Pharmaceutics Flashcards
What is rheology?
The science of flow. Describes the flow of liquids and deformation of solids.
Two underlying concepts of rheology?
1) Intermolecular forces and bonding
2) timetable of experimental observations
What is viscosity?
An expression of the resistance of a fluid to flow
What did Hooke define?
an ideal elastic solid
What did Newton define?
An ideal liquid
What does viscoelastic mean?
Having both liquid and solid character
Newton’s law of flow states?
The rate of flow is directly proportional to the applied stress
What is shearing stress?
The force per unit area to bring about flow
What is a Newtonian fluid?
Viscosity does not chance with increased shear rate, only with temperature
How to tell a Newtonian fluid on a graph?
proportional and linear
What is viscosity measured in?
poise or Pas
What is the Mark-Houwink equation for?
Determining molecular weight from viscosity
Types of non-newtonian fluids?
Shear-thinning (pseudoplastic)
Shear-thickening (dilatant)
Bingham (plastic)
Emulsion definition?
An emulsion is a thermodynamically unstable mixture of two immiscible liquids. One of the liquids is dispersed as globules inside the other. They are stabilised by an emulsifying agent.
What types of emulsions are there?
Oil-in-water
Water-in-oil
Double emulsions
What is the most common type of emulsion?
Oil-in-water
What are oil-in-water emulsions used for?
Oral
Injectable
Ophthalmic
Topical
Oil-in-water emulsions require what kind of emulsifying agent?
Hydrophilic
Examples of hydrophilic emulsifying agents?
Sodium lauryl sulfate
Triethanolamine sterate
Sodium oleate
Glyceryl monostearate
What are water-in-oil emulsions used for?
Mainly topical application
Water-in-oil emulsions require what kind of emulsifying agent?
Lipophilic
Examples of lipophilic emulsifying agents?
Calcium palmitate
Sorbitan esters
Cholesterol
Wool fats
How to identify the phases of an emulsion?
1) Add a small quantity of water-soluble dye (e.g. Methylene blue) to the surface. If dissolves uniformly throughout it is an oil-in-water, if the dye lies in clumps on the surface it is water-in-oil
2) Dilute emulsion with water. If it mixes freely it is an oil-in-water
3) Apply current to emulsion via electrodes. If current carried across it is oil-in-water
Why do two immiscible liquids not mix?
They have higher cohesive forces than adhesive forces.
O and H in water bond with surrounding water molecules through dipolar and hydrogen bonds.
C in oil bond with surrounding molecules through weak hydrophobic and Van der Waals forces
What are the three emulsion theories?
Surface tension theory
Interfacial film theory
Monomolecular adsorption/ orientated-wedge theory
What is surface tension theory?
1) to form an emulsion the phases need to interact and overcome interfacial tension
2) when one phase is broken into small globules the interfacial area is much greater than the minimum surface area of that liquid in a phase separated system
3) adding an emulsifying agent lowers interfacial tension by adsorbing to the interface on the globule, allowing phases to interact
What is interfacial film theory?
An emulsifier located at the interface between oil and water phases forming a thin film by being adsorbed onto the surface of dispersed globules
Film needs to be rigid enough to establish the interface but flexible enough that collision of globules does not rupture film
The main difference between surface tension theory and interfacial film theory?
In surface tension theory the emulsifier absorbs to the globule in separate ‘bridges’, whereas in interfacial film theory the emulsifier creates a film all around
What is orientated-wedge theory?
Assumes formation of a monomolecular layer of emulsifier around the globule
Emulsifiers orientate themselves around the globule according to their solubility.
Emulsifiers are amphiphilic.
Prevent coalescence when globules become too close to each other
Why are there different emulsification theories?
Because of the different types of emulsifiers
What are the three main groups of emulsifiers?
Surface active agents (surfactants)
Hydrophilic colloids
Finely divided solid particles
How do surfactant emulsifiers work?
Adsorbed at the oil-water interface to form a monomolecular film and reduce interfacial tension
How do hydrophilic colloids work as emulsifiers?
Form a multimolecular film around the dispersed globules of an oil-in-water emulsion
How do finely divided solid particles work as emulsifiers?
Adsorbed around dispersed globules
What is the most common type of emulsifiers?
Surfactants
What does surfactant stand for?
Surface-active agents
What is a key property that determines the type of an emulsifier?
Hydrophilic-lipophilic balance (HLB) value
What HLB value is needed for an oil-in-water emulsifier?
9-12
What HLB value is needed for a water-in-oil emulsifier?
3-6
What is the Bancroft rule?
The phase in which an emulsifier is more soluble constitutes the continuous phase
How are emulsions made?
1) homogenised (mixed)
2) Two phases assembled separately and then combined by slowly adding the dispersion phase to the continuous phase with constant mixing
3) If an oil-in-water emulsion has more than one emulsifier then the higher HLB value should be added first
4) Volatile(flavours) and thermosensitive ingredients added after emulsion formed
5) APIs can be pre-dissolved in one of the phases or added at the end depending on the drugs solubility, stability and partitioning properties
What can go wrong with emulsions?
Stability issues
Chemical instabilities
Microbial issues
What is creaming?
The upward movement of less dense dispersed oil globules in an oil-in-water emulsion.
Visually evident with separation of layers.
Reversible by shaking
What is sedimentation?
The downward movement of more dense dispersed water globules in a water-in-oil emulsion.
Visually evident with separation of layers.
Reversible by shaking
What is the difference between creaming and sedimentation?
Creaming occurs in oil-in-water emulsions whereas sedimentation occurs in water-in-oil emulsions
What is Stoke’s law?
models creaming and sedimentation in an emulsion. Can be used to enhance physical stability of emulsions
How to enhance the stability of an emulsion?
Decrease globule size to <5micrometers
Increase viscosity of the system, such as adding hydrophilic polymers to the continuous phase if oil-in-water emulsions
Decreasing interfacial tensions, such as adding hydrophilic polymers to the continuous phase if oil-in-water emulsions
Reduce the density differences between the two phases
What is aggregation/flocculation?
It involves the close packing of the dispersed phase, but the globules do not fuse.
It is reversible to an extent.
What is coalescence?
When emulsified globules merge to form large particles.
Irreversible as film around globule is destroyed.
Leads to progressive increase in size of the dispersed phase leading to breaking.
What is breaking?
Complete separation of the two liquid phases.
Irreversible as emulsifying films have been destroyed.
What is a semi-solid dosage form?
A body of product which when applied to the skin or other mucous membrane, alleviates or treats a pathological condition or other protection against a harmful environment
Ideal physical properties of a semi-solid dosage form?
Smooth texture Elegant appearance Non-dehydrating Non-gritty Non-greasy Non-staining Non-hygroscopic (doesn't absorb moisture from the air)
Ideal physiological properties of a semi-solid dosage form?
Non-irritating
Doesn’t alter membrane function
Miscible with skin secretions
Ideal application properties of a semi-solid dosage form?
Easily applicable with efficient drug release
High aqueous washability
Ointment definition?
Homogenous, translucent, viscous semi-solid preparations for topical use. Can be medicated or non-medicated
Types of bases?
Oleaginous
Absorption
Water-removable
Water-soluble
How can ointments be prepared?
Incorporation
Fusion
Compendial requirements for ointments?
Microbial content
Minimum fill
Packaging, storage and labelling
Additional standards
Creams definition?
Viscous, semi-solid emulsion with an opaque appearance as contrasted with translucent ointments. Can be water in oil or oil in water
What does cream consistency depend on?
Where it is water in oil or oil in water
What type of emulsifying agent does a water in oil cream contain?
Lipophilic
What type of emulsifying agent does a oil in water cream contain?
Oil in water
Main use of water in oil creams?
Emollient or cleansing agent
Main use of oil in water creams?
Elegant drug delivery systems
Features of pastes?
Contain a high percentage (>50%) of insoluble solid
How are pastes prepared?
Incorporating solids directly into a congealed system by levigation with a portion of base to form a paste-like mass
Advantages of pastes?
Good adhesion on skin
Less greasy