
Q

What are the drug particle characteristics that are necessary for inject ability?

A
  • good flow
  • even pressure
  • clogging free
  • less discomfort
  • viscosity related
  • excipient related
38
Q

What is used commonly as flocculating/suspending agents?

A
  • surfactants
  • polymers/colloids
  • electrolytes
39
Q

What is typically used as a wetting agent in an injection?

A
  • surfactants
40
Q

What are commonly used as stabilizers in injections?

A
  • antioxidants

- chelating agents (is used to bind metal ions)

41
Q

What are commonly used as adjustors in injections?

A
  • buffering agents

- tonicity agents

42
Q

What are the types of injections that require oils?

A
  • steroids, hormones and vitamins
43
Q

What is the chemical quality control that is done on injectables?

A

Testing needs to be done on:

  • active ingredients
  • degradation
  • preservatives
44
Q

What is the biological quality control that is done on injectables?

A
  • sterility test
  • pyrogen test
  • preservative action
45
Q

What is the physical quality control that is done on injectables?

A
  • resuspendibility
  • sedimentation
  • syringeability
  • crystal growth
  • size distribution
  • zeta potential
  • rheology
  • pH
  • dissolution
46
Q

What effect do pyrogens have?

A
  • induce fever

- can result in shock and death

47
Q

What are the characteristics of a pharmaceutical implant?

A
  • has long term action
  • steady drug concentrations
  • one administration
  • various release mechanisms
  • compliance
  • surgical procedures
  • complications
  • difficult retrieval
  • inflexibility
  • complex production
  • high unit cost
48
Q

What tissues are pharmaceutical implants intended for?

A
  • dermal/subdermal tissues
49
Q

What is a permeation controlled implant?

A
  • rate controlling polymer membrane

- permeation in/out of the system

50
Q

What is a diffusion controlled parenteral implant?

A
  • has a polymer matrix
  • insoluble polymers
  • diffusion in and out of the system
51
Q

Norplant 2 is both a ____ and ____ type controlled implant

A

permeation and diffusion

52
Q

What is a partition controlled implant?

A
  • dispersed drug micro reservoirs

- drug partition through the system

53
Q

What is a liposome delivery system?

A
  • a structure consisting of lipid bilayers separated by aqueous compartments (vesicles)
  • heterogeneous disperse systems
  • wide particle size distribution
  • phospholipids and cholesterol
54
Q

Some liposomes are approved to deliver ______

A

cancer drugs

55
Q

How do liposomes work to deliver drug to cancer cells?

A
  • 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
56
Q

Phospholipids are a major component of ____

A

liposomes

57
Q

What are the 2 most common types of phospholipids?

A
  • lecithin and cephalin
58
Q

What is considered to be the major stabilizer of liposomes?

A
  • cholesterol
59
Q

What is the purpose of cholesterol in liposomes?

A
  • decreasing bilayer fluidity/viscosity
  • reduces membrane permeability
  • minimizing interaction with biological fluids
60
Q

What are the other components that are typically found in liposomes?

A
  • polymers/surfactants/stabilizers
61
Q

Drugs with liposomes goes to the ____. This makes it valuable in treating what?

A
  • liver
  • makes it valuable in treating liver cancer- needs to be able to be taken up by the hepatocytes instead of the kumfer cells
62
Q

Hydrophilic drugs load into the ____ compartment

A

aqueous

63
Q

Lipophilic drugs load into the _____ compartment

A

lipophilic

64
Q

Amphipathic drugs load into the _________ compartment

A

depends!

- this depends on the partition coefficient

65
Q

Large molecules will sit at the ____ of the compound

A

surface

66
Q

Drug entrapment is dependent on the _______

A

internal volume of liquid

67
Q

Charged lipids increase the volume by _____

A

repulsion

68
Q

_____ solutions show higher entrapment

A

Diluted

69
Q

Drug _______ is common with liposomes

A

leachability

70
Q

What are some of the physical stability measures that we must be concerned about ensuring?

A
  • particle aggregation
  • particle fusion
  • phase change
  • drug leaching
71
Q

What is a stealth liposome?

A
  • polymer attachment
  • invisible in vivo
  • increased retention and stability
  • more site targeting
  • challenging formulation
72
Q

What is used as the final sterilization for parenterals?

A
  • microbial retentive filtration - should not affect the liposome structure
73
Q

What kinds of sterilization are thought to compromise the structural integrity and drug activity of liposomes?

A
  • thermal and radiation sterilization
74
Q

What size of filter is needed to be used to remove the majority of the bacteria in solution?

A

-0.22 micron filter

75
Q

What is the range of topics that nanotechnology covers?

A
  • colloidal sciences, supramolecular chemistry, device physics, engineering, etc
76
Q

What is the general size range of nanoparticles?

A
  • 10-1000 nm

- they are drug reservoir/matrix attachments with biodegradable polymers

77
Q

Emulsion evaporation has what procedure?

A
  • 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
78
Q

Salting out has what procedure?

A
  • 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
79
Q

Can you get 100% of the drug into the nanoparticles?

A
  • 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
80
Q

What is ultracentrifugation used for?

A
  • 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
81
Q

What are the 2 methods that can separate nanoparticles?

A
  • cross flow filtration

- ultracentrifugation

82
Q

What is the basis of dialysis?

A
  • 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
83
Q

What kind of polymer facilitates the fastest drug release? Hydrophilic of lipophilic?

A
  • hydrophilic
84
Q

What influences drug release rate and extent?

A
  • drug solubility, diffusivity, MW, and particle size
85
Q

What are the different components that need to be considered for an in vitro biological study?

A
  • interaction with blood components
  • uptake by cells
  • stability
  • toxicity
86
Q

What are the different components that need to be considered for an in vivo biological study?

A
  • animal models
  • drug targeting
  • drug activity
  • drug toxicity
  • overall outcomes

Biopharmaceutics (6 decks)

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