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Pharmaceutical sciences exam 3
Terms in this set (182)
a mixture of one phase in another
(not homogenous mixture) phase
Solid particles (insoluble) dispered in a liquid medium
Liquid droplets (Immiscible ) dispersed in a liquid medium
homogenous and form true solutions (Invisible under electron microscope)
Molecular dispersion pass through
ultrafilter and semipermeable membrane
Colloidal dispersion pass through
through semipermeable membrane
do not pass through notmal filter paper or dialyze through semipermeable membrane (particle visible under microscope)
Advantages of Pharmaceutical Solutions
easier to swallow, allows convenient delivery of drugs to skin/mucosal membrane, allows preparation of parenteral formulations for insoluble drugs, and taste masking
Disadvantages of Pharmaceutical suspension
risk of physical instability, bulkier product, and drug may be more stable than in a solution
Drug substance should be uniformly dispersed after shaking the container till the dose is withdrawn
Any settled/sedimented solid phase should e readily uniformly dispersable upon manual shaking of the container
Desirable physical properties of pharmaceutical suspensions
Suspendable, re-dispersabe, transferable, and smooth/grit-free
Physical stability of suspensions generally refers to
the state of no aggregation and uniform distribution of particles
Preperation of dispered systems involves _________? the particle size of the
Decreasing hte particle size of hte dispered phase results in an increase of its ?
surface area, and thus its interfacial area which results in an increase surface free energy and a system that's thermodynamically unstable
Interfacial tension arises from the imbalance in the
attractive forces for molecules on the solid surface vs. molecules in the bulk of the solid
Upon size reduction of particles within a dispersion system, the solid particles tend to ?
agglomerate or stick together
Why do solid particles tend to agglomerate or stick together upon size reduction?
To attempt to reduce the
and hence the
surface free enrgy
displacement of surface air and contact of the liquid with the solid surface
Wettability depends on an
affinity of the solid surface for the solvent molecules
For aqueous vehicles (Hydrophilic) what water miscible solvents may be used to facilitate wetting and dispersion?
glycerin, alcohol, and proplylene glycol
What is used for hydrophobic particles to facilitate wetting and dispersion?
surface active agent (surfactant
is used to reduce interfacial tension between the particles and vehicle
A tightly bound layer of solvent and counter-ions exists on the solid surface
What does presence of counter-ions in the stern layer do for our dispersed solids?
It shields the solid surface charge and decreased the electrical potential across the stern layer
the potential difference between the shear planeand the electrically neutral bulk medium
of a dispersed solid phase dictates
the magnitude of electrical repulsion between the particles
The shielding of the solid surface charge by added counter ions increases , as ___?
of any electrolyte increases
of the couter ion increases
Higher zeta potentials increase _________ and decrease _______
repulsive forces between the suspended particles, the attractive forces at the secodnary minimum
IF particles can overcome th repulsion barrier and approach the primary minimum, particles _____?
come together and compact particle aggregation (
formation of a non-dispersible hard sediment of the dispersed phase
suspensions where particles are in flocs
tangential force applied per unit area which produces
Rate of shear
change in velocity with distance
rate of shear increases proportionally as shear stress is increased
In a Newtonian liquid, viscosity stays
In a newtonian liquid, if there is higher viscosity, then?
Higher shear stress is required for the same rate of shear, and greater resistance to flow
Plastic flow is not observed until ____?
a minimum shearing stress is applied (also known as the yield value )
the yield value the material exhibits ?
elastic behavior (returns to its original position after stress)
the yield value the system often exhibits?
In a Pseudoplastic System, viscosity is?
NOT constant and
with increase in shear stress (
Dilatant systems exhibit ?
increased resistance to flow (
) with increasing rate of shear (
speed at which particles of sediment drops based on radius and density; bigger particles drop faster
How in terms of stoke law, what would we change to slow down settling
decrease the diameter of the particles and add a viscosity building agents
Deflocculated or flocculated system, Which has a higher rate of sedimentation?
Flocculated systems, because loosley bonded particles
Deflocculated or flocculated system,which system takes longer to sediment?
Deflocculated or flocculated system, which system can easily and readily re-disperse ?
Flocculated system because it's sediment is loosley packed
For an ideal suspension, te sedimentation volume ratio (F) equals
1 and has no apparent sediment
Flocculation increases ?
Degree of flocculation provide a measure of the ?
extent of increase in the sediment volume achieved by flocculation
As the degree of flocculation in teh system decreases , the value of B ?
What are the 4 desired features of a pharmaceutical suspension? (specific)
-A properly prepared suspension should settle
and be readily dispersed upon gentle shaking
-Particle size should remain fairly constant through long periods of undisturbed standing
-The suspension should pour readily and evenly from its container
-It should be grit free and smooth
Coagulation occurs when
particles overcome the repulsion barrier to form
Caking occurs when
particles (deflocculated or aggregated) sink to the bottom of the container and the weight of the powder colummn forces the particles together, where they form stong inter-particulate interaction and are difficult to re-disperse
Surfactants purpose, (Hint: 3 of them)
decrease interacial tension, promote wetting of solids, and facilitate dispersion
Examples of nonionic surfactants
Pluronics (poloxamers), Sorbitan esters of fatty acids, and tweens (polysorbates )
high (positive and negative) zeta potentials
the suspension is
deflocculated and caking eventually occurs upon sedimentation
low zeta potential value
on either side of zero, the attractive forces are
sufficient to form a
(as seen by the plateu in the sedimentation volume curve)
insufficient bridging to become flocculated
particle bridging and flocculation
complete surface coverage of particles, steric hingerance, and *deflocculation
Structured vehicles provide a
viscous medium to slow down sedimentation of particles
Examples of aqueous solutions of polymeric materials
methylcellulose , carboxymethylcellulose, carbomer, xanthan gum
Aqueous solutions of polymeric materials, generally result in what flow behavior ?
plastic or pseudoplastic flow behavior
Examples of clay and microcrystalline materials
magnesiym aluminum silicate, bentonite, Kaoline, and fumed silica
Clays and microcrystalline materials can be used to
'bulk up' the solid content of the suspensions
Examples of buffering agents used in suspensions
citrate, phosphate , acetate buffers
The aspect of a product that the patient experiences through the senses (taste, sight, smell, and touch)
Why is addition of antimicrobial preservatives important for a suspension?
Microbial growth may be promoted by
Several formulation components
like thikners, non-ionic surfactants, sweeteners, ect.
Example of antimicrobial preservatives for suspensions
parahydroxy benzoic acids, benzoic acid/sodium benzoate, and sorbic acid/potassium sorbate/sodium sorbate
Binding of preservatives to polymers or surfactants in a formulation may decrease the
free concentration of the preservative and hence their activity in the formulation
An emulsion is a
mixture of two
What are the two classification of emulsions?
Oil-in-water and Water-in-oil
Oil-in-Water is suitable for
oral, parenteral, and topical routes of delivery
What emulsion is miscible with water and aqueous diluents as water is the continuous phase?
What emulsion is NOT with aqueous diluents as oil is the continuous phase?
Water-in-oil (w/o) is suitable for
exclusively for external application
Emulsion type will depend mainly on the
volume ratio of the oil and aqueous phases
and the types of
Tne phase in the emulsions that is present in greater concentration generally tends to be the _______?
Advantages of Emulsion Dosage Forms
-Allows for preparation of a relatively stable
mixture of two immiscible liquids
-Enables intravenous administration of an oil
Critical emulsion attributes
-The droplet size of the dispersed phase should remain fairly constant (
minimal coalescence of droplets
-consistency should be appropriate for use
Creaming of an emulsion
An unstable emulsion in which fat globules rise to the top of an emulsified mixture
When Pip < Pcp , what kind of emulsion is this?
Do droplets rise or settle in a O/W emulsion?
Do droplets rise or settle in a W/O emulsion ?
When Pip > Pcp, what kind of emulsion is this?
When droplets of an emulsion come in contact with each other, the emulsion will?
spontaneuously (decrease in the free energy)
When a combination of creamin and coalescence in an emulsion, then this will eventually happen?
phase seperation or craking of an emulsion
How can we prevent or reduce the rate of coalescence of internal phase droplets of emulsions?
proper selection of emulsifying agents
Examples of surfactants used for emulsions
Sodium Lauryl Sulfate, Cetrimide, and Poloxamer
and facillitate breakdown of the internal phase into small droplets (increase in interfacial area)
Surfactants may also prevent coalescence of droplets by...
coherent monolayer at the interface
of the droplet
If the emulsifier is ionized, Surfactants will confer a.......
surface charge to the droplet and might prevent coalescence due to repuslive forces between droplets
Examples of anionic surfactants
Sodium stearate, Triethanolamine stearate, calcium stearate (soaps)
Examples of cationic surfactants
-Bears positive charge
Bancroft's rule states: The phage in which an emulsifier is
constitutes the continuous (external) phase
High Hlb Surfactants are....
more soluble in water and o/w emulsions
Low HLB surfactants are ...
more soluble in oil phase and w/o emulsions
Non-ionic surfactants are not susceptible to .....
pH changes and presence of electrolytes
Non-ionic surfactants provide....
steric stabilization against coalescence and decrease in interfacial tension
HLB values < 10
HLB values above 10
Hydrated lyophilic colloids have little or no effect on...
Hydrated lyophilic colloids form....
multi-molecular films around the droplets, that coat the droplet surfaces and resist coalescence by forming a mechanical barrier
Finely divided solid particles functions as emulsifying agents?
they orient at interfaces and form a barrier to coalescence
examples of finely divided solid particles
Bentonite, Veegum, Magnesium hydroxide
Auxiliary emulsifiers function by...
increasing viscosity (thickening agents) or by forming a gel structure that provides a barrier to coalescence of droplets
Examples of auxiliary emulsifiers
Glyceryl monostearate, cetyl alcohol, cetostearyl alcohol, and stearic acid
Emulsion stabilization mechanisms
Repulsion due to like surface charges
2. Physical hindrance of coalescence by
tightly packed surfactant molecules
at the interface 3. Physical hindrance by
bridging of droplets by polymer strands
impeding close approach of droplets 5.
solid particles at the interface
physically hindering coalescence
Emulsion de-stabilization factors
1. Temperature changes 2. microbial growth 3. incompatibilities
A viscous preparation that is not pourable and does not flow under
shear stress at room temperature BUT exhibits
on skin and mucous membrane surfaces
Uses of semisolids
-protect the skin or mucous membrane from chemical or physical irritants -promote hydration of the skin -provide a vehicle for applying medication
semisolid emulsion dosage forms
Creams often contain .....
more than 20% water, and/or typically contain less than 50% hydrocarbons, waxes, polyols as the vehicle for the drug
Creams can be formulated as....
either a water-in-oil emulsion (cold cream) or as an oil-in-water emulsion (vanishing cream)
Characteristics of an ideal cream (or any other semi-solid)
non-irritating, non-allergenic, non-staining, able to be accurately dosed, easy/convenient to apply, and doesn't support bacterial/fungal growth
An advantage of water-washer bases in o/w emulsions are that they can...
be applied on
moist skin lesions
because o/w emulsion allows the base to absorb (mixt with) any wound exudate
Water-washable bases working by forming....
a semipermeable film at the site of application upon evaporation of water
Ointment vehicles usually contain....
less than 20% water
(and volatiles), and
more than 50% hydrocarbonds, waxes, or polyols
Active ingredients of ointments can be....
dissolved, suspended or emulsified in the base
Characteristics of oleaginous bases
Emollient (softening of the skin), Occlusive, NOT water washable, hydrophobic, greasy
Occlusive bases increase
skin hydration and hence serve as
(use on dry scaly lesions help rehydration);which may also help with increase permeation of active agents into the skin
Disadvantage of occlusive bases (or oleaginous bases)
Patient acceptability of these bases may be low due to the
of the base
Aborption bases contain
hydrophilic anhydrous materialsl, that can absorb water to form w/o emulsions
anhydrous bases contain
emulsifying agents that allow for incorporation of water
ointments with a high concentration of solid particles in an fatty vehicle
Characteristics of water-soluble ointment bases ?
contain only water soluble components (
), usually anhydrous, non-occlusive
Topical products deliver a drug into the skin to treat...
local skin condition (ex: psoriais )
Topical products site of action is the ....
lower layers of the skin (dermis and epidermis)
creams, lotions, ointments, or gels
(topical products) Drug partitions between the vehicle and the stratum corneum components and can be transported to the lower skin layers via either:
1. transcellular route(through the cells of the stratum corneum) 2. Intercellular route (between the cells of the stratum corneum) 3. Transfollicular route (through the hair follicles)
are designed to deliver drugs through the skin into the systemic circulation
What bases are preffered for dry conditions? Also Why?
Oily bases because they help with softening and moisturizing the skin
What bases are preffered for moist or 'weeping' conditions?
involved reduction in the
of a solid by triturating it in a morter, mixing on a slab with
small amount of the base
material, or with liquid
The objective of levigation is the ensure appropirate ....
particle size reduction, wetting and dispersion of the drug substance
glycerin, propylene glycol, polyethylene glycol 400, polysorbate 80
used for water-washable and water-soluble bases
Mineral oil castor oil, cottonseed oil
used for hydrocarbon bases and absorption bases
solvents for ointments
Water, alcohol, isopropyl alcohol glycerin, pyopylene glycol, polyethylene glycol 400
solvents for ointments
castor oil, cottonseed oil, olive oil, corn oil, isoproyl myristate
contain gelling agetns which are either...
1. suspensions of small inorganic particles (magnesium hydroxide gell, bentonite magma),
, 2. polymer solutions with the polyerm chains interpenetrated by the liquid solvent
Gels consists of at least two contituents :
a condensed mass "enclosing and interpenetrated by a liquid"
gels in which the matrix contains a high water content
The gel-forming particles or sovlated polymer molecules form a
3D structure which ...
restricts the movement of the solvent molecule, increasing internal friction, and thus provides resistance to flow (increased viscosity)
Random coils (gel structures)
synthetic polymers such as cellulose derivatives
Helix (gel structures)
an intertwined molecular chain structure;
a more ordered structure
(xanthan gum and starch)
Stacks (gel structures)
results from cross-linking of polymer chains by divalent cations (calcium alginate)
House of cards (gel structure)
clay a particles form such networks
House of cards gel structure results from....
the alignment of the positively charge edges with the negatively charged flat surfaces of the particles (bentonite and veegum)
liquid phase is water (gel network can be inorganic or organic)
Examples of inorganic hydrogels
Silica gel, bentonite, Veegum, aluminum hydroxide gels
Examples of organic hydrogels
pectin, sodium alginate, poloxamer, hypromellose, sodium carboxymethylcellulose, carbomer
liquid phase is organic/non-aqueous
Examples of organogel
Single phase gels are
Single phase gels
organic macromolecules distributed throughout the liquid, with no apperent boundaries between the dispersed phase and the liquid
Single phase gels may use...
aqueous, alcoholic or oil liquid phases
Two phase gels
small discrete particles forming the gel network
Example of two phase gels
Aluminum hydroxide gel, magnesium hydroxide
Gel formation relies on.....
the gelling agent conferring a network structure to entrap the liquid phase
As the gelling agent concentration increases....
intermolecular distances decreases, which yields a gel with greater viscosity
Hydrogels of cellulose derivatives examples
Methylcellulose, Hydroxyethylcellulose , carboxymethylcellulose
(poloxamer 407 gel example) As temperature increases,....
the molecules aggregate into
, this due to dehydration of the hydrophobic polyoxypropylene blocks
how do micelles form gel structure?
The spherical micelles with a dehydrated hydrophobic core and hydrated swollen hydrophillic chains form aggregates on
further temperature increase
which forms the gell structure
Thermo-gelation of poloxamer is....
by change in temperature
Gel consistency depends on
the poloxamer concentration
Examples of Natural gums
alginates, carrageenan, guar gum, xanthan gum, tragacanth, and pectin
Examples of carbomer
cross-linked carboxyvinyl polymer, Cabopol
Examples of Poloxamer
Tri-block copolymer with polyoxyethylene and polyoxypropylene blocks
Example of Colloidal dispersed solids
Colloidal silica, clays (magnesium aluminum silicate, veegum)
colloids/disperse systems that are composed of 2-3 distinct phases
What are the 2-3 distinct phases of foam ?
1. a hydrophilic liquid contiuous phase containing a surfactant/foaming agent 2. a gaseous disperse phase 3. a hydrophobic dispersed phase (optionally
(usp definition of foam) When the emulsion is disharged from the container, ....
the propellant vaporizes into a gas that is trapped by the aqueous solution and forms a foam
Examples of propellants
HFA, butane, nitrous oxide, carbon dioxide
Examples of foaming agents(Surfactants)
sodium lauryl sulfate, sodium stearate, sodium oleate, sodium dodecyl sulfate, dioctyl sulfosuccinate
Examples of foam stabilizers
xanthan gum, hydroxypropylmethylcellulose, methylcellulose, alginates, agar
Examples of solvent/cosolvents (foam)
water, propylene glycol, polyethylene glycol
Examples of emollients (foam)
isopropyl palmitate. mineraly oil, cetearyl alcohol, lanolin, glycerol monstearate, isopropyl myristate
Substances that absorb moisture or promote the retention of moisture.
Examples of Humectants in foam
glycerin, propylene glycol, triacetin
Examples of pH modifiers in foam
sodium hydroxide, hydrochloric acid, citric acid, acetic acid, lactic acid
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