Module Test Flashcards
1
Q
Define solubility
A
The maximum amount of solute that will dissolve in a given quantity of solvent at a given temperature
2
Q
State the three types of solvents
A
- Polar solvents
- Non-polar solvents
- Semi-polar solvents
3
Q
Describe what chemical features on a polar solvent increase solubility
A
- Presence of polar groups
- More branches
- Ratio of polar groups to non-polar groups on molecule
4
Q
Explain the dielectric constant and state whether polar or non-polar solvents have a greater dielectric constant
A
The dielectric constant is the extent to which a material can store electrical charge.
Polar solvents have a higher dielectric constant.
5
Q
Explain hydrogen bonding
A
Interaction between a molecule containing a hydrogen atom and an electro-negative atom on the other molecule
6
Q
Water is a polar solvent that is amphiprotic. Explain what this means.
A
Amphiprotic means that the solvent can act as a proton acceptor or donor.
7
Q
Explain Le Chatteliers principle of equilibrium
A
In an acid + water reaction, adding more acid will cause the equilibrium to shift towards reducing the amount of acid being produced
In an acid + water reaction, adding more base will cause the equilibrium to shift towards increasing the amount of acid produced (as the base reacts with H3O+)
8
Q
State the three types of ‘solutions’
A
- Gas in liquid
- Liquid in liquid
- Solid in liquid
9
Q
Temperature has an effect on the miscibility of liquid-liquid solutions. State and explain the 4 types of ‘critical’ temperatures,
A
- Upper critical temperature (temperature @ full miscibility)
- Lower critical temperature (temperature @ no miscibility)
- Upper & lower critical temperature
- No critical temperature (partial miscibility at all temperatures)
10
Q
State the 4 solvation mechanisms
A
- DIelectric constant
- Dipole formation
- Hydrogen bonding
- Acid-base reaction
11
Q
Define ‘rheology’
A
The study of ‘flow’ and the deformation of matter.
Flow = The tendency of a material to deform following the application of force
12
Q
Discuss the resistance of flow in pharmaceutical applications
A
Water flows readily when poured = low resistance
- Good in certain medication for swallowing/digesting
Honey flows slowly when poured = high resistance
- Good for ointments and gels to stay on skin
13
Q
Explain newtonian flow
A
Shear stress increases in a linear fashion upon increasing shear rate
14
Q
Explain dilatant flow
A
Shear stress increases exponentially upon increasing the shear rate. This is because dilatant fluids are comprised of a high concentration of undissolved fluids. Therefore, when shear displaces the liquid, solid particles clump together and produce more resistance.
15
Q
Explain pseudo-plastic flow
A
Shear stress decreases the shear rate. This is because when pseudoplastic fluids are shaken or stirred, the bonds in the molecules are broken. As a result, viscosity decreases as ‘networks’ are broken.
Pseudoplastic fluids are capable of thixotropy.
16
Q
Explain thixotropy
A
The regain of structural integrity after shearing has stopped. Substances that have experience greater deformity will experience a slower rate of thixotropy.
17
Q
Explain Bingham plastics
A
Bingham plastics act as newtonian fluids (i.e. linear) beyond a certain yield stress. Therefore, before this yield stress, they are fairly solid.
18
Q
State and explain how rheology affect pharmaceutic
A
Formulation stability: more viscous means slower sedimentation of undissolved particles
Biological activity: more viscous means slower movement of drug out of formulation
Patient acceptability: less viscous means easier to pour and swallow
19
Q
Explain viscometry
A
The testing of viscosity. Machine involves immersing a spindle in fluid that can be rotated at different speeds to give a reading of viscosity.
20
Q
Define diffusion and explain its importance to pharmaceutics.
A
The net movement of molecules from a region of high concentration to a region of low concentration.
Important for drug movement and permeation around the body.
21
Q
Diffusion is measured through quantifying molecular flux (f). State the components of molecular flux.
A
Mass (M) over cross sectional area of a barrier (S) and time (t).
Measures how many molecules are travelling through a cross-sectional area per second.
(Note: ‘S’ is the area of the ‘barrier’, NOT the ‘door’ meaning that a bigger barrier will mean a smaller door for the molecules to diffuse through meaning less molecules pass through per second meaning lower ‘f’)
22
Q
Compare and contrast steady state and non-steady state diffusion.
A
Steady state diffusion is when the concentration gradient does not change over time. Non-steady state diffusion is when the concentration gradient changes over time, meaning that molecular flux will also change over time.
23
Q
Describe the distribution of solutes in two immiscible liquids
A
If a solute is added to a mixture of two immiscible liquids, it will distribute itself amongst both phases. The solute will distribute more towards the liquid that is less dense and less polar.
24
Q
State the distribution law and the relevant assumptions made
A
Distribution law: concentration of X in A at equilibrium/concentration of X in B at equilibrium = partition coefficient
Assumptions: temperature remains constant, solute X is below saturation concentration
25
Discuss diffusion (ALL OF IT :L)
- Lipophilicity and passive diffusion
- Lipophilic molecules are better absorbed/diffuse through biological membranes
- At a certain point, increasing lipid solubility will decrease drug activity due to:
- Binding to lipids and only lipids
- Won't migrate towards site of action through fluids
- Functions of biological membrane
- Separate the aqueous contents of the cell from the external aqueous phase
- Allow exchange of materials between inside and outside of a cell
- As a result, biological membranes are lipid in nature, yet have *selective permeability* properties
- Transport across biological membranes
- Cross from one hydrophilic region to another through the lipophilic phospholipid membrane
- Passive diffusion
- Dependent on concentration gradient
- Does not require energy
- Or exploit carriers/aqueous pores in the membrane to get across:
- Facilitated diffusion
- Process involving a specialised carrier
- No energy required
- Dependent on concentration gradient
- Active transport
- Energy is required
- Can go against concentration gradient
- Factors affecting biological diffusion
- Drugs are usually absorbed through passive diffusion
- Which is affected by:
- Lipophilicity of the drug
- Water solubility of drug
- Fraction of unionised form of drug
- Microenvironments of the biological compartments and the membranes involved
26
Compare and contrast LogP and LogD
LogP is the partition coefficient.
LogD is the distribution coefficient.
LogP is the equilibrium ratio of unionized drugs
LogD is the equilibrium ratio of un/ionized drugs
LogP remains constant
LogD changes with pH (fx degree of ionisation)
27
Explain why the pH-partition hypothesis (and hence, LogD) cannot be applied to GI absorption
Variability in pH conditions.
pH at membrane surface is lower than that in the bulk
Convective flow refers to the movement of water into and out of the GI tract, which will affect the absorption rate of small molecules.
28
Explain how ionised molecules can pass through the lipid membrane in the GI tract
The lipid membrane in the GI tract is negatively charged, meaning that it can attract cations (+) near the membrane. As a result, negatively charged molecules can pick up a cation or positively charged molecules can donate their positive charge to the membrane so that they can pass through.
29
Explain the difference between solubility and dissolution
Solubility is the extent to which a solute can dissolve in a solvent.
Dissolution is the rate at which a solute can dissolve in a solvent.
E.g. a drug can fully dissolve (high solubility) at a slow rate (low dissolution)
30
State the 4 classes of drugs in the Biopharmaceutical Classification System
Class 1 - high permeability, high solubility
Class 2 - high permeability, low solubility
Class 3 - low permeability, high solubility
Class 4 - low permeability, low solubility
31
State the properties required of a formulation to be eligible for a biowaiver and which class of drug is most likely to be eligible.
Rapid dissolution
High solubility
High permeability
Wide therapeutic window
Class I drugs.
32
Explain what is meant by 'sink conditions'
'Sink condition' is when the concentration of a drug/solute in the receptor region is significantly lower than in the donor region.
33
Explain why solute concentration in receptor region is not considered in the equation, J = DKC(d)/h
```
J = molecular flux
D = diffusion coefficient
K = partition coefficient
Cd = solute concentration in donor region
h = thickness of membrane
```
Because under 'sink conditions', ideally, the lowest possible solute concentration in the receptor region is approximately zero, meaning that it is negligible.
34
Explain the difference between steady-state and non-steady-state diffusion
Steady-state diffusion follows Fick's first law and assumes that the concentration gradient remains constant over time. Therefore, the rate of diffusion is dependent on the concentration gradient.
Non-steady-state diffusion follows Fick's second law and states that the rate of diffusion is proportional to the rate of change of the concentration gradient.
35
Describe what a biowaiver is and the properties that a formulation must possess to be eligible for a biowaiver.
A biowaiver is an exemption from conducting human bioequivalence studies.
Properties:
- Rapid and similar dissolution
- High solubility
- High permeability
- Wide therapeutic window
- FDA approved "immediate release" excipients
36
What is meant by a 'dispersed system'? (provide 2 examples)
A system containing a dispersed phase (internal phase) and a continuous phase (dispersion medium).
Suspension - solid in liquid dispersion
Emulsion - liquid in liquid (immiscible) dispersion
37
State the 3 classes of dispersion. Compare and contrast their properties.
- Molecular (diffuses fast, invisible under an electron microscope, passes through ultrafilter)
- Colloidal (diffuses slowly, visible under electron microscope but not light microscope)
- Coarse (does not diffuse, visible under light microscope, does not pass through normal filter)
38
A suspension is a coarse dispersion in which insoluble particles are dispersed in a liquid medium. Explain the applications of a suspension in terms of routes of administrations.
Oral route - can deliver water-insoluble drugs in an aqueous vehicle, taste masking, reduce hydrolysis
Topical route - slow drug release due to formulation needing to dissolve to produce an effect
Parenteral route - administer through IM or SC but not IV (due to risk of blocking vessels)
39
Describe the disadvantages of suspensions
- Sedimentation (caking)
- Dose precision
- Microbial contamination
- Bulky packaging (bottles)
40
Describe the changes you can make to the formulation of a suspension to increase or prolong the rate of drug release.
Increase - in order to increase the rate of dissolution which results in high initial concentrations, the active component can be converted to a salt.
Prolong - to decrease the rate of dissolution and therefore have a prolonged release, the active component can be converted to a polymorph.
41
Describe the effect of wetting agents on suspensions
The high interfacial tension between the solid water-insoluble drug and the liquid medium may cause the solid drug molecules to clump up and aggregate in order to reduce the surface area exposed to the liquid.
Adding a wetting agent that decreases interfacial tension will prevent the drug molecules from aggregating
42
In terms of particle size control, Stoke's law states that the force required to move a sphere through a given viscous fluid is proportional to the velocity and radius of the sphere. State a limitation of this law.
Stoke's law does not apply when there is an excessive amount of the suspended material due to collisions that influence the velocity.
43
State 3 advantages and 1 disadvantage of a smaller particle size
+ Slower rate of sedimentation
+ Less mechanical irritation
+ Ease of administration (no blocking of injection needle)
- Does not allow slow drug release
44
Viscosity modifiers can be used to alter the physical properties of suspensions. State 4 physical properties of a well-formulated suspension.
- Slow sedimentation
- Easy re-dispersion
- Homogenous
- Easily transferable
45
Explain the ideal rheological properties in terms of standing, shaking and leaving with reference to viscosity
Standing - High apparent viscosity at low rates of shear so that on storage the suspended particles would either settle very slowly or preferably remain permanently suspended
Shaking - At moderate shear rates, the apparent viscosity should fall sufficiently to allow the suspension to be easily poured
Leaving - Original apparent viscosity should be regained after a relatively short time to maintain adequate levels of physical stability
46
Provide examples of viscosity modifiers
- Polysaccharides
- Acacia
- Tragacath
- Alginates
- Starch
- Xantham gum
- Water-soluble celluloses
- Methylcellulose
- Hydroxy methylcellulose
- Hydrated silicates
- Bentonite
- Magnesium aluminium silicate
- Hectorite
- Carbomers
- Carboxy polymethylene
- Colloidal silicon dioxide
- Aerosil
47
Explain the difference between flocculated and deflocculated systems
Flocculated - loose sediments held together by weak van der Waals forces with a small amount of liquid medium in between, easily re-dispersible and fast sedimentation which can lead to inaccurate dosing
Deflocculated - a slower rate of sedimentation, therefore, more uniform dosing but prone to caking
48
Explain why flocculated particles sediment faster
Flocculated particles are particles that are loosely connected together. As a result, due to Stoke's law, the particles are now 'bigger' which means that the velocity at which they sediment increases.
49
Discuss how flocculation can be controlled using electrostatic stabilisation
Electrostatic stabilisation refers to the electrostatic charge of the particle surface and its ability to attract oppositely charged ions. Since particles of the same charge exert repulsive forces on each other, the attraction of these ions (and hence, the neutralisation of the particle) means that these repulsive forces are reduced. As a result, the particles are able to flocculate.
Electrolytes can be used to add ions to the suspension.
50
Define 'zeta potential'
Zeta potential is the potential difference between the dispersion medium and the stationary layer of fluid attached to the dispersed particle.
51
Define an emulsion and state the two types
Two-phase systems in which one phase is dispersed as fine droplets into another phase.
Coarse emulsions and microemulsions.
52
Explain the pharmaceutical relevance of emulsions
Emulsions allow us to entrap oil soluble drugs in dissolved form within an aqueous system and vice-versa.
Additionally, by designing a formulation that requires a drug to partition through different phases to reach its target, we can achieve sustained release.
53
Explain why an emulsion may be appropriate for oral and topical route formulations
Oral route - easy to swallow (oily drug in aqueous medium), allows for taste masking
Topical route - can be made more viscous (ointments), pseudo-plastic properties for ease of administration
54
Describe the role of an emulsifier and provide examples
Emulsifiers coat the dispersed phase droplets to reduce the interfacial tension between the droplets with the medium.
Examples:
- Surfactants
- High molecular weight alcohols
- Protein substances
55
State and explain 4 processes that must be avoided for an emulsion to be stable with reference to reversibility and irreversibility.
Flocculation - droplets loosely aggregate into loose clusters (reversible with shaking)
Creaming - higher concentration of drug in one region leads to lack of uniformity in distribution (reversible with shaking)
Coalescence - dispersed droplets flow together to gain energy, surfactant layer in the interface is broken down (irreversible with shaking)
Breaking - phase separation (irreversible with shaking)
56
Explain how flocculation can be reduced in emulsions
- Adding charged emulsifiers (cationic surfactant) but can be toxic
- Adding electrolytes to reduce charge
57
Explain how creaming can be reduced in emulsions
- Reduce droplet size
- Increase viscosity
- Reduce density difference between 2 phases
58
Explain how coalescence can be reduced in emulsions
- Reduce interfacial tension by adding surfactant
- Add mechanical barrier by adding hydrocolloid
- Increase droplet charge to induce repulsion
59
Explain why microemulsions are more efficient than emulsions using Neoral and Sandimmune as examples.
Sandimmune is an o/w emulsion that requires further emulsification by bile salts and digestion by pancreatic enzymes prior to absorption.
Neoral is a preconcentrate that forms a homogenous microemulsion immediately on contact with GI fluids (i.e. less dependent on bile salts for absorption).
Neoral has a more consistent PK behaviour, less inter and intrapatient variation, and a more consistent bioavailability when administered with food.
60
Define 'dosage form' and provide a reason why biologically active entities are not usually administered as pure chemical substances.
Dosage forms are clinical packages in which a drug is presented to a patient.
Before biologically active entities are administered, we must consider patient acceptability, therapeutic issues, toxicity, stability, etc. As a result, we instead administer formulate preparations.
61
State the criteria that are considered when making a drug
- Stability
- Reliability
- Convenience
- Palatability
- Effectiveness
62
Explain excipients
Chemical substances that aid in the formulation of a drug into the desired dosage form. Excipients are inner and physically and chemically stable.
Numerous functions include to solubilize, flavour, preserve, emulsify, suspend, etc.
63
Explain the Pulsincap release
The Pulsincap delivery system is a time-dependent release formulation comprised of:
- Enteric coat
- Capsule cap
- Hydrogel plus
- Drug wafer
- Ghost capsule body
64
Define bioavailability
The relative amount of an administered dose of a drug that reaches the systemic circulation unchanged.
The difference in bioavailability can vary with different routes of administrations, dosage forms or formulations.
65
Define bioequivalence
The comparison of the bioavailability of a drug to a recognised standard dosage form. BE determines if the rate and extent of absorption are equivalent in test and standard drug.
66
Explain how particle size affects the effectiveness of a drug
Smaller particles have a greater surface area. As a result, they have increased contact with the dissolution medium and will dissolve faster, leading to greater absorption.
67
Explain the Noyes-Whitney's equation
dm/dt=kA(Cs-C)
```
dm/dt = the dissolution rate
k = dissolution rate constant
A = surface area of drug
Cs = solubility of the drug
C = concentration of solute in bulk solution at a time
```
68
Explain the common ion effect in relation to solubility
The common ion effect is the phenomenon whereby the addition of a common ion significantly reduces the solubility of a slightly soluble electrolyte (drug).
This is because when the common ion is added (e.g. by dissolving a salt), there is an increase in 'products' which causes the equilibrium to shift back towards the reactant (drug). It is important to note that this can only occur in slightly soluble systems due to the presence of an equilibrium.
69
What is the rate-limiting step in the absorption process of poorly soluble drugs vs. freely soluble drugs
The rate-limiting step in poorly soluble drugs is disintegration. In freely soluble drugs, permeability is the rate-limiting step.
70
Drugs can decompose as a result of heat, light, oxygen, moisture and pH changes. State the 4 classifications of drug stability.
1. ) Stable under all conditions
2. ) Stable if handled correctly
3. ) Moderately stable even with special handling
4. ) Very unstable
71
State the advantages of oral route drug administration
- Simple
- Convenient
- Safe
- Local and systemic effects
72
State the disadvantage of oral route drug administration
- Must survive acidic conditions to be absorbed by GIT
- Slow onset of action
- Irregular absorption with food
73
Briefly outline the anatomy of the GI tract
Oesophagus - links mouth and stomach, movement through swallowing
Stomach - temporary reservoir to deliver to the intestine, gastric secretions
Small intestine - capable of digestion and absorption, villi, duodenum, jejunum, ileum
Large intestine
74
Define peptide drugs and protein drugs
Peptide drugs are drugs that have less than 50 amino acids
Protein drugs are drugs that have more than 50 amino acids
75
Define transcellular and paracellular transport
Transcellular - across cells
Paracellular - between cells (particularly in the small intestine due to being 'leaky')
76
Briefly describe the buccal route of drug administration
Drug administration through dissolution and diffusion in the oral cavity.
Treats local and systemic conditions and suitable for large, hydrophilic and unstable drugs.
77
State the advantages of the buccal route of administration
- Avoids the first-pass effect
- Ease of administration and termination
- Sustained release
- Drug in a less hostile environment than GIT
78
State the disadvantages of the buccal route of administration
- Small absorption surface area (compared to GIT)
- Oral cavity movement affects mucoadhesives
- Less permeable (than small intestine)
- Salivation and swallowing
- Palatability needs to be considered
79
State the advantages of the nasal route of administration
- Avoids the first-pass effect
- Rapid absorption
- Low enzymatic levels mean easy saturation of drug
80
State the disadvantages of the nasal route of administration
- Low dose
- Nasal irritation
- Offensive odours
- No toxic nasal metabolites
81
State the advantages of the intravenous route of administration
- Immediate access to the bloodstream
- Maximum concentration reached rapidly
- Large and small volumes can be given
- Duration depends on the dose, ADME and the timescale of administration (single bolus vs. constant infusion)
82
Explain the rate-limiting step of the intramuscular route of drug administration
IM is dependent on molecules being able to diffuse through the pores of capillary walls. Hence, transport through these capillary walls is the rate-limiting step
83
Provide a reason why subcutaneous injection occurs slower than intramuscular injection
Dissolution and absorption occur slower in SC because the blood supply is not as good as it is in IM
84
Briefly describe intrathecal drug administration
A method of delivering drugs to the brain and spinal cord via injection into the spinal canal.
Generally more 'invasive' than IV, IM and SC.
85
Rectal drug delivery can often be used in place of PO. Provide advantages and disadvantages of rectal drug delivery.
+ Avoids the first-pass effect
+ Local and systemic
- Slow and incomplete absorption
- Significant inter/intra-subject variation
86
Describe how rectal drug delivery occurs
Suppository dissolves in rectal fluid or melts on the mucous layer (depending on vehicle). Drug molecules will then enter general circulation (avoid first-pass) or via the liver.
87
Briefly discuss vaginal drug delivery
Generally used for local effects but the wide network of blood vessels in the vagina can allow for systemic effects. Drug adheres to mucosal layer in vagina and dissolves. Absorption tends to vary.
88
State the advantages of pulmonary drug delivery
- Direct administration to site of action (lungs)
| - Rapid onset of action
89
State the disadvantages of pulmonary drug delivery
- Seeks to defeat the body's natural defences
- Demanding on patient
- Patient variability
- Specific particle size necessary for the absorption
90
Recommend methods of masking the taste of orally administrated drugs
- Coating tablets
- Using capsules
- Making emulsions/suspensions
91
Define preformulation
A branch of pharmaceutical science that utilizes biopharmaceutical principles in the determination of physicochemical properties of drug properties
92
Describe why preformulation is significant to drug delivery and formulation development
Drug delivery - new chemical entities (NCE) should possess optical biopharmaceutical properties to become drugs.
Formulation development - physicochemical properties must be studied, dictates possible approaches to formulation development and helps understand events and mechanisms of a drug at different stages.
93
Describe the importance of the analytical method of fundamental preformulation parameters
To determine the amount of the compound of interest is present since impurities can be present too. This is done by UV-Vis and HPLC.
94
Describe intrinsic solubility
Refers to the solubility of the drug in an unionised form. Drugs in unionised form are more lipophilic and easily absorbed.
95
Explain LogP and how we can distinguish lipophilicity and hydrophilicity with the LogP value
Measure of the relative solubility of drug in solvents compared with its solubility in water.
LogP > 1 - Lipophilic
LogP < 1 - Hydrophilic
96
Explain polymorphism
Polymorphs relates to solid material with at least two different molecular arrangements which give distinct crystal species
Polymorphs markedly differ in their physical, chemical and optical properties due to different crystalline structures
Highest melting species are usually most stable (form 1), others (form 2, 3, etc.) are metastable and have a tendency to convert to the stable form
97
State the 7 Fundamental Preformulation Parameters
- Analytical method
- Solubility
- Salts
- Partition Coefficient
- Melting Point
- Polymorphism
- Stability
98
State the 4 Derived Preformulation Parameters
- Microscopy
- Particle size analysis
- Bulk density
- Flow properties
- Excipient compatibility
99
Explain why particle size analysis is important
Particle size can influence dissolution rate, uniform distribution, penetrability and suspendability.
100
State 5 methods of particle size determination
- Sieving
- Optical microscope
- Sedimentation
- Coulter counter
- Laser diffraction
101
Explain Differential Scanning Calorimetry
DSC is a method of measuring excipient compatibility.
Comprises of comparing the DSC interactions between a sample of the drug and a sample of a 50:50 drug-excipient mixture.
Interaction example: melting point.
102
Define bioavailability
Extent and rate at which a substance or its active moiety is delivered from a pharmaceutical form and becomes available in the general circulation.
103
Compare and contrast absolute BA and relative BA
Absolute - comparison of the bioavailability of a particular dosage form with that following IV administration (100%).
F = (AUCev/AUCiv) x (DoseIV/DoseEV)
Relative - comparison of AUC value of different dosage forms.
F = (AUCev1/AUCev1) x (DoseEV2/DoseEV1)
104
State and explain the two parameters of measuring BA
Extent of absorption - the fraction of the dose which enters systemic circulation
Rate of absorption - the time delay between the administration of the drug and the time of maximum concentration in the plasma.
105
State factors that affect BA and provide methods to avoid variation when testing for BA
Factors:
- Body weight
- Sex and age
- Disease
- Genetics
How to avoid:
- Choose subjects with similar ranges
- Specify ranges to maintain consistency
106
Compare and contrast brand-name drugs and generic drugs
Brand-name drug:
- Supplied by one drug company
- Sold under drug company's trademarked name
Generic drug
- May be supplied by more than one company
- May be sold under different names
- Lower cost version of the brand name drug
107
Explain patent protection
Patent protection protects the investment of the drug company that developed the drug by giving sole rights to that company to sell that drug while the patent is in effect.
108
Define pharmaceutical equivalence
Drugs are considered pharmaceutical equivalents if they contain the same active ingredients, the same dosage form, route of administration and are identical in strength and concentration.
But they may differ in characteristics such as shape, scoring configuration, release mechanisms, packaging, excipients (inc. colours, flavours, preservatives) and, within certain limits, labelling
109
Define therapeutic equivalence
Drug products are considered to be therapeutic equivalents only if they are pharmaceuticals equivalents and if they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labelling
110
Define pharmaceutical alternatives
Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety, but are different salts, esters, or complexes of that moiety or are different dosage forms
111
Define bioequivalence
The absence of significance difference in the rate and extent to which an active ingredient or active moiety in pharmaceutical equivalence or pharmaceutical alternative becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.
112
Describe how two products can be considered interchangeable
When they are pharmaceutically equivalent.
When their BA after administration in the same dose are similar to a degree where efficacy and safety are the same.
113
State the attributes that make two products non-interchangeable
- Product has a narrow therapeutic index
- Product delivery systems are not pharmaceutically equivalent
- No acceptable method to establish BE (e.g. topical products - since every individual's skin is different and will respond differently)
114
State the 3 properties of small particles
- Particle size
- Particle shape
- Particle surface area
115
Describe what is meant by a 'hypothetical sphere'
In order to measure the diameters of irregular (non-spherical) particles, we approximate a 'hypothetical sphere' for such particles. This ensures that we can as accurately as possible measure its size. Hypothetical spheres can be determined using length, weight, volume, surface area, etc.
116
Explain the difference between Martin's diameter and Feret's diameter
Martin's diameter -distance between opposite sides of a particle on a line bisecting the projected area.
Feret's diameter - distance between parallel tangents on opposite sides of the particle profile.
117
Define the projected area diameter
The diameter of a circle with the same area as that of the particle.
118
Define the projected perimeter diameter
The diameter of a circle having the same perimeter of the particle.
119
State the disadvantages of microscopy
- Only 2-D
- Tedious
- Eye strain
- Operator error
120
State the 6 methods of determining particle size
- Microscopy
- Sieving
- Coulter counter
- Laser light scattering
- Photon correlation spectroscopy
- Sedimentation
121
Explain sieving
Sieving is a method of determining particle size by having particles pass through multiple sieves of different diameters.
The particles ability to pass through depending on size, orientation and shape.
122
State the disadvantages of sieving
- Small amount of sample
| - Difficulty sieving oily or cohesive powders/granules due to clogging
123
Explain the Coulter Counter method of particle size determination
The powdered substance is dispersed in electrolyte liquid. Particles passes between two electrodes which monitor the change in electrical signal when the particle occupies orifice and displaces a volume of electrolytes equal to its own.
Change in resistance is proportional to volume. Resistance is converted into a voltage pulse which is amplified and processed electronically.
124
State the practical considerations when using the Coulter Counter method
- Tube selection
- Electrolyte (must conduct electricity but not dissolve particles)
- Dispersion (need suitable concentration, break aggregates, representative sample)
- Coincidence (changes of more than one particle at a time < 10%)
125
State the two types of light scattering techniques used for particle size determination and determine under what conditions would you use one over the other.
- Laser diffraction (particle diameter 1-1000 um)
| - Photon correlation spectroscopy (particle diameter 0.001-1 um)
126
Explain the lase diffraction method of particle size determination
Observes the interaction between particles and the wavelength of light. Larger sized particles diffract light in irregular patterns to a lesser degree. Smaller sized particles diffract light in irregular patterns to a greater degree.
127
State and explain the two theories that laser diffraction is based on
Fraunhofer theory - light interactions with particles causes light to be scattered in a forward direction with only a small change in angle.
Mie scatter theory - agrees with Fraunhofer, but also accounts for some side scatter of light. Therefore, considers optical properties of particles (i.e. refractive index)
128
Explain the Photo Correlation Spectroscopy method of particle size determination
Based on the Brownian motion (random movement of particles due to collision), PCS analyses the constantly changing patters of laser light scattered or diffracted by particles that produce a flicker. The smaller the particle, the higher the rate of flicker.
129
Explain the Sedimentation method of particle size determination
Measurement of particle size through observing particle's free falling velocity.
Follows Stoke's law which assumes smooth, rigid sphere, no particle interactions and aggregation.
130
Define porosity and state the associated equation
Porosity is the measure of void spaces in materials.
(Vb-Vp)/Vb
```
Vb = bulk volume
Vp = true volume
```
131
State the 6 derived properties of powders
- Porosity
- Packing arrangements
- Density
- Flow properties
- Dissolution
- Compaction
132
State the two ideal packing arrangements
- Rhombohedral (3 particles)
| - Cubic (4 particles)
133
State the three types of densities
- True density (excluding all voids)
- Granule density (determine by mercury displacement
- Bulk density (determine by bulk volume and weight)
134
Explain the significance of flow properties
Powders need to flow well for a uniform distribution, and consistent drug amounts in each tablet.
135
Describe the method used to measure flow properties
Angle of repose - the maximum angle that can be obtained between the free-standing surface of a powder heal and the horizontal plane.
Based on the particles cohesive vs. adhesive properties.
Greater angles of repose indicate poor flow.
136
Describe the factors influencing flow properties
Particle size - fine particles with high surface area are more cohesive
Particle size distribution - reducing fine particles and increasing large particles (granulation)
Particle shape and texture - spherical particles have better flow
Moisture content - moisture impairs flowability, powders should be dried
137
Define compactibility
A powders tendency/ability to form a coherent tablet. Powders with high compatibility can form tablets with high resistance against capping and lamination.
Granules have better compactibility than powders.
138
State 5 methods of stabilising an emulsion
- Change particle size
- Change viscosity
- Introduce a surfactant
- Introduce a mechanical barrier
- Increase charge
139
State 5 factors affecting dissolution rate
- DIffusion coefficient of the solution (viscosity, temperature, solvent)
- Surface area of solid
- Solubility of solid
- Concentration of solute in the bulk
- Thickness of diffusion layer
140
Define a solution
A homogenous mixture of two or more components.
141
State and define the two types of solutions
Non-electrolyte - substances that do not ionise in water
Electrolyte - substances that ionise in water (strong electrolytes completely ionise in water, weak electrolytes incompletely ionise in water)
142
State the conditions of an ideal solution
- No change in properties of the components other than dilution
- No heat is evolved or absorbed during the mixing process
- No expansion or shrinkage
Non-ideal solutions are solutions where the mixing of components is associated with the evolution of heat or some other change (other than dilution)
143
Under what conditions would you expect positive and negative deviations from Raoult's law?
Adhesive < Cohesive = vapour pressure is greater than expected from Raoult's law
Adhesive > Cohesive = vapour pressure is less than expected from Raoult's law
144
State the 4 colligative properties
- Lowering vapour pressure
- Boiling point elevation
- Freezing point depression
- Increasing osmotic pressure
145
State advantages and disadvantages of solutions
+ Easy to swallow
+ Homogenous mixture
+ Flexible dosing
+ Various RoA
- Bulky packaging
- Low shelf-life
- Microbial growth
146
Define complexes
Compounds result from Lewis acid-base reactions between two or more chemical constituents results in a covalent bond - sharing of electrons.
Complexes are composed of two. or more molecules or ions held together in a unique structural relationship.
147
State the 3 types of complexes
- Inclusion complex
- Metal ion complex
- Organic molecular complex
148
Inclusion complexes involve a constituent being trapped in a cage-like crystal structure of the other. State the 4 types of inclusion complexes.
- Channel lattice type
- Layer type
- Clathrates
- Cyclodextrin inclusion
149
Explain the channel lattice type of inclusion complexes
Inclusion complexes whereby compounds crystallize in a channel-like structure permitting enclosure of non-branched compounds.
Example: urea
150
Explain the layer type of inclusion complexes
Inclusion complex whereby compounds are trapped in clay minerals.
151
Explain the channel lattice type of inclusion complexes
Inclusion complexes whereby compounds crystallise in the form of cage-like lattices in which guest molecules can be trapped.
Dependent on the molecular size of the guest molecule.
152
Explain the monomolecular type of inclusion complexes
Monomolecular complexes involve the entrapment of a single guest molecule in the cavity of a host molecule.
Example: cyclodextrin
153
Explain the structure of cyclodextrins
Cyclodextrins are cylindrical rings with a large interior cavity that can hold guest molecules. The inner layer (cavity) is hydrophobic whereas the outer layer is hydrophilic. This allows the complex to hold hydrophobic guest molecules of the appropriate size.
Example: Piroxicam, mitomycin C
154
State the applications of cyclodextrin
- Solubility enhancement
- Taste masking
- Stabilizer and protector
- Dissolution enhancement
155
Explain metal ion complexes
Type of inclusion complex whereby ligands donate a pair of electrons to metal ions (acceptors) forming a complex.
156
Explain chelates, a subtype of metal ion complexes
An organic substance containing two or more donor groups combining with metal to form a special complex.
157
State the applications of chelates
- Heavy metal detoxification
- Drug stabilisation
- Pharmaceutical assays
158
State the two types of organic molecular complexes
Polymer complex - modify biopharmaceutical parameters of the drug (e.g. reduce staining and irritation)
Drug complex - improves drug release and absorption
159
Explain the Basket Assembly dissolution apparatus
Tablet is placed in a rotating basket within a vessel and samples of the liquid it is immersed in are taken at different time intervals to measure dissolution.
160
Explain the Paddle method dissolution apparatus
Tablet is placed at the bottom of a vessel below a rotating paddle. Likewise, with the Basket Assembly method, a sample of the liquid within the vessel is taken at different time intervals to measure the level of dissolution.
161
State 4 techniques used to modify drug release
- Enteric coating
- Matrix
- Bioadhesive
- Ion-exchange resins
162
Explain enteric coating in terms of modified drug release
- Can protect the drug from harsh gastric environment
- Can protect stomach lining from irritation from drug
- Can allow drug to dissolve at certain regions of the GIT
163
Explain bioadhesive polymers in terms of modified drug release
The coating on the delivery system binds to biological surfaces (mucoadhesion). This allows for increased contact time with the target tissue for sustained release.
164
Explain polymer matrices in terms of modified drug release
The process involves fluid penetrating matrix and reaching drug, fluid dissolving drug and the drug leeching out. These steps allow for prolonged release.
165
State and explain the two types of polymer matrices
Non-erodible - drugs molecules near the surface of the matrix are dissolved first meaning high initial concentration. However, since non-erodible matrix, fluid is required to travel deeper to reach drug molecules near the centre of the formulation. As a result, prolonged release and inconsistent concentration.
Erodible - fluid dissolves drug molecules and polymer matrix meaning that drug molecules near the centre become more exposed.
166
Explain the concept of an osmotic pump
Osmotic pumps involve the drug, a semi-permeable membrane, osmogens and a delivery orifice.
The semi-permeable membrane allows water to enter and come into contact with the osmogen. This causes the osmogen to expand and 'push out' the drug through the delivery orifice. The orifice is the only way the drug can be released which allows for a controlled release.
167
Explain ion-exchange resins
Ion-exchange resins are used for cationic and anionic drugs whereby a resin bead is attached to a drug to neutralise it. The drug is released when it comes into contact with biological fluid where it will detach from the resin.
168
State the assumptions made by the Higuchi equation
- Initial drug concentration in the matrix is higher than drug solubility
- Diffusion takes place in one dimension
- Matrix does not erode
- Drug diffusion is constant
- Perfect sink conditions
169
Describe the differences in the appearance of a Fickian line vs. a Case II line in the Korsmeyer-Peppas graph and explain what they mean
Fickian - line is slightly curved indicating that there is an initial high concentration which eventually slows down. This shows that a non-erodible matrix is used as the presence of a depletion zone reduced the rate at which the drug molecules at the centre reach the fluid and dissolve.
Super Case II - linear drug release over time showing an erodible matrix that lacks a depletion zone, therefore, drug molecules both near the surface and at the centre are exposed to the fluid at an equal rate as the tablet degrades.
