8 - Parenteral Flashcards
1
Q
Advantages of parenteral administration?
A
- fast action
- complete/better absorption
- predictable outcomes
- drug targeting
2
Q
Disadvantages of parenteral administration?
A
- short action
- invasive administration
- poor patient compliance
- hospital visits
- high cost
3
Q
What are “dispersed systems” ?
A
- a thermodynamic, interfacial system in which one component is dispersed in the other
- pharmaceutical colloids in nature
- stability, interfacial phenomena, mass transfer
- higher quality requirements that counterpart preparations for oral delivery
- complex and expensive formulation
4
Q
List 3 dispersion types
A
1) Lyophilic
2) Lyophobic
3) Association
5
Q
Dispersion type:
Describe Lyophilic
A
a soluble dispersed phase in a continuous phase as in emulsions
6
Q
Dispersion type:
Describe Lyophobic
A
an insoluble dispersed phase in a continuous phase as in suspensions
7
Q
Dispersion type:
Describe Association
A
a soluble dispersed phase that is also “self-assemble” in a continuous phase as in liposomes
8
Q
List different depot formulations
A
- suspensions (aqueous or oil)
- IM or SC administration
- drug reservoirs
- controlled drug release rate from injection site
- prolonged therapeutic effects
9
Q
What is the difference between dissolution and solubility?
A
Dissolution: how fast is that compound going to dissolve (relates to rate)
Solubility: does not relate to rate, just how much is going to dissolve in the solvent
10
Q
Describe 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
11
Q
The _____ the particle size, the more the depot (deposit?)
A
larger
12
Q
What are adsorption depots?
A
- drug-absorbent binding
- unbound absorption
- continuous equilibrium
- force of binding and ratio of drug vs. absorbent
- aluminum hydroxide gels
13
Q
Describe esterification depots
A
- bioconvertible prodrugs (esters)
- interfacial partition and prodrug bioconversion
- relatively easy formulation and manufacture
- actual commercial products
14
Q
Describe encapsulation depots
A
- microcapsules, microparticles, liposomes, nanoparticles
- polymers or macromolecules
- barrier permeation or biodegradation
- novel drug delivery systems
- complex procedures
15
Q
Describe injectable emulsions
A
- aqueous and oil phases
- emulsifiers
- internal and external phases
- W/O or O/W or W/O/W or O/W/O
- drug can be in either phase
16
Q
What kind of parenteral nutrition can be given for terminally ill patients?
A
amino acids, dextrose, electrolytes, minerals, vitamins, fatty acids
*can also have parenteral preparations for candidates with poor or no solubility in water
17
Q
Describe multiple emulsion
A
- hydrophilic & hydrophobic emulsifiers
- W/O/W or O/W/O
- two internal phases
- more stable
18
Q
Describe microemulsion
A
- small particles (< 1000 nm)
- transparent
- most parenteral emulsions belong to this category
19
Q
Most parenteral emulsions belong to which category?
A
microemulsion
20
Q
Describe some characteristics of emulsions
A
- Internal phase: stability, solubility
- Sustained release
- Drug targeting
- Particle size/stability
21
Q
List some side effects of emulsions
A
- Emboli in lung/liver/kidney/brain
- Headache/fever/chill/BP change/liver damage
22
Q
List some physicochemical requirements of emulsions
A
- stable
- uniform
- sterile
23
Q
List some biological requirements of emulsions
A
- endotoxin-free
- non-antigenic
- low side effects
- metabolizable
24
Q
List some practical requirements of emulsions
A
- storage tolerance
- easy processing
- reasonable cost
25
List an example of an emulsifier
- Lecithins
- Pluronic
- phosphatidylcholine
- glycerol/propylene glycol
- polysorbate
26
List examples of oil phases
- soybean oil
| - safflower oil
27
What is the aqueous phase?
water for injection
28
What other components of emulsifiers are controlled by other additives?
- pH
- osmolarity
- viscosity
- oxidation
- microbial growth
29
What does microfluidization do?
decreases particle size
30
What factors are considered in quality control?
1) pH = 6.6 - 6.8
2) Particle size = 0.2 - 0.5 micro meters
3) Surface charge (stability related, higher is preferable)
4) Stability
- Physical: particle change, creaming, coalescence, separation
- Chemical: Drug activity, hydrolysis, oxidation, pH change
- Microbiological: bacterial/fungal growth
31
Parabens are ______
preservatives
32
Describe administration of parenterals
- mostly IV injection (could be SC or IM I think)
- components of total nutrient admixture
- hospital applications
- storage in fridge for better stability
- incompatibility likely if admixing inappropriately
33
Hospital Dispensing:
| IV lipid emulsions can be administered in combo with _____ and ____ _____
dextrose and amino acids
34
Hospital Dispensing:
| ____ are generally not added to the admixtures, with rare exceptions (ex. heparin, insulin, ranitidine)
Drugs
35
Hospital Dispensing:
| What is the major concern?
physical stability
| ex. phase separation, precipitation
36
Describe Injectable Suspensions
- Insoluble drug particles
- Aqueous or non aqueous medium
- Suspending agents
- Most difficult formulation in terms of stability and production
37
Why are injectable suspensions the most difficult to formulate?
- drugs with limited aqueous solubility
- solubilization with pharmacological or toxicological compromise
- requirements for sustained drug release
- requirements for long-term local drug effects
38
Characteristics of injectable suspensions?
- Increase drug stability profiles due to insolubility
- Controlled release action
- Depot release
- Formulation stability issues
- Difficulty in formulation and production
- Discomfort to patients
- Dose accuracy
39
List some physicochemical requirements of injectable suspensions
- stable
- uniform
- sterile
40
List some biological requirements of injectable suspensions
- pyrogen-free
- non-irritating
- low side effects
41
List some practical requirements of injectable suspensions
- resuspendability
- syringeability
- injectability
- easy production
- easy administration
42
What is syringeability?
- passing through needles
- no clogging
- dose accuracy
- less than 5 micro meters
- 0.5-5% solids
43
What is injectability?
- good flow
- even pressure
- clogging-free
- less discomfort
- viscosity-related
- excipient-related
44
Injectable suspensions:
| What are some flocculating/suspending agents?
- surfactants
- polymers/colloids
- electrolytes
45
Injectable suspensions:
| What is a wetting agent?
surfactant
46
Injectable suspensions:
| Contain _______ to prevent microbial growth
preservatives
47
Injectable suspensions:
| What are some stabilizers
- antioxidants
| - chelating agents
48
Injectable suspensions:
| What are some adjustors?
- buffering agents
| - tonicity agents
49
Injectable suspensions:
| What are some solvents?
either water or oil
50
What are some requirements for oils for injection?
- pure
- biodegradable
- IM injection only as a vehicle
- IV injection as an emulsion
- mainly for steroids, hormones and vitamins
51
What are some types of oils for injection
- soybean oil
- safflower oil
- peanut oil
- cottonseed oil
- corn oil
- olive oil
- sesame oil
- apricot kernel oil
52
What is included in chemical quality control?
- active ingredients
- degradation
- preservatives
53
What is included in biological quality control?
- sterility test
- pyrogen test
- preservative action
54
What is included in physical quality control?
- resuspendibility
- sedimentation
- syringeability
- crystal growth
- size distribution
- zeta potential
- rheology
- pH
- dissolution
55
What are pyrogens?
Fever-inducing agents
| -Can cause a rise in temp of more than 0.6 degrees celsius
56
Pyrogens can result in ____ and _____
shock and death
57
What is an example of a pyrogen
bacterial LPS
58
Describe administration of injectable suspensions
- Mostly IM and SC injections
- slow/controleld release actions
- withdrawal from the ampoules
- discomfort to injection site
- not co-administered with other medications
59
Describe what pharmaceutical implants are
- devices in dermal/subdermal tissues for extended period of time
- sustained drug release profiles
- alternatives for long-term drug uses
- surfical implant and removal
60
Good characteristics of pharmaceutical implants?
- long-term actions
- steady drug concentrations
- one administration
- various release mechanisms
- compliance
61
Bad characteristics of pharmaceutical implants?
- surgical procedures
- complications
- difficult retrieval
- inflexibility
- complex production
- high unit cost
62
What is the objectives/purpose of pharmaceutical implants?
- delivering controlled drug release
- simplifying administration procedure
- minimizing medical implications
- reducing unauthorized misuse
- improving patient compliance
63
Pharmaceutical implants can either be permeation-controlled, diffusion-controlled or partition-controlled:
Describe premeation-controlled
- rate-controlling polymer membrane
| - permeation in/out of the system
64
Pharmaceutical implants can either be permeation-controlled, diffusion-controlled or partition-controlled:
Describe diffusion-controlled
- polymer matrix
- insoluble polymers
- diffusion in/out of the system
65
What is Norplant 2?
- membrane-matrix hybrid
| - both permeation and diffusion
66
Pharmaceutical implants can either be permeation-controlled, diffusion-controlled or partition-controlled:
Describe partition-controlled
- dispersed drug microreservoirs
| - drug partition through the system
67
What is an osmotic pump?
- osmotic-producing agnet
- universal formulation
- custom-made possible
68
Describe "Magnetic Activated"
- In vivo device
- In vitro control
- Both triggering and nontriggering
- Prototype
69
Describe the Application of magnetic activated
- decreasing use in humans
- research-based studies in animals
- long-term drug studies
- veterinary applications
70
Why are liposomes used in cosmetics?
Liposomes are lipid based and our skin has a high percentage of lipids so this will increase absorption
*If you apply lipids to other lipids (like dissolves like) and there will be a higher amount of drug delivery
71
What are liposomes?
- A structure consisting of lipid bilayers (to mimic our skin for best drug delivery) separated by aqueous compartments (vesicles)
- Heterogeneous disperse systems
- Wide particle size distribution
- Phospholipids and cholesterol
72
List the 3 types of liposome vesicles
- large unilaminar vesicle
- small unilaminar vesicle
- multi-laminar vesicle
73
What does sonication do?
breaks up particles
74
What does a vortex do?
causes high vibration rates and shakes the products to reduce particle size
75
What does reverse phase evaporation do?
solubilizes in an organic solvent, add water at higher temp allowing it to boil off
76
What does the french press method do?
uses high pressure to push particles through filter
77
Bonus question on exam!!!!
What was the car brand used in the asthma commercial?
Volvo
78
Bonus question on exam!!!!
Something about how tumours can be used to enhance drug delivery??
- tumor's vasculature is very good
| - has enhanced permeation and retention effect
79
______ = stabilizer of liposomes
Cholesterol
80
Using products with liposomes does scare some people about increasing their cholesterol. Is this a legitimate concern?
No - the amount of cholesterol used is very minimal
81
How does cholesterol stabilize liposomes?
- Decreases bilayer fluidity/viscosity
- Reducing membrane permeability
- Minimizes interaction with biological fluids
82
________ = naturally existing, abundant in vivo
Cholesterol
83
Cholesterol is also _______, ________, and ________
biocompatible, biodegradable and bioabsorbable
84
How are liposomes eliminated from the body?
- through the liver, but not in the traditional sense
- If it does get to liver or blood, immune cells with recognize liposomes and will start ingesting it
- macrophages of the liver with ingest liposomes and render them useless
* *they are going to the target tissue but not being effective because they are getting ingested
???? doesn't really make sense, but that's all I wrote down
85
What are some other components in liposomes?
-polymers, surfactants, stabilizers
86
What are liposomes used mainly in?
cosmetic and topical liposomes formulations
87
Caution use of liposomes in ??
parenteral formulations due to safety concerns
88
Where do hydrophilic drugs load?
aqueous compartments
89
Where do lipophilic drugs load?
within lipid bilayers
90
Where do amphipathic drugs load?
depending on PC
91
Where do large molecules load?
surfaces
92
Overall, drug loading in liposomes is relatively ____
low
93
Describe "Drug Entrapment"
- Entrapment dependent on internal volume
- Charged lipids increase volume by repulsion
- Diluted solutions show higher entrapment
- Drug leachability is common with liposomes
94
Liposomes:
| In vitro fate of particle size?
- physical stability
- uniformity
- drug loading
95
Liposomes:
| ______ particle size distribution is preferable
Narrower
96
Liposomes:
| In vivo fate of particle size?
- interaction with blood components
| - uptake by tissues and cells
97
Liposomes:
| _____ targeting possible by sorting particle size
Specific
98
What is the typical formula of a liposome?
- Egg lecithin 45%
- Phosphatidylserine 9.9%
- Cholesterol 45%
- Vitamin E 0.1%
99
Describe physical in vitro stability of liposomes
- dynamically instable
- particle aggregation
- particle fusion
- phase change (don't want fusion or phase change)
- drug leaching
*don't want aggregation or it to break apart
100
Describe chemical in vitro stability of liposomes
- hydrolysis
- oxidation
- pH
- membrane permeability
- drug delivery
-environmental related (light, air, temperature, etc)
101
Describe in vivo stability of liposomes
- various interactions in vivo
- instability due to protein transfer
- size and preparation related
- drug loss dramatic
- specific targeting possible but mechanisms not well studied and understood (leaky vasculature is a proposed theory)
- biggest challenge for medical application
102
Why do we create stealth liposomes?
Trying to allow liposomes to hide from the immune system therefore they would be allowed to reach the target tissue !!!
103
Describe Stealth Liposomes
- polymer attachment
- "invisible" to immune system in vivo
- increased retention and stability
- more site-targeting
- challenging formulation
* the longer the stage in blood, the more it can target cancer cells
* want to increase half life therefore allowing more particles to reach target site (cancer tumor)
104
We need to sterilize nanoparticles, what is the max size of nanoparticles for filtration?
0. 22 microns
| * Anything small can be filtered as a form of sterilization
105
Sterilization of liposomes:
| _____-_____ filtration for final sterilization
microbial-retentive
106
Sterilization of liposomes:
| _______ should not affect liposome structure
filtration
107
Sterilization of liposomes:
| _____ and ______ sterilization could compromise structure integrity and drug activity
thermal and radiation
108
Sterilization of liposomes:
| ______ manufacturing expensive and difficult in validation
Aseptic
109
Characteristics of liposomes?
- biocompatibility
- biodegradability
- small particles
- diverse drug loading
- parenteral use
- drug targeting
- instability
- high material cost
- large-scale production difficulties
110
What are the medical applications of liposomes?
- site-specific delivery
- site-avoidance delivery
- sustained/controlled drug release
- passive drug targeting to tumors
- protein/peptide/gene delivery
111
Describe nanotechnology
- Buzzword, promising potentials
- A broad range of topics: colloidal sciences, supramolecular chemistry, device physics, engineering, etc.
- Multidisciplinary and interdisciplinary
- More marketing strategies than actual applications
112
Pharmaceutical applications of nanotechnology?
- controlled release
- taste masking
- stability improvement
113
Food applications of nanotechnology?
- nutrient protections
- ingredient isolations
- odor/taste masking
114
Agriculture applications of nanotechnology?
- pesticides/fertilizers
- veterinary use
- chemical biodegradation
115
Commercial/industrial applications of nanotechnology?
- fragrance release
- detergent isolation
- thermal release
116
List some polymeric dispersions
- microcapsules
- microspheres
- nanocapsules
- nanospheres
- nanoparticles
117
Difficulties with nanoparticles?
- use of organic, toxic solvents
- operator protection
- environmental pollution/protection
- large-scale production
- production cost
118
Describe the separation of nanoparticles
- solvents
- free drugs
- polymers
- additives
119
Describe the purification of nanoparticles
- stability
- toxicity
- quality
- injectability
120
What is ultracentrifugation?
- spin it at high rates and separate particles
| - once nanoparticles settle to the bottom, we can separation the organic solvent from it
121
How can the principle of dialysis be related to separation of nanoparticles
Put nanoparticles in the bag and spin it in the beaker.
Buffer = water in this case
(water is considered low salt/low solute)
Organic solvents want to come out of the bag (follow concentration gradient).
Dialysis bag is semi-permeable membrane and nanoparticles that are too big to leave the bag while everything else smaller than that is able to leave the bag
*just using a barrier (dialysis bag) to separate particles based on size
122
What is included in physical quality control?
- Size & distribution (dynamic light scattering)
- Morphology (SEM)
- Drug loading
- Drug release
- Physical states
123
What is included in chemical quality control?
- Drug activity (functional assays)
- Degradation (HPLC)
- Byproducts
- Additives (HPLC)
- Interactions
124
How can the drug be released from nanoparticles?
- Hydrophilic polymers facilitate faster drug release than lipophilic polymers
- Drug solubility, diffusivity, molecular weight and particle size influence drug release rate and extent
- Controlle released is achievable by formulation strategies
Drug can release by:
1) nanoparticles eroding
2) drug diffuses out of nanoparticles
3) temp changes could increase or decrease drug release
125
In vitro = ?
outside of body (test tube)
126
In vivo = ?
in the body
127
Describe in vitro studies
- interaction with blood components
- uptake by cells
- stability
- toxicity
128
Describe in vivo studies
- animal models
- drug targeting
- drug activity
- drug toxicity
- overall outcomes
129
Liposomes are ___ based
lipid
130
Nanoparticles are _____ based
polymer
