Dosage forms exam 1 my flashcards
What are 3 types of liquid dosage forms?
SolutionEmulsionSuspension
What is the definition of a solution?
A homogeneous molecular dispersion
What is the definition of an emulsion?
System of 2 immiscible liquids where one is dispersed as dropletsOil in water, water in oil
What is the definition of a suspension?
Solid in water or oil
What are 3 advantages of Solution dosage forms?
Homogeneous- No content uniformity issuesGood bioavailabilityEasy to manufacture
What are the 6 components of a solution?
Active ingredientSolventBufferPreservativeAntioxidant- Chelating agentFlavor/sweeteners
What is the definition of a buffer?
A solution of a weak acid and the salt of its conjugate base
What is the function of the weak acid component in a buffer?
It removes the added base (OH-)
What is the function of the salt component in the buffer?
It removes the added acid (H+)
What is the definition of buffering capacity?
The ability of buffer to resist a change in pH due to addition of acid or base
What does C stand for in the buffering capacity equation?
C= Total buffer concentrationC = [HA] + {A-]
What are 4 common buffers?
Citric acidacetic acidglycinephosphoric acid
What are 2 things to keep in mind when selecting a buffer?
- Use a pH that provides maximum drug stability2. Minimize irritation by making pH equal to that of the body fluid
What are 3 things you can do to minimize irritation when the pH cannot be matched to the surrounding fluid?
- Minimize buffering capacity2. Reduce volume3. Administer slowly
What is the purpose of antimicrobial preservatives?
- Protects the patient from pathogens2. Maintains the potency and stability of dosage forms
What is the mechanism behind antimicrobial preservatives?
Adsorb to the bacterial membrane and disrupt it- often lyse the bacteria or prevent proliforation
What are the properties of the bacterial membrane that preservatives use to bind?
The negatively charged surface membrane and the lipophilicity of the membrane allows for hydrophobic interactions
Which antimicrobial preservatives use the lipid solubility to bind?
Alcohols, acids, esters
Which antimicrobial preservatives use the electostatic interactions to bind?
Quaternary ammonium compounds
How much bacterial content is allowed in ampules- injectable solutions?
None, solution must be sterileFor single dose vials no preservative is needed
How much bacterial content is allowed in multiple dose vials?
None, must be sterileMay contain up to 10 doses, require preservatives
How much bacterial content is allowed in opthalmic solutions?
None, must be sterileMust contain a preservative if packaged in a multiple dose container
How much bacterial content is allowed in oral liquids?
Less than 100 pathogens/1 mLNeed preservatives for multiple dose packages
How much bacterial content is allowed in oral solids?
Less likely to carry bacteria than liquid formsCan be contaminated with salmonellaCheck raw materials and make sure facility is clean
Characteristics of ideal preservatives?
- Effective in low concentrations against a wide variety of organisms2. Soluble in formulation3. Non toxic4. Stable
List 5 pharmaceutical preservatives?
- Alcohols2. Acids3. Parabens4. Quaternary Ammonium Compounds
Characteristics of ethanol as a preservative?
Requires a concentration of greater than 15 percentoral products onlycan be lost because it is so volatile
Characteristics of Benzyl Alcohol as a preservative?
Local anethetic actionBurning taste- not used orallyWater soluableStable over wide pH rangeHighly used in parenterals
Characteristics of acids as preservatives?
Only active in the unionized form - lipid soluable because they have more affinity for the microbial membrane
What products are Benzoic acid utilized in?
Oral products
What products are Sorbic acid utilized in?
Oral products (excellent for molds/yeast)
Characteristics of Parabens as preservatives?
Widely used orallyLipophillic and less lipophillic varieties (depends on length of hydrocarbon R group) low soluabilityCan cause skin sensitization when used dermatologically
What factors effect the action of preservatives?
pH (ionized vs. unionized acids)Complex formation (can’t be used when complexed)Adsorption by solidsChemical stability (shelf life)
How can oxidation be prevented?
Add excipients
What excipients can be used to prevent oxidation?
Vitamins, essential oils, fats, oils
What are the 2 kinds of oxidation?
Auto- Oxidation (spontaneous)heat/light/metal/peroxide initiated (creates free radicals)
What are the 3 kinds of antioxidants?
Free radical scavengersreducing agentschelating agents
Mechanism for Free radical scavengers?
Retard/delay oxidation by rapildy reacting with free radicals
Mechanism for reducing agents?
Lower redox potential than the drug so it is more readily oxidized
Mechanism for chelating agents?
antioxidant syngergists, remove trace minerals
What are the 2 phases of an emulsion?
dispersed phasecontinuous phase
What properties of the emulsion does the continuous phase dictate?
the organoleptic propertiestaste, smell, feel
What forms can an emulsion come in?
oral, external, IV
Can oils be injected IV?
Yes- if can make it as an emulsion
How are forces dispersed in the bulk phase of an emulsion?
Molecules are all attracted to each other equally in all directions
How are forces dispersed at the boundary phase of an emulsion?
Forces are unequal, molecules all exhibit different forceswater- H bond, oil- london dispersion forces
What is interfactial tension?
Caused by the imbalance between force dispersion between the bulk phase and the boundary phase- result is constant spontaneous mvmt between phases and fewer molecules at the interface per unit area- increasing the area of contact btw the 2 phases creates tension-** the force of this tension per unit length of interface is Interfacial tension
What kind of tension is interfacial tension?
Liquid- liquid
What kind of tension is Surface tension?
liquid- air tension
What increases interfacial tension?
Stronger intermolecular forces in the bulk phase(intermolecular forces are reduced at high temp)
What are the 3 types of emulsifying agents?
Surfactive agentshydrophilic colloidsfinely divided solid particles
What class does surfactants fall into, amphiphillic, hydrophillic or hydrophobic?
Amphiphillic
What affect does high surfactant concentration have on surface tension>
it reduces surface tension (to a certian point- critical micelle concentration)
What is hydrophile-lipophile balance (HLB)?
A measure of the relative contributions of the hydrophillic and lipophillic regions of a surfactant- ranges from 0-20 for nonionic surfactants
Low HLB = ______ lipid solubility?
Greater
What does “a” stand for in the HLB equation?
“a”= fraction of surfactant 1 in the surfactant mixture
What happens when the surfactant concentration increases above the critical micelle concentration?
The surfactant molecules self associate into micelles
What emulsions are hydrophilic colloids used in?
O/W emulsions
How do hydrophilic colloids work?
They increase the viscocity of water and form a multimolecular film on the surface
Do hydrophilic colloids lower interfacial tension?
NO
How do finely divided solid particles work?
They adsorb at the interface and form a film of particlesHydrophilic and hydrophobic forms
HLB greater than 10
W/O
HLB less than 10
O/W
When is a finely divided solid particle hydrophillic?
if the contact angle is less than 90 degreesO/w
When is a finely divided solid particle hydrophobic?
if the contact angle is greater than 90 degreesW/O
What is the Phase volume ratio?
Volume of Oil phase/Total volume of the emulsion
Phase volume ratio of 0-26%?
O/W
Phase volume ratio of 26-74%?
Either O/W or W/O
Phase volume ration of 74-100%?
W/O only
What 3 ways can an emulsion become unstable>
- Creaming2. Coalescence3. Phase inversion
Stokes Law: What does V stand for?
V= velocity of sedimentation(-) = floating droplets high IvI- settles or floats frequently
Stokes Law: What does d stand for?
d= diameter of the droplets
Stokes Law: What does Pi stand for?
Pi = density of the internal phase
Stokes Law: What does Pe stand for?
Pe= Density of the external phase
Stokes Law: What does n stand for?
n = viscosity of the external phase
Is creaming reversible?
Yes, as long as the interfacial film is effective in maintaining the integrity of the individual droplets
Is coalescence reversible?
NO, leads to a layer of oil and water- brokencan’t fix by shaking
What causes phase inversion?
a phase volume ration of greater than 74%hard water can cause it also
When making an emuslion, do the aqueous solution and oil solution need to be heated to the same temperature to mix?
Yes, then cooled slowly and passed through a homogenizer
What is a suspension?
Liquid preparation where solid particles are dispersed through a liquid phase in which the particles are not soluble.
Advantages for suspensions?
SolubilityChemical StabilityTaste/PalatabilityDose is flexibleFaster Dissolution than tablets
What is the kinetic order of solutions?
1st order (fast)
What is the kinetic order if suspensions?
Second order (slower rxn, faster dissolution and more bioavilability)
What are the components of a suspension?
Active ingredientVehicleBufferPreservativeFlocculating agentStructured vehicle systemwetting agentantifoming agentflavor/sweetener
Required characteristics of a suspension?
Suspended particles should settle slowlyParticles that settle should be able to re-disperseThe suspension must flow but not to muchParticle size must remain constant
Stokes Law: Ps
Ps = density of solid
Stokes Law: Pl
Pl = density of liquid
Micropulveration
10-50umMost oral and suspensions
Fluid Energy Grinding
<10 umParenteral and opthalmic suspensionsShearing action of high velocity air
Spray drying
<5umnSolution of drug is sprayed and dried by air
what are the 3 types of suspensions?
dispersed suspensionflocculated suspensionstructured vehicle system
DeltaG = ?
Increased surface free energysuspension is stable when G = 0
Ys/l = ?
Interfacial tension between solid and liquid
DeltaA = ?
increase in surface areawant small particles–> high deltaA
What 2 forces decrease particle size?
aggregationcrystal growth
Van der Waals forces, attractive or repulsive?
attractive, over moderate distances but gets very strong close to the surfacenot affected by formulation factors
Electrostatic forces, attractive or repulsive?
Repulsive, due to the surface charge on the particleCan be affected by formulation
Steric forces, attractive of repulsive?
Repulsivecan be controlled by the formulation
Hydration forces, attractive or repulsive?
Repulsivenot affected by formulation
Net effect of interparticle forces?
Repulsive force (+) little effect when particles are far apartAttractive force (-) dominant when particles are close
Dispersed suspension what forces are dominant?
RepulsiveParticles repel each other and don’t aggregateparticles settle and are difficult to re-suspend
Controlled flocculation what forces are dominant?
Repulsive and attractive forces are balanced
How does a flocculated suspension work?
At the secondary minimum the repulsive force is reduces a bitwhen floccules settle, they are easy to re-disperse
What type of sediment does a flocculation form?
High volume
What are some examples of flocculating agents?
ClaypH manipulationElectrolytesNon-ionic/ionic surface active agents
What type of suspensions is clay used in?
Oral suspensions
What type of suspension will you alter the pH in?
parenteral solutions
How do electrolytes create flocculations?
Reduces the electrical barrier between particles only works at ideal concentration
Structured Vehicle system
Thickens the dispersion medium to suspend the particles
Does the structured vehicle interfere with the availability of the drug?
NO
What are 2 types of structured vehicles?
Claypolymers
Rheology
The study of flow characteristics
What is shear rate?
dv/drthe difference of velocity (dv) between 2 planes of a liquid separated by a distance (dr)
What is shear stress?
Fthe force per unite area required to bring about flow
What are the 2 kinds of shear stress?
Newtonian flownon-newtonian flow
What are the 3 kinds of non-newtonian flow?
PlasticPseudoplasticDilatant
what is the shape of a newtonian flow curve?
Linearslope is constant at all shear stress
What is the shape of a plastic flow curve?
liquid doesn’t flow until a certian shear stress is reached
What is the shape of a pseudoplastic curve?
high force = high flow
WHat is the shape of a dilatant curve?
high force = low flow
What is f( yield value) mean?
Threshold of shear stress necessary to initiate flow
Shear thinning
The strength of the attractive force of the secondary minimum
Pseudoplastic suspensions?
No stresstypical polymer Shear thinning
Thixotropy
the ability of the system that was disturbed by an applied shear stress to return to the undisturbed structure
Which kinds of rheology suspensions exhibit thixotropy?
plastic and pseudoplastic
What does thixtropic suspensions form at rest?
A rigid gel matrix to stabilize the suspensions (shear stress from shaking makes it more liquid)
Is there sedimentation with a structures vehicle suspension?
NO
What is wetting?
displacement of air from the surface of a particle by the vehicle
What does contact angle have to do with wetting?
High angle indicates poor spreading
What is the importance of a wetting agent?
for rough particles, an aqueous vehicle will not enter the pores and the particle will float due to the high air content- wetting gent reduces the surface tension of the aq vehicle to allow water to enter the pore
