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week 21 > the medicine > Flashcards

the medicine Flashcards

1
Q

List three types of emulsifying agent

A

surfactant
Hydrophilic colloids
Finally, divided solid particles

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2
Q

List three factors, which influence emulsion viscosity

A

Oil to water ratio
Globule size
emulsifier used

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3
Q

List two examples of factors which can cause chemical instability

A

change in pH
Electrolytes

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4
Q

what factors should be considered when choosing a preservative for an emulsion

A

Its concentration in aqueous phase, which is related to its partition coefficient

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5
Q

what is the definition of a stable emulsion

A

One of which the dispersed globules retain their initial character, and remain uniformly distributed throughout the continuous phase

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6
Q

give 4 methods of stability testing

A

microscopic examination
Global size analysis
Viscosity changes
Accelerated stability testing

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7
Q

What is macroscopic examination?

A

Measure the degree of creaming or sedimentation occurring over time

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8
Q

What is globule size analysis?

A

If global size increases a number of globules decrease. Coalescence is occurring. This will cause an increased rate of creaming/sedimentation.

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9
Q

What is viscosity changes?

A

any change in globule size, number or position may be detected by a change in viscosity

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10
Q

What is accelerated stability testing?

A

centrifugation
Storage at adverse temperatures

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11
Q

experimental determination of the optimum HLB

A

using 2 surfactants, prepare a series of emulsions, with varying HLB values

The system with minimum creaming or separation of phases has the optimum HLB

And measure the mean, globule size using laser, diffraction methods

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12
Q

What does an increase in temperature: decrease apparent viscosity of continuous phase lead to

A

increased creaming

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13
Q

temperature increase: increase kinetic motion of dispersed, droplets, more globules, Collide leads to

A

Increased creaming

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14
Q

Temperature increased: increasing kinetic motion of emulsifying agent at interface. This can weaken the film leading to.

A

Coalescence

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15
Q

freezing, an oil and water emulsion leads to ice, and crystals, forming in the aqueous phase. This leads to

A

exerting, unusual pressures on the adsorbed emulsifier film

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16
Q

freezing and oil in water emulsion. The dissolved electrolyte may concentrate in the unfrozen water. This may lead to

A

Affecting the film charge density

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17
Q

What may not give the same degree of stability at the required HLB

A

not all emulsion combinations

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18
Q

mineral oil emulsions have been used to treat constipation

However, the use has been discouraged, because

A

The emulsion may reduce absorption of oil, soluble vitamins

Very small mineral oil globules may be absorbed into the bloodstream

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19
Q

emulsion drug delivery: GIT absorption

A

A drug most dissolve in the aqueous fluid of the GIT prior to absorption

But the drug must still be sufficiently lipophilic to allow partitioning across the lipid membrane of the cells

If delivered in an oil, the drug can be absorbed by the same route as an ingested fat

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20
Q

what are micro emulsions

A

globule size of 5-140nm
The form spontaneously when components are mixed at the appropriate ratio

These are thermodynamically stable

They employ a high concentration of surfactant

They are often called swollen micelles

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21
Q

give an example of a micro emulsion

A

sandimmune neoral

commercially available from novartis

It’s gives a higher rate of absorption
A shorter residence time

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22
Q

what is a self emulsifying system

A

these are mixtures of oil and surfactant that form emulsions on mixing with water with little or no energy input

They can form spontaneously, on addition of one phase to the other

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23
Q

What is the parenteral route?

A

injectable formulation of lipophilic drugs

Parenteral nutrition: provides nutrition, especially calories by parenteral route

fat emulsions O/W with mean globule size of 200-300nm

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24
Q

Tell me about parenteral nutrition

A

patients who must be fed parenterally over a longer period of time need amino acids, electrolytes, trace, elements, and vitamins, as well as calories.

All in one products are available

Due to numerous components, there is often unexpected interactions

Often supplied as a multi bag system

Before application, the components are mixed and extra vitamins and trace, elements can be given

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25
Q

what does this recommendation mean?

Additives may only be added to fat emulsions when compatibility is known

A

IV fat emulsions may break down with coalescence of fat globules and may separate with addition of antibiotics for electrolytes. Therefore, there is an increased risk of emobolism

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26
Q

what is intralipid as an IV drug carrier

A

lipophilic drugs can be dissolved in the soya bean oil

This is an alternative to solubilising the drug in cremophor EL

examples include: diazepam and propofol

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27
Q

Describe an accelerated stability test you could employ to check for creaming

A

centrifugation or
Increasing temperature

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28
Q

describe two advantages of micro emulsions

A

increased stability
Can provide an increased bioavailability

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29
Q

skin overall

A

it is the largest organn
Containment of fluids and tissues
Regulate heat and water loss
Acts as a barrier to chemicals and micro organisms
Consists of three functional layers

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30
Q

what is the hypodermis

A

subcutaneous, fat, layer
It is relatively thick
Insulates the body
Protects against shock
energy source
Contains blood vessels and nerves

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31
Q

what is the dermis

A

major component of human skin
3-5 mm thick
support and elasticity
Extensive vasculature
Regulates temperature
Delivers oxygen and nutrients
Removes toxins and waste

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32
Q

what are the epidermis layers?

A

The outermost layers
0.1-0.2mm thick
Provides protection
Cell renewal (lifetime is four weeks)
avascular
Stratum corneum forms the rate controlling barrier

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33
Q

What is the stratum corneum?

A

formed like bricks and mortar
Dead, flattened keratin rich cells (corneocyte)
Intracellular lipids (bilayer arrays)

34
Q

What is the main barrier to drug absorption across the skin?

A

Stratum corneum

35
Q

What are the three main layers of the skin?

A

Hypodermis
Dermis
Epidermis

36
Q

What are advantages of transdermal drug delivery?

A

The avoidance of a significant presystemic metabolism (gastrointestinal tract, or by the liver)

Lower daily dose

You can avoid multi dozing

Extend the duration of drug action, reduces frequency of dozing

Improve patient, compliance and acceptability

Simple removal of dose

37
Q

What are disadvantages of transdermal drug delivery?

A

skins barrier function limits the drug absorption

not all drugs are candidates

Variation in permeation rate
Race, age, environmental history

Irritation and sensitisation at the site of administration or application

38
Q

Target to regions: surface

A

to generate a protective layer or attacking bacteria/fungi

Protective films or sunscreens to hinder moisture loss

Topical antibiotics, antiseptic’s and deodorant to kill surface micro organisms

39
Q

Target regions: stratum, corneum

A

how to improve emollience by raising water content
Creams and ointments to enhance the moisture
Stimulate sloughing (removal of dead cells)
Salicylic acid

Ideally, should not enter viable tissue

40
Q

Target regions: viable, epidermis, and the dermis

A

can treat many diseases provided the drugs can be delivered to the receptors efficiently

Steroids and non-steroidal anti-inflammatory agents

Anaesthetic drugs to reduce pain

Antihistamines to alleviate itch

41
Q

Target regions: skin appendages hair, follicles and sweat glands

A

known as a shunt route(by passes stratum, corneum)

High permeability

Low surface area

Antiperspirant to reduce hyperhidrosis of sweat glands

Barium sulphite as dipilarories

42
Q

Target regions: systemic

A

can treat several conditions

Travel sickness (hyoscine)
Hypertension (clonidine)
Smoking (nicotine)
Pain (Fentanyl)

Limited due to low delivery efficiency

43
Q

what are routes of absorption?

A

mostly via transepidermal

Need to circumvent the stratum corneum

44
Q

Transepidermal route: transcellular route

A

though horny cells

45
Q

trans epidermal route: intracellular route

A

avoids horny cells through lipid matrix instead

Predominant, diffusional path

46
Q

What are optical drug characteristics?

A

small molecular weight
Lipophilic
Low, melting point (good solubility properties)
Hydrogen bonds (interaction with pull ahead, groups of lipids in the skin/reaches plateau)
pKa (unionised fraction).

47
Q

what is flux

A

The rate of diffusion across a permeable membrane

48
Q

what is the octagonal water partition coefficient

A

LogP(Octanol/water) > 3 is highly lipophilic
LogP(Octanol/water) 1-3 is intermediate
LogP(Octanol/water) <1 is hydrophillic

49
Q

When do you get the best absorption?

A

from small and lipophillic molecules

50
Q

What is the pH partition hypotheses?

A

many drugs are weak acids or bases
un ionised molecules partition into lipid membranes
ionised ones do not
Transdermal absorption of weak electrolyte is favoured by the unionised form

51
Q

what are the two routes of absorption through skin?

A

Transcellular
Paracellular (main route)

52
Q

What are the optimal drug characteristics for transdermal delivery?

A

small molecular weight
Lipophilic
Hydrogen bond formation
Low, melting point
unionised

53
Q

Give examples of dermatological formulations

A

liquid preparations
gels
Powder
ointments
Creams (O/W W/O)
Pastes

54
Q

what are creams

A

O/W or W/O
emulsions for topical administration

55
Q

creams O/W properties

A

less greasy feel and a more pleasant to use
Easy rinsing from the skin
Variations, in consistency form fluid lotions to viscous creams
popularity with patients
prone to microbial contamination
As the continuous phase evaporates, concentration of water, soluble, drug increases, promoting absorption
non occlusive
It deposit slip it, and other moisturises on the skin, resulting in the skins hydration
Requires mixed emulsifiers (surfactant and fatty acids)

56
Q

creams W/O properties

A

emollient cleansing agents
use w/o emulsifying agents

57
Q

what is an ointment

A

A greasy semisolid a system that is applied externally (skin and mucosal membrane)

Formulation involves dispersion or dissolution of a medicament into an ointment base

Physio chemical properties of the drug and ointment base are so crucial

58
Q

what are choices of ointment base

A

dependent on several factors:
Site of application , occlusion
Rate of drug release: solubility and diffusion of drug
Drug stability: hydrolysis is reduced in the hydrophobic base
rheology: effect of drug inclusion

59
Q

what are hydrocarbons bases?

A

hard, soft, liquid paraffin
Properties:
They form, thick, occlusive films
Sticky feel
Difficult to remove from skin
Variation inconsistency with temperature change
Tend to be poor solvents

60
Q

What are silicones?

A

have similar properties to hydrocarbons
Dimethicone
Water repellent with low surface tension
Barrier creams to protect against water, soluble irritants
Nappy rash, bedsore, inconsistence

61
Q

What are absorption bases?

A

less occlusive than hydrocarbons
Non-emulsified
Absorb water to form W/O emulsions
Inclusion of low, HLB surfactants (W/O emulsifying agent)
W/O emulsions

62
Q

What are emulsifying bases

A

anhydrous bases containing O/W emulsifying agent (HLB values of 9-11) so they are water, miscible, washable, or self emulsify

Emulsifying ointment

63
Q

What are water soluble bases?

A

mixtures of high and low molecular weight polyethylene glycols

They have an ointment like consistency, non greasy

Soften and melt onto the skin

Unable to incorporate large volumes of aqueous solutions

Reduce the antimicrobial activity of quaternary, ammonium, compounds.

64
Q

What is a paste?

A

up to 50% of the powder is dispersed in an ointment base

can localise the action of an irritant or staining materials

forms and opaque film (sunblock)

65
Q

what is a gel

A

semisolid systems, in which there is an interaction between colloidal particles with a liquid vehicle

Can be based on:
type 1: dispersed, solids (network of flocculation)
type 2: hydrophilic, polymers

66
Q

what are type 1 gels

A

hydrogels
Covalent interactions mediated by cross-linkers
Don’t flow when stress is applied
Able to absorb a considerable mass of water
Used as a wound dressings and sustained release implants

67
Q

what are type 2 gels

A

most common
Have a weak bonds (Vander walls, ironic, hydrogen bonding)
Application of stress leads to temporary reversible destruction of interactions
pseudoplastics

68
Q

Why is formulation choice important?

A

liquid: rapid, short term, input of permeant
Semisolid: increased resistance
Patches: extended drug delivery

69
Q

why would you expect creams or ointments to have a longer shelf life and why?

A

ointments – lack of water phase; generally improve physical, chemical, and microbial stability

70
Q

The choice of ointment base depends on:

A

site of application
Drug, release and stability
rheology

71
Q

What is permeability enhancement?

A

It is the improvement or increase in the permeability of a material or substance.

72
Q

What are some materials that increased permeability enhancement?

A

permeability, enhancing excipients
Supersaturation
Liposomes
Microemulsions
Lipid nano particles

Generally localised effect in the stratum corneum

Prodrugs

73
Q

What is physical permeation enhancement?

A

Needles?
Obvious and most straightforward method
Long history of use

Disadvantages:
Pain
Psychological
Infection risk

74
Q

What are minimally invasive methodologies?

A

tape stripping
suction ablation
iontophoresis
Electroporation
Sonophoresis
High velocity particles
Laser assisted delivery
Micro needles

75
Q

What is tape stripping?

A

simply remove barrier
An adhesive tape removes sequential layers of the stratum corneum
Hydration (occlusion) helps
Cumbersome and uncontrolled

76
Q

what is suction ablation

A

removal of the stratum corneum by suction blister formation

Application of vacuum to select an area

Create a portal for drug delivery at stratum lucidum

Pain-free?

77
Q

what is iontopheresis

A

transfer of charged substances under the influence of an electric field

Enlarges range of drug candidates, particularly Polar and or charged particles

Acts on molecules themselves

78
Q

what is electroporation

A

A large voltage treatment over a short period of time

Producers transient hydrophilic pores

Universal physical phenomenon of lipid bilayers

79
Q

what is sonopheresis/phonophoresis

A

It’s uses ultrasonic energy
Formation and subsequent collapse of gas bubbles (cavitation)
Temperature elevation

80
Q

What are high velocity particles

A

compressed gas blast fine particles through the skin

Useful for larger, macromolecules (vaccines)

Drug may be coated on particles

Pain-free, but worry free?

81
Q

What is Laser assisted delivery?

A

there are two processes:

ablative: high energy forms pores
optoacoustic: stress wave transiently increases permeability

Hydrophilic and lipophilic drugs
Well controlled

82
Q

What are micro needles?

A

they pierce the upper epidermis
They do not reach nerve receptors
They can be solid or hollow
They are generally silicone
They are fabricated by wet etching

Nanovic technology

coated microneedle – usually stainless steel arrays coated with a formulation containing drug

Polymeric, micro needles – higher resilience, can provide improved, drug release pattern because of the polymers degradation and dissolving capabilities

week 21 (3 decks)

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