Formulation of Rheology Flashcards
(60 cards)
1
Q
What is rheology?
A
Describes a mixture of viscous & elastic events.
2
Q
What does viscosity measure - 3
A
- Viscosity measures resistance to flow
- Greater viscosity = greater resistance
- Viscosity: temp dependent, decreases when temp increases.
3
Q
Newton’s law of flow - 2
A
- Consider liquid as a block consisting of parallel plates of molecules.
- When bottom layer is fixed in place & the top plane of liquid is moved at constant velocity each lower layer moves with a velocity directly proportional to its distance from the stationary bottom layer.
4
Q
Shearing stress - 2
A
- Rate of force required per unit area to produce the shearing of molecules is called the shearing stress - F/A
- Rate of shear = dv/dr
5
Q
What is liquids fluidity - 2
A
- Liquids fluidity: measure of n/density
- Describe how much fluid resists flow under the force of gravity.
6
Q
What makes a system non-newtonian - 2
A
- If curve is nonlinear for all shear rates tested.
- Newtonian systems have a linear, simple rheogram.
7
Q
Non-newtonian systems are - 2
A
- When materials properties of viscosity & elasticity change in response to shear rate
- Classes: Plastic, Pseudoplastic & Dilatant
8
Q
Plastic flow - 5
A
- Flow does not begin until a shearing stress corresponding to the yield value is exceeded.
- If stress is below the substance, acts as an elastic material (remain a solid)
- Yield value exists due to contacts between adjacent particles (via Van Der Waals forces).
- These must break down before flow can occur.
- Typically associated with flocculated particles present in concentrated suspensions.
9
Q
Pseudoplastic flow - 6
A
- Rheogram for a pseudoplastic material begins at origin
- No yield value.
- No part of curve is linear, so pseudoplastic material can’t expressed by any single value.
- Viscosity of pseudoplastic substance decreased with rate of shear,
- The apparent viscosity at any shear rate = slow of tangent to curve a specified point.
- Orientation reduces internal resistance of material & allows greater rate of shear at each successive shearing stress.
10
Q
Dilatant flow - 4
A
- Suspensions w/ high % of dispersed solids exhibits increased resistance to flow w/ increasing rates of shear systems.
- Volume increases when sheared. Once stress removed dilatant system returns to original state of fluidity.
- Substances w/ flow property contain a [high] of small & deflocculated particles.
- At rest particles closely packed w/ minimal inter-particle volume, voids. Vehicle used to fill voids, allowing particles to move relative to one another at low rates of shear.
11
Q
Rheopectic fluids - 4
A
- Similar to dilatant, when shear is applied, viscosity increases.
- Key difference: viscosity increase is time dependent - can be stimulated with agitation.
- When shaken fluid becomes thick or even possible solidifies. The higher the shear stress, the more viscous that fluid becomes.
- Rheopectic fluids constructed under continuous shearing also called shear-induced crystallization.
12
Q
Thixotropy - 4
A
- A reversible time-dependent decrease in viscosity.
- Shown as slow recovery of viscosity & shearing
- Quantified by area of hysteresis between curves.
- Only applied to shear thinning systems
13
Q
Applications of thixotropic behaviour - 4
A
- Utilized in applications of creams & lotions.
- Viscosity decreases upon shearing
- Subsequent slow increase
- Can be manipulated to provide better application experience.
14
Q
Gel
A
Viscous elastic solid-like materials comprised of an elastic cross-linked network & a solvent.
15
Q
Gel features - 3
A
- Large increase in viscosity above gel point
- Appearance of rubber-like elasticity
- Gel retains shape under low stress but deforms at higher stress
16
Q
Hydrogel - 4
A
- Retain sig amount of H20, but water-insoluble
- Drug diffusion rate in hydrogel depends on physical structure & chemical nature of the polymer network
- If highly hydrated diffusion occurs through the pores
- If low hydration then drug dissolves in the polymer & is transported between the chains
17
Q
Crosslinking of hydrogels - 2
A
- Increases hydrophobicity of a gel
- Decreases the diffusion rate of the drug
18
Q
Swelling & drug release in hydrogels - 2
A
- Swelling characteristics of polymeric gel changeable by heat, pH or electrical current
- Results in responsive drug delivery - being able to switch on and off.
19
Q
Macromolecular crosslinking - 2
A
- Can result from physical interactions or chemical cross-linking.
- When gels are formed by strong chemical bonds they cannot be dissolved & are thermally irreversible. Weak non-covalent interactions are reversible.
20
Q
Type 1 gels - 3
A
- Irreversible systems
- 3D network formed by covalent bonds between macromolecules.
- Formed by polymerisation of monomers of water soluble polymers in presence of x-linker.
21
Q
Type 2 gels - 4
A
- Heat reversible
- Held together by intermolecular bonds.
- Gel on cooling below T=gel point.
- solutions in water are viscous so gelling properties suitable for use in topical applications to skin. Gel dries rapidly, leaving plastic film with drug in contact with the skin.
22
Q
What are cross-linked polymeric systems - 2
A
- If water-soluble polymer chains are covalently x-linked into 3D structure the gel formed when a dry material interacts with water.
- The polymer will swell but it cannot dissolve due to x-links.
23
Q
Supramolecular - 2
A
- Gels derived from low-MW compounds.
- Formed through self-aggregation of small molecules to form Self-Assembled Fibrillar Networks (SAFINs) by combo of non-covalent interactions.
24
Q
Supramolecular gel preparation - 5
A
- Heating gelator in solvent & cooling the resulting isotropic supersaturated solution to room temp.
- Once cooled, molecules condense & 3 situations may arise.
- Highly ordered aggregation makes crystals
- Random aggregation results in amorphous precipitate
- Aggregation process intermediate between these two, yielding a gel
25
Liposome orientation - 5
1. Liposomes generated through phospholipids interacting w/ water to form vesicular structures based off lipid bilayers encapsulating an aqueous core.
2. Considered to be liquid crystals.
3. Spontaneously orientate in water to give most thermodynamically stable conformation
4. Typically hydrophilic headgroup facing into aqueous environment so lipid chains orientate inwards avoiding the water phase.
5. To reduce exposure at edges, the bilayers self close into concentric compartments around an aqueous phase.
26
Micelles as drug carriers - 3
Good potential to carry:
1. Strongly lipophilic drugs fully buried in lipid bilayer
2. Strongly hydrophilic drugs sequestered in the aqueous interior of the liposome
3. Drugs with intermediate logP partition between the lipid & aqueous phase can serve as carrier for water & lipid soluble drugs.
27
What do Micelles structural integrity & stability - 6
1. Type & quality of lipids being used.
2. Alkyl-chain length & degree of unsaturation
3. Cholesterols tends to rigidify bilayers
4. Storage condition: light, oxygen & temp
5. Stabilisers e.g. cholesterol, alpha-tocopherol, inert atmosphere
6. Certain formulations lyophilised with retention of contents & diameter
28
What makes liposomes good drug carriers - 5
1. Composed of natural phospholipids
2. Bio-compatible/degradable
3. Biologically inert
4. Weakly immunogenic
5. Low intrinsic toxicity
29
4 classes of liposomes
Conventional liposomes: neutral or -ve. Used for passive targeting of mononuclear phagocyte systems.
Sterically stabilised (‘stealth’) liposomes: carry hydrophilic coatings, used to obtain prolonged circulation times.
Immunoliposomes (‘antibody-targeted’): conventional or sterically stabilized, used for active-targeting purposes.
Cationic liposomes: +ve, used for delivery of genetic material.
30
Immunoliposomes - 3
1. Immunoliposomes have specific antibodies or antibody fragments on their surface to enhance target site binding.
2. Primary use in targeted delivery of anticancer agents.
3. Long-circulating immunoliposomes can also be prepared. Antibody coupled to the liposomal surface, however the PEG chains may provide steric hindrance to antigen binding.
31
Cationic liposomes - 2
1. Cationic lipid components of liposomes neutralize -ve DNA, condensing the DNA into a more compact structure.
2. Depending on preparation method used, complex may not be a simple aggregate, but an intricate structure in which the condensed DNA is surrounded by a lipid bilayer.
32
Adv of nanoparticles - 3
1. Increases drug penetration & stability
2. Too small to be detected by the immune system
3. Delivers drug in target organ using lower doses to reduce S/Es
33
Adv & Dis of liposomes - 5
Adv:
1. Biocompatibility
2. Low toxicity
3. Targeted delivery of drugs to the site of action
Dis:
4. Limited penetrating ability
5. Chemically & physically unstable
34
Transferosomes - 5
1. Ultra-deformable liposomes with a surfactant/emulsifier (edge activators)
2. Destabilizes lipid bilayers of SC & increases deformability by lowering interfacial tension of lipid bilayers.
3. Permeates intact skin by squeezing selves along intracellular sealing lipid of the SC
4. Drug localizes at [higher] in deeper layers of skin
5. Edge activators must be highly pure to avoid skin irritation and toxicity.
35
Ethosomes
Soft lipid vesicles composed of phospholipids, water & ethanol in relatively [high]
36
Binary ethosomes & Transethosomes
Binary ethosomes: addition of another type of alcohol. Most commonly used alcohols in binary ethosomes are propylene glycol (PG) & isopropyl alcohol (IPA).
Transethosomes: Basel ethosomes & additional compound, e.g. penetration enhancer or surfactant.
37
Ethosomes Adv & Dis - 5
Adv:
1. More effective transdermal delivery than classical liposomes
2. Smaller & have higher entrapment efficiency than liposomes
3. Fluidizing effect of alcohol enhancers deformability of vesicles & fluidizes lipid bilayers
4. Shows better skin permeation & stability than classical liposomes
Dis:
5. Skin irritation due to high [alcohol]
38
Adv & Dis solid lipid nanoparticles - 5
Adv:
1. Increases adhesiveness to surfaces
2. Controls the occlusion effect
3. Increasing skin hydration
Dis:
4. Decreased loading capacity
5. Expulsion of drug during storage.
39
Nanostructured lipid carriers - 8
1. Can carry both solid & liquid lipids.
2. Blocks ear
3. Increased Skin Hydration
4. Low toxicity
5. Small particle Size
6. Enhances stability of liable compounds
7. Physical sunscreen on their own - adhesive film on skin
8. Reduce skin irritation
40
Niosomes - 5
1. Bilayered structures of non-ionic surfactant & cholesterol
2. Able to entrap wide range of chemicals
3. Less toxic than carriers with ionic surfactant
4. Limited shelf-life
5. Time consuming preparation process
41
Nanoemulsions: Adv ~& Dis - 7
Adv:
1. Both hydrophilic & hydrophobic drugs can be applied
2. Solubilisation/extraction of SC lipids, decreasing resistance for drug transport
3. Greater & extended cellular penetration
4. Raised efficacy due to increasing surface-to-volume ratios
5. Non-toxic & non-irritant
6. Kinetically stable
Dis:
7. Stability problems
42
Outline colloids & suspensions - 4
1. Particles in a colloid do no settle due to gravity - those in a suspension do settle.
2. Particles in suspension visible to naked eye & separated by filtration, in a colloid must be viewed using a light microscope.
3. Water insoluble materials >1,000nm form a suspension
4. Water insoluble materials <1,000nm form a colloid.
43
Emulsion
Mix where tiny droplets of one liquid are dispersed in another immiscible liquid; Oil-in-water (o/w), water-in-oil (w/o), multiple emulsions (e.g., w/o/w)
44
Differences in emulsion & suspensions
Emulsion: Mix of 2 immiscible liquids, with particles not visible to naked eye & can't be filtered, dispersed in solid, liquid or gas, emulsifying agent required. Freezing leads to cracking. 1-1000nm particles
Suspensions: Mix of 2 substances of any matter, visible particles & can be separated by filtration, dispersed in aqueous or oily liquid, stabilizing agents required. Freezing leads to aggregation. >1000nm particles
45
Colloidal stability - 3
1. Water-insoluble drug in fine dispersion form
2. High SA → High surface energy → Aggregation
3. Thermodynamically unstable two-phase system because particles achieve lower SA (energy state) by flocculating or aggregating
46
DVLO theory - 3
1. At short inter-particle distances, attractive forces predominate (primary minimum) & particles tend to agglomerate,
2. As inter-particle distance increases (i.e., sufficient energy added to separate particles) repulsive forces predominate, & particles remain in suspension (maximum),
3. If inter-particle distance increased further, repulsive force decreases, & particles are weakly attracted (secondary minimum).
Depth of secondary minimum is key to determining the stability of the system.
47
Low electrolyte's effects on colloidal stability - Low, Moderate & High
Low [electrolyte] → total energy curve has large primary maximum but no secondary minimum.(particle repulsion stabilizing the colloid)
Moderate [electrolyte] → has a secondary minimum that permits formation of a stable suspension, flocculation can occur in secondary minimum & modest primary maximum sufficient to prevent coagulation in primary minimum (some attraction forms)
High [electrolyte] → no primary maximum or secondary minimum (repulsion disappears & coagulation destabilises the colloid)
48
Flocculation - 5
1. Prevents rigid cohesion by forming loose aggregates
2. Held together by comparatively weak inter-particulate forces
3. Aid in stability
4. Lattice type structure that resists complete settling, reduces caking, aids re-dispersion
5. Effect of electrolyte on flocculation depends on valence of counterion.
49
Flocculation in stabilizing suspensions - 4
1. In flocculated systems the repulsive barriers have not been reduced, & particles form loosely bonded structure in the secondary minimum region.
2. Particles can settle as flocculates due to flocculation agent causing suspended solids to clump together
3. Sediment not closely packed, & caking doesn't occur
4. Suspension formulations aim for partial or controlled flocculation
50
Controlling flocculation - 2
1. Non-ionic polymers to increase (aq) phase viscosity by using, e.g. natural gums, cellulose polymers
2. By hindering particle movement, there can be an increase in the adsorbed layers on particles, leading to steric stabilisation &/or inter-particle bridging
51
Ideal flocculation agent properties - 5
1. Be easily & uniformly incorporated in formulation
2. Readily dissolve/disperse in water
3. Ensure formation of loosely-packed system that does not cake
4. Not affect dissolution rate or absorption rate
5. Be inert, non-toxic, & free from incompatibilities
52
O/W emulsion - 3
1. Adsorption of surfactant w/ hydrophilic elements at the lipid droplet surface lowers interfacial tension
2. The surfactant monolayer at surface decreases potential for collisions.
3. Non-ionic surfactants adsorb onto oil droplets to increase their stability by creating hydrated layer on hydrophobic particles.
53
W/O Emulsion - 4
1. Hydrocarbon chains of surfactants protrude into oily, continuous phase;
2. Tendency for water droplets to coalesce reduced by deceased area of oil-water contact
3. This stabilizes steric repulsive forces.
4. Mix of surfactants increases stability
54
Comparing surfactants - 2
1. Hydrophile-lipophile balance system establishes a balance between hydrophobic & hydrophilic components of a solubilising agent.
2. HLB values calculated using simple, empirical formulae, expressed as an arbitrary scale from 1 to 20
High HLB => hydrophilic surfactant (o/w emulsifiers)
Low HLB => oil-soluble surfactants (w/o emulsifiers)
55
Optimising microemulsions - 5
1. Homogenous, transparent, low viscosity colloidal systems.
2. Stability requires very low interfacial tension - but the interfacial area is very large.
3. Very low interfacial tension required
4. Implies need for primary & secondary surfactants
5. Careful control of temperature required
56
Viscometer use - 3
1. To produce complete rheograms
2. Capillary & falling spheres used for only newtonian materials
3. Cup & bob, cone & plate are used for both
57
Why are gels solid like - 3
1. Solid-like due to entrapment & adhesion of liquid in the large SA of a solid 3D matrix.
2. Formulation of solid matrix due to cross-linking of polymeric strands of macromolecules
3. At [high] polymer solutions high viscosity shown due to 3D interaction of polymer chains with the solvent.
58
Lotion - 5
1. Thinner, lighter, less greasy than cream
2. Water based
3. Cover large SA of skin
4. Best for general application
5. Absorbs quickly into skin
59
Cream - 5
1. Less greasy than ointments
2. Half oil & half water
3. Cover large SA of skin
4. For daytime use
5. Nourishing ingredients
60
Ointment - 4
1. Greasy & thick
2. 80% Oil, 20% water
3. Good for night-time
