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Ceutics final > Parenteral drug delivery > Flashcards

Parenteral drug delivery Flashcards

1
Q

define parenteral drug delivery

A

administration of drugs that bypasses the GI tract

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2
Q

How can you achieve rapid drug delivery for IM and SC delivery?

A

If the drugs are administered in aqueous solution, drug delivery can be quite rapid

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3
Q

rapid drug absorption by parenteral admin is normally followed by what?

A

Followed by a rapid decline in drug levels in the systemic circulation

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4
Q

Describe continuous IV infusion

A

A constant and sustained drug level within therapeutic concentration range is maintained

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5
Q

Significance of Charles Pravez and Alexander Wood

A

Invented the modern hypodermic needle in 1853

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6
Q

Describe SC injections

A

done directly into a fatty skin area. Slower absorption

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7
Q

Injection advantages

A
  • fast onset
  • complete/better absorption
  • predictable outcomes
  • drug targeting
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8
Q

Injection disadvantages

A
  • short duration of action
  • invasive administration
  • poor patient compliance
  • hospital visits
  • high cost
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9
Q

Describe one of the most successful parenteral formulations

A

The depot preparation

  • can be either an aqueous (or oleaginous) suspension or an oleaginous (lipid soluble) solution
  • depot acts as a drug reservoir that releases the drug molecules continuously at a rate determined by the characteristics of the formulation
  • leads to prolonged drug absorption from the formulation
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10
Q

Advantage of controlled-release depot injections

A
  • reduced drug dose
  • decreased SE’s
  • enhanced patient compliance
  • improved therapeutic outcomes
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11
Q

Disadvantage of depot injections

A

Same as injections in general, which is invasiveness and painfulness

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12
Q

Depot injections should be administered by a HCP to obtain optimal therapy and safety: T/F

A

True.

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13
Q

Give 4 examples of depot products

A

1) depo-Medrol: a glucocorticoid sterile aqueous suspension for IM admin
2) Depo-Provera: progestogen for contraceptive control. Is a sterile aqueous suspension.
3) Modecate: an antipsychotic oleaginous solution injection
4) Norplant: contraceptive implant requiring subdermal incision

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14
Q

List the 4 categories commonly used approaches in the devl of parenteral CR/SR formulations. Briefly describe each

A

1) Physical: viscosity, co-solvents, adsorption
2) chemical: insoluble salts/esters, prodrugs
3) biological: vasoconstrictors
4) Formulation: emulsions, suspensions, liposomes, microparticles

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15
Q

Describe 7 commonly used techniques in the devl of parenteral CR/SR formulations

A

1) Use of viscous, water-miscible vehicles, such as an aqueous sol’n of gelatin and PVP
2) Use of water-insoluble vehicles (eg: veg oils) plus a water-repelling agent (Al monostearate)
3) Formation of thixotropic suspensions
4) Use of water-insoluble drug derivatives, such as salts, complexes, and esters
5) Formation of polymeric microspheres or microcapsules, such as lactide-glycolide copolymers
6) Formation of liposomes
7) Co-admin. of vasoconstrictors

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16
Q

List 3 modes of parenteral drug delivery

A
  • IV (intravenous)
  • IM (intramuscular)
  • SC (subcutaneous)
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17
Q

List the 4 different drug release mechanisms seen with depot parenteral formulations

A

1) dissolution-controlled depot
2) adsorption-type depot
3) encapsulation-type depot
4) esterification-type depot

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18
Q

Drug release mechanism (MODR) of a dissolution-controlled depot

A

Drug absorption rate is controlled by the slow dissolution of drug particles in the formulation or in the tissue fluid surrounding the formulation. Selection of salts or complexes with low aqueous solubility or formulation of macrocrystal suspensions will produce desired characteristics

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19
Q

Major drawback of dissolution-controlled depot

A

Drug release is not zero-order, as is normally expected from theoretical calculations.

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20
Q

What 2 reasons might explain why dissolution-controlled depots may not release drugs in zero-order rates?

A

1) the surface area of the drug particles diminishes with time because of increased drug dissolution
2) the saturation solubility of the drug at injection site can’t be easily maintained because of rapid absorption

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21
Q

Using the example of testosterone depot admin, describe the effect of particle size on rooster comb growth

A
  • the smaller particle sizes were absorbed faster and thus had a faster onset, but had a shorter DOA. They also were associated with reaching higher therapeutic plasma drug concentrations.
  • larger particle sizes took longer to be absorbed, but had a longer DOA
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22
Q

Briefly summarize dissolution depots

A
  • salts and complexes with low solubility
  • suspensions of microcrystals
  • slow drug dissolution from formulation nor into biological fluid
  • dissolution could be alone or in combination with a vehicle
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23
Q

Describe the MODR of adsorption-type depots

A

The depot preparation is formed by binding drug molecules to adsorbends such as AlOH gel. Only unbound free drug is available for absorption. As soon as the unbound drug molecules are absorbed, a fraction of the bound drug is released to MAINTAIN EQUILIBRIUM

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24
Q

Why might some vaccines be given as an adsorption-type depot?

A

Use this mechanism to sustain drug release and hence prolong the duration of stimulation of antibody formation

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25
Q

MODR for encapsulation-type depots

A

This depot preparation is made by encapsulating drug solids within a permeation barrier or dispersing drug particles in a diffusion matrix. These materials are biodegradable or bioabsorbable macromolecules. The release rate is controlled by permeation rate of the barriers or by the biodegradation rate of the macromolecules [aka release is controlled by barrier permeation or biodegradation]

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26
Q

Encapsulation depots consist of what

A

microcapsules, microparticles, liposomes, nanoparticles

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27
Q

List materials that encapsulation depot barriers might be made of

A

Biodegradable or bioabsorbable macromolecules such as gelatin, dextran, polylactate, phospholipids.

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28
Q

MODR of esterification-type depots

A

This formulation is produced by esterifying the drug to form a bioconvertible prodrug ester and then preparing it as an injectable. The drug absorption rate is controlled by the interfacial partitioning of drug esters from the reservoir to the tissue fluid, and the bioconversion of inactive drug esters to active drug molecules.

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29
Q

Why are emulsions being increasingly used over aqueous/oleaginous solutions for parenteral injections?

A

Because of their ability to incorporate drugs within the internal phase, resulting in better solubility and stability. Emulsions may also be used for site-specific delivery.

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30
Q

How can injectable emulsions be controlled or sustained release?

A

Since the drug is not in direct contact with the body fluid, the partitioning of the drug from the internal to the external phase may contribute to a sustained drug release profile

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31
Q

A more prolonged drug delivery can be achieved through the use of multiple emulsions (W/O/W, O/W/O): T/F

A

True

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32
Q

most commonly used oil in emulsions

A

natural veggie sources of long chain triglycerides (LCTs) like soybean oil and safflower oil

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33
Q

How can you purify veg oils to be used for injection?

A

treatment with silicic acid or silica gel to remove undesirable components such as peroxides, pigments, thermal and oxidative decomposition products.

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34
Q

Natural oils have to be checked for what

A

presence of aflatoxins, herbicides, and pesticides

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35
Q

Emulsifiers are common agents added to injectable emulsions: T/F

A

false. Parenteral toxicity has eliminated many emulsifying agents that might be used in emulsions. Can lead to hemolytic reactions

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36
Q

What is the most frequently used emulsifier used in injectable emulsions (when appropriate). What makes it a good choice?

A

Natural lecithin. It is metabolized in the same way as fat and is not excreted via the kidneys

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37
Q

Most phosphatide emulsions are very unstable: T/F

A

False. Some are very stable; resisting hydrolysis and oxidation if processed under inert atmosphere

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38
Q

Why are additives to the aqueous phase required in parenteral emulsions?

A

emulsified oil exerts no osmotic effect, and we want to produce isotonic conditions in parenterals

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39
Q

What parameters do we want to adjust or control in emulsions?

A
  • osmolarity
  • pH
  • oxidation
  • microbial growth
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40
Q

T/F: most parenteral emulsions are multiple emulsions (ex: have W/O/W) because they’re more stable

A

False. Most are microemulsions

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41
Q

Why should you not add NaCl, Glc, and dextrose to the aqueous phase of emulsions

A

they interact with the emulsifier

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42
Q

What is a good additive to the aqueous phase to produce isotonic conditions in parenterals?

A

glycerol

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43
Q

Most stable pH range of emulsions

A

6.6-6.8

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44
Q

Why might you add an antioxidant to an injectable emulsion?

A

to prevent peroxidation of unsaturated fatty acids

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45
Q

Optimal stability of emulsions is largely dependent on what?

A

pH

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46
Q

Why do we adjust the pH of emulsions to be 8 prior to sterilization?

A

Optimal pH is from 6.6-6.8, but the pH or the formulation falls upon autoclaving and during storage when the hydrolysis of glyceride and phosphatide produces FFA’s. We are adjusting for it.

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47
Q

What do we use to adjust emulsion pH to 8?

A

sodium hydroxide

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48
Q

Why is pH so important in emulsions?

A

need to maintain desired particle size. pH affects the surface charge of particles, and a low pH (<5) can reduce electrostatic repulsion btw emulsified oil particles, resulting in particle aggregation.

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49
Q

Side effects of injectable emulsions

A
  • Emboli in lung/liver/kidney/brain
  • headache
  • fever/chillls
  • BP change
  • liver damage
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50
Q

Particle sizer greater than 10um increase the incidence of emboli and BP changes in injectable emulsions: T/F

A

F. Particle sizes greater than 4-6um cause those AE’s.

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51
Q

T/F: smaller particle size (200-500nm) for fat emulsions leads to formulations with highest physical stability

A

True

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52
Q

T/F: increasing oil concentration in an emulsion by >10% can significantly increase the particle size

A

True

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53
Q

What are physicochemical requirements for injectable emulsions?

A
  • stability
  • uniformity
  • sterility
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54
Q

What are biological requirements for injectable emulsions?

A
  • endotoxin-free
  • non-antigenic
  • low side effects
  • metabolizable
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55
Q

What are practical requirements for injectable emulsions?

A
  • storage tolerance
  • easy processing
  • reasonable cost
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56
Q

Components of emulsions: List the different possibilities for each ingredient: Oil phase, aqueous phase, emulsifiers, Additives

A
  • Oil phase: soybean oil, safflower oil
  • Aqueous phase: water
  • Emulsifiers: lecithins
  • Other additives: for pH, osmolarity (glycerol), oxidation (antioxidants like ascorbic acid), prevention of microbial growth
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57
Q

What role does surface charge play in the stability of emulsions

A

Ionized lipids have a favorable effect on emulsion particle size and stability through an increse in the surface charge and bilayer thickness of phospholipid films. A reduction in electrical charge can lead to flocculation.

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58
Q

Define flocculation

A

Fine particles are caused to clump together, forming a floc

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59
Q

Stability of emulsions can be influenced by what?

A
  • processing conditions
  • autoclaving
  • storage conditions
  • excessive shaking
  • addition of electrolytes or drugs
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60
Q

Physical instability of an emulsion is indicated by what

A
  • particle size changes
  • flocculation
  • creaming
  • coalescence
  • oil separation
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61
Q

Chemical instability of an emulsion is indicated by what

A
  • oxidation or hydrolysis of the oil or emulsifier
  • change in pH
  • increase in FFA content
  • rancidity of the oil
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62
Q

What does exposure to excessive heat or extreme cold do to an emulsion? (think stability)

A

Freezing: can result in increased oil droplet size
Heat: accelerated hydrolytic degradation

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63
Q

Emulsions stored under nitrogen and not exposed to direct sunlight are likely to exhibit oxidative degradation: T/F

A

False. They are UNlikely to exhibit oxidative degradation when stored this way.

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64
Q

Microfluidization

A

The process of forcing the emulsion through a filter to make sure we are only getting products of a certain size. The filter will catch particles who’s size is too large.

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65
Q

The more you run an emulsion through a filter, the smaller the particle size you will end up with: T/F

A

True.

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66
Q

Emulsions with particles ranging from 3-5um are utilized more rapidly by the body than emulsions with 0.5-1.0um particles: T/F

A

False. Is the opposite.

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67
Q

Production of emulsions

A
  • Start by treating the oil and water phases separately
    1) filter the oil phase. All you need to do
    2) Mix water and any tonicity agents/additives with the emulsifier selected. Adjust the pH, homogenize, and filter this solution
    3) Mix the oil and “water” phases together
    4) disperse and homogenize the emulsion
    5) Do the final pH adjustment (to 8) of the product and filter it.
    6) Pour emulsion into a container, seal, and sterilize
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68
Q

Quality control: ideal particle size for injectable emulsions

A

0.2-0.5um (or can say 0.5-1.0um)

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69
Q

Higher surface charge is preferable for the emulsions to be most stable: T/F

A

True

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70
Q

When might we include a preservative in an injectable emulsion?

A

Can be present to prevent microbial growth if the injectable will be used a few times instead of given one single time in one dose.

71
Q

Clinical uses of injectable emulsions

A
  • Hospital applications
  • Can be used to prepare total nutrient admixtures
  • administered mostly by IV injection
72
Q

T/F: emulsions for injection should be stored in the fridge

A

T

73
Q

Describe hospital dispensing of injectable emulsions

A
  • IV lipid emulsions can be administered in combo with dextrose and amino acids (nutrition)
  • drugs are generally not added to the admixtures, with rare exceptions (ex: heparin, insulin, ranitidine)
  • Physical stability is always the major concern. Don’t want phase separation or precipitation
74
Q

T/F: injectable suspensions are typically given IV

A

False. Don’t want to give large particles by IV so is normally done by IM or SC

75
Q

describe injectable suspensions

A

heterogenous systems consisting of a solid phase dispersed in a liquid phase that may be either aqueous or non-aqueous.

76
Q

Required characteristics of injectable suspensions

A
  • sterile
  • pyrogen free
  • stable
  • resuspendable
  • syringeable
  • injectable
  • isotonic
  • non-irritating
77
Q

T/F: injectable suspensions are the most difficult formulation to develop in terms of stability and production

A

T

78
Q

Ideal particle size for inj. suspensions

A

less than 5um

79
Q

Injectable suspensions: flocculating/suspending agents

A
  • controlled flocculation to form loosely-bound flocs that can easly be redispersed upon agitation.
  • this approach reduces syringeabillity so use is limited in parenteral suspensions
80
Q

Common flocculating agents

A

electrolytes, surfactants, hydrophilic colloids

81
Q

Injectable suspensions: wetting agents

A
  • One of the most important aspects of a suspension b/c the hydrophobic powders are often suspended in aqueous systems
  • wetting agents reduce contact angle btw the surface of the particle and the wetting liquid
82
Q

Injectable suspensions: solvent system

A
  • choice of solvent system depends on solubility, stability and desired release characteristics of the drug.
  • water is the preferred solvent
83
Q

Give examples of non-aqueous water-immiscible vehicles that may be used for suspensions (aka what lipid vehicles can you use to suspend water-soluble particles)?

A
  • ethyl oleate
  • isopropyl myristate
  • benzyl benzoate
  • sesame oil, peanut oil, castor oil
84
Q

Injectable suspensions: other excipients

A

Can include preservatives, tonicity agents, antioxidants, and chelating agents

85
Q

Injectable suspensions: syringeability/injectability

A

These two characteristics refer to the ability of the suspension to pass through the needle before and during the injection.

  • Closely related to viscosity and particle size of the suspension
  • clogging of the syringe needle is not acceptable
86
Q

Injectable suspensions: resuspendibility

A

Describes the ability of the suspension to uniformly disperse with minimal shaking after it has stood for some time.
- Should easily resuspend

87
Q

Resuspendibility of a suspension is related to what properties?

A

particle size, crystal growth, and viscosity of the vehicle

88
Q

Advantages of inj. suspensions

A
  • increase drug stability profiles due to insolubility (drug molecule is more stable b/c it won’t be solubilized)
  • controlled-release action
  • depot release
89
Q

Disadvantages of inj. suspensions

A
  • formulation stability issues
  • difficulty in formulation and production
  • discomfort to patients
  • dose accuracy
90
Q

Name a common chelating agent

A

EDTA acid salts

91
Q

Requirements for optimal injectability of a suspension

A
  • good flow
  • even pressure
  • clogging-free
  • less discomfort
  • viscosity-related
  • excipient-related
92
Q

Requirements for optimal syringeability of suspensions

A
  • passing through needles
  • no clogging
  • dose accuracy
  • <5um particle size
  • 0.5-5% solids
93
Q

Injectable emulsions are usually administered IV and suspensions are usually given IM or SC: T/F

A

True

94
Q

Electrolytes can be added directly to the fat emulsion if needed: T/F

A

False. They should be added last after the two phases are mixed, or can be mixed with amino acid/dextrose injections and then transferred into the emulsion.

95
Q

Medical implants are another form of parenteral drug delivery system: T/F

A

T

96
Q

Oils for injection: requirements

A
  • purity
  • biodegradability
  • IM injection only if oil used as a vehicle
  • IV injection if oil part of an emulsion
  • mainly for steroids, hormones, and vitamins
97
Q

Disadvantage of medical implants

A

require special admin procedures such as insertion and removal. Not all patients are willing to do this AND not all patients can.

98
Q

Describe pyrogens

A

fever inducing agents

  • can result in shock and death
  • rise in temp of more than 0.6 degrees C
  • Ex: bacterial LPS
99
Q

A medical implant drug delivery system must fulfill one or more of 7 requirements. List them

A

1) to facilitate patient compliance by using the device designed for extended and effective therapeutic Tx
2) to deliver drug at a controlled rate throughout the treatment period with minimal AE’s
3) to be readily implanted or inserted w/o major surgical procedures on the patients
4) to be free of potential medical complications w/o requiring supervision by HCPs
5) to possess minimal risk of misuse or unauthorized termination of medication by non-HCPs
6) to be readily retrievable by HCPs when necessary
7) to be manufactured with simple processing and low cost

100
Q

Briefly describe a pharmaceutical implant

A
  • devices in dermal/subdermal tissues for extended period of time
  • sustained drug release profiles
  • alternatives for long-term drug uses
  • surgical implant and removal
101
Q

Characteristics of medical implants: advantages

A
  • long-term actions
  • steady [drug]
  • one administration
  • various drug release mechanisms
  • compliance
102
Q

Characteristics of medical implants: disadvantages

A
  • surgical procedures
  • complications
  • difficult retrieval
  • inflexibility
  • complex production
  • high unit cost
103
Q

Objectives of medical implants

A
  • delivering controlled drug release
  • simplifying admin procedure
  • minimizing medical implications
  • reducing unauthorized misuse of drugs
  • improving patient compliance
104
Q

List the 7 different drug release mechanisms of medical implants

A

1) membrane permeation controlled devices
2) matrix diffusion controlled
3) membrane-matrix hybrid
4) microreservoir partition controlled
5) Osmotic pressure activated
6) vapor pressure activated
7) magnetically activated

105
Q

MODR of membrane permeation controlled implants

A

Drug reservoir is totally enclosed by a rate-controlling polymeric membrane

106
Q

MODR of matrix diffusion controlled implants

A

Drug reservoir is formed by the HOMOGENOUS dispersion of drug solid particles throughout a lipophilic or hydrophilic polymer matrix.

107
Q

MODR of membrane-matrix hybrid controlled implants

A

Combines the two drug release mechanisms. It aims to take advantage of the constant drug release rate maintained by the permeation-controlled system while minimizing the risk of dose dumping (ie premature release of drug) from the reservoir compartment.
- Drug release by both permeation and diffusion

108
Q

How do you formulate the membrane-matrix hybrid?

A

Drug reservoir is initially formed as drug matrix, but then the matrix is encapsulated by a rate-controlling polymeric membrane to form a sandwich-type delivery device.

109
Q

MODR of microreservoir partition controlled implants

A

Presence of many drug reservoirs (mini or microreservoirs) dispersed and suspended in a water-miscible polymer matrix.

110
Q

Is zero-order release possible with a partitioned controlled release system?

A

Yes!

111
Q

MODR of osmotic pressure activated implants

A
  • Osmotic pressure is used as the NRG source to activate and modulate the delivery of drugs from this type of device.
  • Drug reservoir is either a solution or semisolid formulation, and is contained within a semipermeable housing with controlled water permeability.
  • Drug release rate is controlled by water permeability, surface area, and thickness of semipermeable membrane
112
Q

Pre-programming of an osmotic pump can be done to deliver a constant drug dose for an extended time period: T/F

A

True

113
Q

MODR of vapor pressure activated implants

A
  • Vapor pressure acts as the power source
  • Drug reservoir exists as a solution and is contained inside an infusate chamber
  • vapor pressure chamber contains a vaporizable fluid such as a fluorocarbon
  • the fluorocarbon vaprizes at body temp and creates pressure to force the drug solution out of the system
114
Q

MODR of magnetically activated implants

A
  • electromagnetic nrg is used as the power source to activate drug delivery and to control drug release rate.
  • a magnetic wave-triggering mechanism is incorporated into the device, and the drug can be triggered to release at varying rates depending on the magnitude and duration of electromag. nrg applied.
115
Q

How is drug released from magnetically activated implants under ‘non-triggering’ conditions?

A

Releases drugs at a controlled basal rate by diffusion alone.

116
Q

Define liposome

A

A structure consisting of one or more concentric spheres of lipid bilayers separated by water or aqueous buffer compartments

117
Q

What are multilamellar vesicles (MLVs)?

A

Liposomes containing multiple lipid bilayers

118
Q

What are small unilamellar vesicles (SUVs)?

A

vesicles containing only a single bilayer with diameters ranging from 25-50 nm

119
Q

What are large unilamellar vesicles (LUVs)?

A

Liposomes with a single bilayer but with a larger diameter size of 100-500 nm

120
Q

The materials used to prepare liposomes are normally lipids from natural sources. List two

A
  • Phospholipids

- sterols/cholesterol

121
Q

Describe phospholipids

A

Glycerol containing phospholipids are the most commonly use component of liposome formulations.
- phospholipids represent 50% of the weight of a biological membrane

122
Q

Describe phosphatidic acid

A
  • the phosphate moiety carries a double negative charge only at high pH
  • occurs in small amounts in nature as an important intermediate in the biosynthesis of phosphoglycerides
123
Q

What are the most abundant phosphatides in plants and animals?

A
  • Phosphatidylcholine (PC) aka LECITHIN

- phosphatidylethanolamine (PE or cephalin)

124
Q

Arrange from largest to smallest vesicle size: MLV, SUV, LUV

A

LUV, MLV, SUV

large unilamellar, multilamellar, small unilamellar

125
Q

List 3 important roles cholesterol has in liposome structures

A

1) decreasing the fluidity or microviscosity of the bilayer
2) reducing the permeability of the membrane to water soluble molecules
3) stabilizing the membrane in the presence of biological fluids such as plasma

126
Q

What happens if we don’t add cholesterol to liposomes?

A

Liposomes w/o cholesterol tend to interact rapidly with plasma proteins such as albumin, transferring and macroglobulins. This typically destabilizes the bilayer.

127
Q

Why do liposomes have high in vivo tolerance?

A

The structural components of liposomes (phospholipids, cholesterol) will be treated the same way as naturally synthesized biological membranes and are broken down accordingly.

128
Q

Liposomes carry polar or nonpolar drugs?

A

Both! Polar drugs sit in the aqueous compartment, and nonpolar drugs will sit in the lipid bilayers

129
Q

Why may we potentially want to incorporate charged lipids into liposome bilayers?

A

Charged lipids increases the volume of the aqueous compartments by separating adjacent bilayers due to charge repulsion. This results in volume increase where we can potentially fit more drug.

130
Q

For hydrophopic (lipid soluble) drugs, liposomal entrapment efficiency usually approaches 100% almost irrespective of liposomal type and composition: T/F

A

True

131
Q

Why are small nanoparticles (under 10nm) potentially toxic?

A

they can enter mitochondria of cells

132
Q

Give an example of a typical liposome formula

A
  • Egg lecithin (phosphatidylcholine); 45%
  • Phosphatidylserine: 9.9%
  • Cholesterol: 45%
  • a-tocopherol (antioxidant): 0.1%
133
Q

Lecithin (phosphatidylcholine) is the most frequently used lipid for liposome formulation. What is a disadvantage?

A

Shows potential chemical instability

134
Q

Why is Sphingomyelin sometimes substituted for lecithin in liposomes?

A

it produces more rigid membranes, which are though to have longer half lives

135
Q

What is the role of phosphatidylserine in liposomes/

A

Thought to impart a charge on the liposome. This can potentially be used in specific targeting of liposomes

136
Q

Why is an antioxidant included in the recipe for liposomes?

A

To prevent oxidation of unsaturated phospholipids

137
Q

One of the things holding back liposomes is in vivo stability. Describe

A
  • various interactions in vivo: example opsonisation by immune cells
  • instability due to protein transfer: the lipid bilayer isn’t entirely fixed so proteins can sometimes travel in and out
  • Size and preparation related
  • drug loss can be dramatic
138
Q

List 3 liposome preparation methods and briefly describe

A

1) hydration method: introduction of an excess volume of aqueous buffer to a thin film of lipids under reduced pressure
2) solvent injection method: injection of lipids dissolved in an organic solvent (eg ether) into a vast volume of buffer solution
3) reverse phase evaporation method: formation of a W/O emulsion of phospholipids and buffer in excess organic phase, followed by removal of the organic phase under reduced pressure

139
Q

Describe the creation of stealth liposomes: their purpose and the common protectand used

A
  • created to try and hide from the immune system (prevent opsonisation). This increases retention time, half life and stability
  • Protectant: commonly PEG, doesn’t trigger immune cells
  • stealth liposomes allow more drug to reach the target for therapeutic efficacy
140
Q

What is the optimal filter size for sterilization of liposomes?

A

0.22 microns

141
Q

Why is the optimal filter size for liposome sterilization 0.22 microns?

A

Most pathogens are larger than this, so we filter them out.

142
Q

What are physical stability issues of liposomes?

A
  • dynamically instable
  • particle aggregation
  • particle fusion
  • phase change
  • drug leaching
143
Q

What are chemical stability issues associated with liposomes?

A
  • hydrolysis
  • oxidation
  • pH
  • membrane permeability
  • drug delivery
144
Q

Why should liposomes be stored in the fridge?

A

Prevents from environmental hazards: light and hot temps “denature” them

145
Q

How does reactions with albumin in vivo contribute to liposome instability?

A

Transfer of bilayer lipids to albumin and HDL’s can occur. In addition, some proteins are also transferred from the lipoprotein to the liposomes

146
Q

In general, SUV liposomes are the most stable: T/F

A

False. MLVs are the most stable as only a portion of the phospholipid is exposed to in vivo attack.
SUVs are the least stable due to stresses imposed by their curvature

147
Q

T/F: incorporation of charged lipids into the bilayer increases stability in plasma

A

False. Charged lipids decrease stability in plasma

148
Q

Why are liposomes so promising?

A

They can act as: a disperser for drugs that are difficult to solubilize, a sustained release system for microencapsulated agents, penetration enhancers, and site-specific delivery vehicles.

149
Q

Liposomes tend to accumulate in organs like the heart and kidneys: T/F

A

False.

150
Q

T/F: liposomes can be administered via all routes, incl. parenteral, topical, oral, pulmonary

A

T

151
Q

Sterilization of liposomes

A
  • Microbial-retentive filtration for final sterilization
  • filtration should not affect liposome structure
  • thermal and radiation sterilization could compromise structure integrity and drug activity
  • aseptic manufacturing is expensive and difficult in validation
152
Q

Liposome disadvantages

A
  • instability
  • high material cost
  • large-scale production difficulties
153
Q

Medical applications of liposomes

A
  • site-specific delivery
  • site-avoidance delivery
  • sustained/controlled drug release
  • passive drug targeting to tumors
  • protein/peptide/gene delivery
154
Q

Liposomes have achieved their largest impact thus far in cosmetics: T/F

A

T

155
Q

Polymeric dispersions

A
  • microcapsules
  • microspheres
  • nanocapsules
  • nanospheres
  • nanoparticles
156
Q

Differentiate between nano and micro

A

Micro: 1-1000 um
Nano: 10-1000 nm

157
Q

Besides liposomes, ______ are the other colloidal systems that possess controlled drug release profiles and site-specific targeting characteristics

A

nanoparticles

158
Q

define nanopaticle

A

colloidal particles with a size smaller than 1mm

159
Q

Differentiate btw nanocapsules and nanospheres

A

Capsules: have a core-shell structure (a reservoir system)
Spheres: represent a matrix system

Nanoparticle is used as the general term for both of them because it can be hard to distinguish between their structures

160
Q

The techniques used to prepare nanoparticles are classified in two groups. Describe.

A
  • First, nanoparticles are formed from preformed polymers. The polymers include both water soluble and insoluble polymers of synthetic or natural origin.
  • Second, nanoparticles are prepared through various polymerization reactions of lipophilic or hydrophilic monomers
161
Q

List a few procedures that may be employed in preparing nanoparticles

A
  • emulsion-evaporation method
  • salting-out method
  • emulsion-diffusion method
  • precipitation method
  • preparation of nanocapsules
162
Q

T/F: nanoparticles can be prepared from direct polymerization of monomers

A

T

163
Q

Most nanoparticles are designed for pulmonary admin by aerosol: T/F

A

F. Most are designed for parenteral admin.

164
Q

Why is a purification step critical when building nanoparticles?

A

Need to separate nanoparticles from some components (both undesirable and toxic) used in their preparation such as organic solvents, surfactants, polymer aggregates, electrolytes, and stabilizers.

165
Q

Difficulties associated with nanoparticles

A
  • use of organic, toxic solvents
  • operator protection
  • envr pollution/protection
  • large scale production difficulties
  • production cost
166
Q

List a few ways to purify nanoparticles

A

1) Ultracentrifugation
2) Centrifugal ultrafiltration
3) Cross-flow filtration
4) Gel permeation
5) Dialysis

167
Q

A drying step is useful but not required in the preparetion of nanoparticles: T/F

A

F. Drying step improves the physicochemical stability of the nanoparticles

168
Q

Describe drying of nanoparticles

A

Freeze-drying is the most common method, where nanoparticle suspensions are frozen at low temps or in liquid nitrogen. Can use a cryoprotective agent (dextrose, lactose, mannitol, sucrose) if necessary

169
Q

What is the sterilization method of choice for nanoparticles?

A

gamma radiation

170
Q

Why are heat and ethylene oxide gas inappropriate for sterilizing nanoparticles?

A

Heat causes irreversible fusion of nanoparticles.

Gas will result in excess residual concentrations within the products.

171
Q

Drug release from nanoparticles

A
  • hydrophilic polymers facilitate faster drug release than lipophilic polymers
  • drug solubility, diffusivity, molecular weight and particle size influence drug release rate and extent
  • controlled release is achievable by formulation strategies
  • Drug release can happen due to change in temperature when it is absorbed in the human body
172
Q

How can you evaluate a new compound that is developed?

A

Biological studies in vitro (lab) and in vivo (animal pre-clinical and human clinical trials)

173
Q

Describe in vitro evaluation of nanoparticles

A
  • interaction with blood components
  • uptake by cells
  • stability
  • toxicity
174
Q

Describe in vivo evaluation of nanoparticles

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

Ceutics final (2 decks)

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