Formulations and Compounding Final Exam Flashcards
What is the purpose of sonication and extrusion?
Sonication and extrusion are done to reduce the size of the hydrated LMV suspension.
______ water is supplied for hand and equipment washing. ________ water must be used for compounding nonsterile drugs & rinsing equipment & utensils. It has a microbial limit of _______.
Water used to prepare a sterile prep must be either:
1 - _________
2 - _________
3 - _________
Potable water for hand and equipment washing
Purified water for nonsterile preps.
Microbial limit of less than or equal to 100 CFU/mL
1 - water for injection
2 - sterile water for injection
3 - bacteriostatic water for injection
Identify the type of liposome:
- prepared by grafting polymer at the surface (increases circulation time in the blood; PEG is usually attached)
- PEGs create a barrier around them to reduce interactions with endogenous molecular and cellular components
- evades recognition by immune system because of PEG
Long-Circulating (Stealth)
Identify the purpose and examples of the excipient:
Humectant
Purpose - prevents preparation from becoming dry and brittle
Examples - glycerin, propylene glycol
List the steps involved in wet granulation (in general)
- Weigh and mix the drug, diluents, and disintegrants
- Pass the powders through a sifter
- Mix binder and water in a heated container (forms granulating fluid)
- Add the granulating fluid to the powder -> forms damp mass
- Screen the damp mass through suitable size screens to make granules
- Dry the granules
- Pass through granules through another smaller mesh
- Add lubricants and glidants
- Compress (aka actually form the tablet)
Give an example of a propellant free MDI.
Respimat
What are SEDDS and at what size ranges are they found?
SEDDS = self-emulsifying drug delivery systems
Isotropic mixtures of natural or synthetic oils, solid or liquid surfactants, and co-solvents/surfactants
- the emulsify spontaneous to produce fine oil-in-water emulsions in contact with the aqueous phase
Size range = 100-300 nm
Bioavailability of a drug is determined by
extent of drug solubility and permeability
The maximum quantity of alcohol in OTC medicine is ____ for products labeled for people 12+, ____ for ages 6-12, and ___ for under 6 years of age.
12+ = 10% max
6-12 = 5% max
< 6 = 0.5%
when the solute concentration in bulk is equal to or less than ____% of the drug’s solubility, the solubility drives the dissolution rate. This is referred to as ________.
What is the opposite of this?
10%; sink conditions
Non-sink conditions exist when the concentration is greater than 10% of the drug’s solubility
What is meant by “ion trapping” after oral absorption?
when extracellular and intracellular pH is different, the ionized fraction of solute in and out of the cells becomes different.
- ionized fraction increases where pH favors ionization, so a drug may get trapped on one side of the cell membrane (in or out)
- when ionized fractions go up inside the cell, the intracellular drug concentration also goes up (this could be good or bad)
An ophthalmic solution may contain what excipients?
- vehicle
- buffers
- tonicity adjustors
- preservatives
- antioxidants
- viscosity inducing agents
________ release allows the drug to be released in pulses separated by certain delays in between
Pulsatile
What is a liposome?
A vesicle-like structure composed of one or more lipid bilayers encapsulating an aqueous core
(phospholipids are usually used as lipids)
________ is an index of a compound’s polarity (increase = increased polarity)
Dielectric Constant
Why is it recommended you moisten the tips of glycerinated gelatin based suppositories?
Because they are hygroscopic in nature and may have a dehydrating effect on the rectum
What are the general rules of solubility for inorganic molecules?
1 - if both ions are monovalent, the attractive forces are easily overcome and the solutes are generally water soluble
2 - if they’re multivalent, poorly water soluble
3 - salts of alkali metals = usually water soluble
4 - ammonium & quaternary ammonium salts = water soluble
5 - nitrates, nitrates, acetates, chlorates, lactates = water soluble
6 - sulfates, sulfites, tihosulfates = generally water soluble
7 - hydroxides and oxides = generally water soluble
8 - phosphates, carbonates, silicates, borates, hypochlorites = generally water insoluble
_________ generate a voltage when mechanical pressure is applied
Piezo-electric crystals
List the advantages and disadvantages associated with ophthalmic ointments.
- *Advantages**:
- longer contact time
- greater total drug bioavailability
- *Disadvantages**:
- slower onset and time to peak absorption
- dosage variability is greater than with solutions
- interfere with vision unless use is limited to bedtime instillation
- ophthalmic ointments must be sterile and free from particulate matter
In the case of nasally inhaled aerosols, the majority of inhaled particles deposit in the..
For delivery to the lungs, drugs are inhaled ______
nose and pharynx
orally
What kind of needle should be used when drawing the contents of an ampule into a syringe?
Why?
A 5 micron filter needle should be used because glass particles may have fallen into the ampule when the top was snapped off
What are the limitations of conventional drug delivery systems?
- whole body exposure
- affect non-target organs and tissues
- drug wastage and even toxic effects
Polymers used in microencapsulation include…
Gelatin
Polyvinyl Alchol
Ethyl Cellulose
Polyvinyl Chloride
Define the following:
1 Syneresis
2 Swelling
3 Imbibition
4 Thixotropic
- Syneresis - upon standing for some time, gels shrink because some of the liquid squeezes out of the system
- Swelling - opposite of syneresis; gel takes up some liquid and increases in volume
- Imbitition - taking up a certain amound of liquid but no measurable increase in volume
- Thixotropic - semisolid upon standing but becomes liquid on agitation and again semisolid upon standing
Ionization typically has what effect on solubility?
Ionization of the solute generally increases solubility
The 3 major components for a drug targeting system are
1 - the drug (for therapeutic effect
2 - carrier system (controls distribution and protects from metabolism and early clearance)
3 - homing device (delivers drug to specifc area)
What are the general rules of solubility for organic solutes in water?
1 - one polar function group usually solulbe to a chain length of 5
2 - branched chain > straight chain solubility
3 - solubility is inversely proportional to molecular weight
4 - the more structure similar, the greater the solubility
5 - more polar groups = greater solubility
6 - halogens tend to decrease solubility
7 - weak acids/bases are less soluble; salts of them are more soluble
8 - the only types of salts that are considered high dissociable are formed when: strong acid + strong base; strong acid + weak base; weak acid + strong base
Inorganic gels are usually _______
Organic gels are usually ______
What are jellies and xerogels?
Inorganic = usually 2 phase
Organic = usually single phase
Jellies are a class of gels in which the structural coherent matrix contains high proportion of liquid (usually water)
Xerogel is formed when the liquid is removed from a gel and only the framework remains
Identify the purpose and examples of the excipient:
Levigating (wetting) Agent
Purpose - can help reduce the particle size or also help in good penetration of the dispersion medium into the dispersed phase
Examples - mineral oil, glycerin
________ dosage forms maintain their shape until a force is applied
semisolid
Identify the purpose and examples of the excipient:
Diluents (fillers)
Purpose - fill volume/size
Examples - starches, calcium salts, lactose, cellulose, mannitol, sorbitol
What advantages and disadvantages are associated with sugar coating tablets?
Advantges:
- protects against degradation from the air
- masks the bitter taste or bad smell
- enhances elegance/appearance
- prevents unwanted contact with drug
Disadvantages
- Not everyone likes the candy-like taste
- Excellent medium for microbial growth
- Tends to crack
- Hygroscopic
- Tabelt weight increases by 50-100%
_______ is a form of sticking when a small portion of the tablet or granulation sticks to the punch face and it grows with each revolution of the press
picking
The rate of diffusion in the lungs depends on
mucus thickness
drug molecular weight
drug mucus interaction (binding of positively charged drugs with mucus glycoproteins)
Identify the purpose and examples of the excipient:
Hydrophilic solvent
Purpose - liquid with high miscibility with water; used to dissolve solutes
Examples - PEG (polyethylene glycol), alcohols
List the desired properties of a good suspension.
- Should be readily re-dispersed upon gentle shaking of the container
- Homogenous during the period between shaking the container and removing the required dose
- Pour readily and evenly from the container
- Particle size should remain fairly constant throughout periods of undisturbed standing
- Should not form a cake upon standing
What is pegylation and what is it used for?
It is used in passive targeting as a pay to prevent macrophages from phagocytosing drugs/drug carriers.
Carriers and/or drugs can be coated with PEG. The PEG coating reduces adsorption of opsonins and slows phagocytosis.
It also delays uptake by the liver and increases circulation time.
True or false: nasal cilia, tracheal cilia, and bronchi cilia all beat tward the throat.
True
__________ is a two-chamber push-pull osmotic system that releases drug in the morning to control blood pressure.
________ is a push-pull system that delivers drug for 24 hours.
_________ is a matrix formulation that consists of an external coat for slow release and an internal core for fast release.
Covera-HS (night time Verapamil for morning control)
Procardia (nifedipine 24 hour drug)
Adalat (nifedipine; biphasic release pattern)
which type of topical is used on mucous membranes?
creams
Small Volume Parenterals are packaged in:
Small plastic bags (called a minibag of 50-100mL)
Ampules
Vials
Pre-filled syringes
The most ideal particle size for pharmaceutical suspensions is
1 to 50 micrometers
Gelatin coated tablets are also known as
Gelcaps or Caplets
Absorption of suppositories depends on…
- physiological factors
- colonic content (greater when empty)
- blood circulation
- pH and lack of buffering capacity of the rectal fluids
- physicochemical nature of the drug and its ability to traverse the physiologic barriers to absorption
- nature of the suppository base and its ability to release drugs
Flocculated vs Deflocculated:
- Particles are bonded weakly and settle rapidly – ?
- Particles settle separately – ?
- Particles are easily resuspended – ?
- A distinct boundary exists between the liquid and sediment when the particles settle – ?
- Particles settle slowly – ?
- Paricles aggregate into a hard cake which is difficult to resuspend – ?
- Particles are bonded weakly and settle rapidly – flocculated
- Particles settle separately – deflocculated
- Particles are easily resuspended – flocculated
- A distinct boundary exists between the liquid and sediment when the particles settle – flocculated
- Particles settle slowly – deflocculated
- Paricles aggregate into a hard cake which is difficult to resuspend – deflocculated
What type of targeting utilizes polymer-drug conjugates?
Both active and passive.
In passive, the drug is conjugated with a water soluble polymeric backbone via a linker. This is useful with anticancer drugs because normal tissues will not allow the conjugate to enter, but tumors have the EPR effect.
In active, the polymer-drug conjugate is linked to a targeting moiety such as an antibody. (ex. conjugated with galatosamine (the homing device) to target certain cells)
For _______ granulation, either the API or diluent must have cohesive properties.
dry
What is a protectant and why would it be added to a parenteral preparation?
It is a substance added to a formulation to protect against loss of activity of active ingredients by some stress (such as freeze drying)
- they can be cryoprotectants (freezing stress) and lyoprotectants (drying stress)
- examples: PEG, mannitol, glucose, and trehalose
________ dosage forms contain 2 single doses of medication
repeat action release
What system was devised as an alternative to BCS?
Biopharmaceutics drug disposition classification system (BDDCS)
- takes into account the impact of metabolism and drug transporters (efflux and uptake/absorptive)
- when the major route of elimination is metabolism, permeability is high
- when the major route of elimination for a drug is renal and biliary excretion of unchanged drug, the permeability is low
Hydroxypropylcellulose is part of the formation of what ophthalmic treatment
Lacristert sterile ophthalmic insert used in treatment of dry eye syndrome
What are particulate carriers?
Nano or micrometer size lipid or polymeric drug delivery systems
______ are sealed glass containers that are used for liquid formulations only.
Ampules
What are the different classes of elixirs?
Nonmedicated (used in extemporaneous filling of prescriptions involving addition of a therapeutic agent or dilution of an existing medicated elixir)
Give examples of sugars that can be used to make hard lozenges.
Sorbitol and Mannitol
Tablets that dissolve in 15-30 seconds are called
rapid dissolve tablets (RDT)
What types of power can be used to generate aerosols?
electrical
pneumatic
mechanical
Identify what is contained in the upper respiratory tract and the lower respiratory tract.
Upper: nasal cavity, larynx, pharynx
Lower: trachea, primary bronchi, lungs
Describe the characteristics of an ideal solvent for a pharmaceutical dosage form.
- non-toxic
- non-irritant
- does not interfere with drug absorption
Identify the type of liposome:
- prepared by grafting or coating the surface with antibodies or antibody fragments
- can be stealth or non-stealth
Immunoliposomes
The particle deposition of droplets depends on
particle size and the anatomy of the respiratory tract
Which 3 methods can be used to compress tablets?
1 - Wet Granulation
2 - Dry Granulation
3 - Direct Compression
A _________ is a homogenous mixture of two or more substances.
Solution
_____________ is the process by which a solid, liquid, or gas forms a solution in a solvent.
Dissolution
What types of bases can be used to make soft lozenges?
- fatty base chocolate
- PEG base (most commonly PEG 1000 or PEG 1450)
- sugar acacia base
True or false: a solute will not dissolve if the solute-solvent forces of attraction are weaker than the individual solute and solvent intermolecular attractions.
True
Compare and contrast the different types of spacers.
- Simple tube extension
- Valved holding chamber
- contains a 1-way valve for the aerosol to remain within the device until the patient inhales
- Reverse flow device
- uses a bag which collapses upon inhalation
IFR is more important for devices that require the use of energy to generate drug aerosol, such as ______
DPI - dry powder inhalers
(an increase in IFR will produce particles of smaller size)
Which polymers are used in enteric coating?
cellulose acetate phthalate
polyvinyl acetate phthalate
diethyl phthalate
Compare and contrast flocculation, aggregation, and caking
Flocculation - the process of formation of flocs or conglomerates
Aggregation - particles adhere to each other by stronger forces to form aggregates or agglomerates
Caking - occurs due to the growth and fusion of crystals in the precipitates and produce a solid aggregate
The main components in an oral solution are
- Active ingredient
- vehicles
- sweeteners
- flavors
- colors
- preservatives
- buffers
- antioxidants
- perfumes
Hard lozenges are mixtures of ______ and other __________ in amorphous state.
They are prepared from aqueous syrup by heating _________ and other ingredients together, then pouring the mixture into a mold. The molds can be in the shape of a ______ or _______.
They will not disintegrate in the mouth but will…
What kind of drugs would not be suitable for incorporation into a hard lozenge?
Mixtures of sucrose and other sugars/carbohydrates
heating sugars
sucker or lollipop
will erode or dissolve over a 5-10 minute period
heat unstable drugs may not be suitable for incorporation into hard lozenges
What advantages do suppositories offer?
- avoidance of first pass metabolism
- convenient for patients unable to swallow
- achievement of rapid drug effect systemically
- ability to administer large doses of drugs
- suitable for unconscious patients
- pediatric populations
- low cost
- targeted delivery
- minimized systemic toxicity
- concentrated drug at the site of action
What types of lipids can be used to prepare liposomes?
Neutral (do not carry charge); examples: DSPE (distearoyl phosphatidyle-thanolamine), cholesterol, DSPC (distearoylphosphatidylcholine)
Anionic (negative charge); example: DMPG (dimyristoylphosphatidylglycerol)
Catioinc (positive charge); examples: DOTAP (dioleoyltrimethylammonium propane) and DODAB (dioctadecyldimethylammonium bromide)
The 3 most important barriers for particles to overcome (in the lungs) are
- Mucus barrier
- Mucociliary clearance
- Alveolar clearance
Why do you need film coating?
- protect against air, humidity, and light
- mask the bitter taste or bad smell
- alter dissolution profiles
- enhance appearance and elegance
What advantages are associated with powder dosage forms?
- administered easily to infants and young children
- rapid onset of action (because they can be readily dispersed in liquid and only require dissolution and not disintegration before absorption)
- can be applied to many body cavities, such as ears, nose, throat, tooth socket, etc.
- drugs tend to be most stable as solids
Other than ultra-sonic nebulizers, what kinds use Piezo-crystals?
static mesh and vibrating mesh (they’re both types of ultrasonic)
The permeability of the _______ portion of the nose is higehr than that of the ______ portion.
Because of this, fast absorbing drugs should be deposited in the _______.
Posterior > anterior
Posterior
How can sterility be achieved for ophthalmic dosage forms?
- filtering the final solution using a membrane filter < or equal to 0.2 micrometers
- packaging using a clean, particle-free, sterile container
- longer than 24 hours or multi-dose, a preservative may be added
- use aseptic technique in a clean and aseptic area
- use of laminar-flow hoods and proper garments
List the advantages and disadvantages associated with ophthalmic solution dosage forms.
- *Advantages**
- dosage uniformity
- little physical interference with vision
- *Disadvantages**
- relatively brief contact time
- contact time may be increased to some extent by inclusion of a viscosity-increasing agent such as methylcellulose
List the steps in filling of aerosols.
- Start with an empty can
- Add formulations to the can
- Fit the valve to the container (actuators can be fitted to the valve before the valve is crimped to the can)
- Add propellant via the valve (in this step, aerosols will be pressurized)
- Fit actuator
What purpose do binders serve in tablets? What types are there?
They add cohesiveness to powders and facilitate bonding of particles to form granules
types:
1 - natural gums and starches (acacia, gelatin, starch)
2 - synthetic cellulose derivatives (methylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone)
The 3 types of tablet coatings are
Sugar
Film
Enteric
What kinds of particulate carriers can be used for active targeting?
Liposomes and polymeric micelles
the particle surface is modified with proteins, peptides, antibodies, or polymers.
Ligands used are: folate, transferrin, and epidermal growth factor receptor (EFGR) because they are overexpressed in many tumor surface cells
using the equation that predicts the effect of temperature on solubility, what is the response if delta H is positive?
If delta H is negative?
If delta H is negative (heat releasing), then an increase in temperature will result in a decrease in solubility
If delta H is positive (heat absorbing), then an increase in temperature will result in an increase in solubility
Describe some benefits of microencapsulation.
- protects the product against degradation by pH and light
- masks color and taste
- improves release profile and shelf-life
Identify the purpose and examples of the excipient:
Anti-oxidants
Purpose - prevents oxidation
Example - ascorbic acid
Film coated tablets are…
- coated with a thin layer of either water-soluble or water-insoluble polymer that ruptures in the GIT
- more durable than sugar coating
- organic solvent or aqueous-based
- less bulky and time consuming
Identify the purpose and examples of the excipient:
Sweeteners
Purpose - provides sweetness to the preparation
Examples - aspartame, saccharin, glycerin, dextrose, lactose, mannitol, sorbitol, phenylalanine, stevia, xylitol
_________ is the amount of medication placed in the nebulizer.
__________ is the volume of the solution placed in the nebulizer.
Nebulizer Charge
Volume Fill
When classified based on composition and applications, what are the classifications of liposomes?
Conventional
Sterically Stabilized
Immunoliposomes (non-stealth and stealth)
Cationic
pH Sensitive
Define oral solutions in terms of dosage forms.
What are the advantages of using oral solution dosage forms?
Solutions are liquid preparations that contain one or more therapeutically active ingredient dissolved (dispersed) in a suitable solvent or mixture of mutually miscible solvents
Advantages:
- easy to swallow
- easy dose adjustment
- immediate absorption
- uniformity
- reduced side effects (irritation is reduced)
What factors affect drug availability in the eye?
- Rapid solution drainage by gravity, induced lacrimation (tears), blinking reflex, and normal tear turnover
- Low corneal permeability (acts as a lipid bilayer)
With _________ tablets, the bulk density is less than one and the tablets will float in the stomach. In the GI fluid, the polymer swells to form a boundary layer that prevents immediate entry of GI fluid into the tablets.
The polymeric layer then slowly wears away, giving rise to a new boundary layer
Hydrodynamically balanced tablets
Describe deposition by inertial impaction
- Most common mechanism for particles greater than 5um
- Inspired air changes the velocity and direction of movement
- Larger particles can’t change their paths at bifurcations and will impact on airways
- Increases at high air and turbulent flows in the trachea and major bronchi
- Increases with increases in: particle velocity, diameter, and density
- Occurs in the zones of highest airflow velocity in larger airways
Identify the purpose and examples of the excipient:
Coatings
Purpose - prevents degradation due to oxygen, light, moisture, and masks unpleasant taste
Examples - shellac, gelatin, gluten
The _____ dose is the labeled dose (written on the package)
The _____ dose is the amount contained in the metering unit.
The _____ dose is the amount leaving the device.
The _____ dose is the amount contained in particles.
Nominal
Metered
Delivered
Fine particle
Define Stability according to USP chapter 1191.
The extent to which a product retains, within specified limits, and throughout its period of storage and use, the same properties and characteristics that is possessed at the time of its manufacture.
When can preservatives not be used for ophthalmic preps?
- during eye surgery
- for use in traumatized eyes
intravitreal injections are placed into the _______.
injections into the anterior chamber of the eye are ________.
vitreous chamber
intracameral injections
Nasal sprays tend to deposit in the ____ nasal cavity, where airflow is high and mucociliary clearance is slow.
anterior
Why is the clearance of nasal spray slower than that of drops?
It deposits on the non-ciliated regions
What properties does glycerin offer in terms of being used as a pharmaceutical solvent
- colorless, odorless, viscous liquid
- excellent for drugs that are not easily soluble in water or alcohol
- dissolves a large number of salts, pepsin, tannin, gums, starches, etc.
- acts as a preservative at high concentrations
List and describe the types of ointment bases.
- Oleaginous base (aka hydrocarbon bases or greasy bases) - have an excellent emollient effect, difficult to wash out (immiscible with water)
- Absorption bases (absorb water w/o significant changes to consistency) - two types, emulsifiable (don’t contain water but can incorporate it) or emulsion (are W/O emulsions)
- Water-removable bases (water washable bases) - the external phase is aqueous (so easily removed from skin); are oin in water emulsions (O/W)
- Water-soluble bases (greaseless bases) - soften to a great extent with addition of water, so large amounts of aqueous solutions cannot be incorporated effectively; used for incorporation of solid substances
What disadvantages are associated with oral solutions?
- dose inaccuracy
- unpleasant taste
- inconvenient to transport and store
- instability
- microbial contamination
_______ is a process of size enlargement where small particles are converted into larger aggregates.
Granulation
When preparing an emulsion, which phase (oil or water) is added to the other while mixing?
Water is added to the oil phase
Give examples of powders that come in bulk form as well as unit-dose-packages.
Bulk: antacids, laxatives, B-complex vitamins, and other nutritional substances
Bulk powders intended for external use should be an external use only sticker. Dispensing powder medication in bulk quantity should be limited to non-potent substances.
Substances that need controlled dosage administration must be in divided powder packets (potent substances)
____ are flavored medicated dosage forms intended to be sucked and held in the mouth or pharynx, that contain 1-2 medications usually in a flavored sweetened base
Lozenges
Identify the purpose and examples of the excipient:
Chelating Agents
Purpose - chelates metal ions and prevents metal ions promoting oxidation
Example - EDTA
What types of particulate carriers are there?
- sphere: drug is absorbed or dispersed in nanometer or micrometer sized polymeric matrix
- capsule: particles are surrounded by a polymer; consists of a shell and a space in which the drug or any other substance is place
nanocarrier: nanocapsules and nanoparticles
If aerosol droplet velocity is greater than IFR, then droplets deposit in the _____
oropharyngeal region
Identify the purpose and examples of the excipient:
Glidant
Purpose - improves the flow properties of powder formulations in tablets or capsules by reducing inter-particle friction
Examples - colloidal silica, magnesium stearate
______ is partial or complete separation of the top or bottom of a tablet from the main body.
Capping
____ is the term that refers to the property of liquids to mix in all proportions, forming a homogenous mixture.
miscibility
______ are used for both liquid and dry powder formulations. What are they made of?
Vials
They’re made of glass or plastic and sealed with a rubber stopper
Identify the purpose and examples of the excipient:
Hydrophobic Solvents
Purpose - liquid with low or now miscibility with water; used to dissolve solutes
Examples - oils (canola, coconut) and fats
The two classes of aerosols are…
Compare them.
Space Spray
- produces airborne mist
- particles remain airborne for a long time
Surface Spray
- sprays active ingredients onto surfaces
Compare and contrast active and passive functional targeting.
Passive - exploits the natural distribution of the drug carrier in vivo; no homing device is used
- application: treatment of macrophage associated disease; Leishmaniasis; treatment of lysosomal enzyme deficiency
Active - has all 3 components (carrier, homing device, & drug); the homing device is attached ot the carrier or drug; molecules over-expressed in some diseases can be targeted
Which tablets release drug in a controlled (typically zero-order rate) manner?
Osmotically active tablets
Chewable (gummy) lozenges are based on ______ formulas that consiste of…
Another base could be _________
glycerinated gelatin formulas
consist of glycerin, gelatin, and water
gummy type candy such as gummy worms or gummy bears
Define the different classes of the BCS system of drugs. Which ones can you apply for a bioavailability waiver for?
Class 1 & Class 3 can get waivers
Class 1 - high solubility, high permeability
Class 2 - low solubility, high permeability
Class 3 - high solubility, low permeability
Class 4 - low solubility, low permeability
Identify the purpose and examples of the excipient:
Anti-foaming agent
Purpose - breaks and inhibits formation of foam
Example - Simethicone
Why are viscosity inducing agents added to solutions?
Give examples of viscosity inducing agents.
- to increase palatability of oral liquid
- to achieve desirable mouth feel
Methlycellulose, carboxymethlcellulose, hydroxypropyl cellulose, acacia (gum arabic), tragacanth gum, xanthan gum
List requirements of ophthalmic dosage forms.
- sterile (free from particles)
- buffered
- isotonic
- non-irritating
- non-greasy
- efficacious
Describe what is involved with antibody directed enzyme prodrug therapy (ADEPT).
It uses tumor cell specific surface ligands.
Conjugates an enzyme, which is not present in the extracellular fluid or on cell membranes, with an anti-tumor antibody.
The enzyme-antibody conjugate is administered first, which then goes on to locate the tumor. Then, a prodrug is administered after the conjugate is eliminated from circulation.
The tumors’ enzyme-antibody converts the prodrug to the cytotoxic partent compound at the tumor site.
Failure to coordinate actuation of _____ during the early phase of inspiration will make the particles deposit in the _____ region.
pMDI
oropharyngeal
What are potential mechanisms of clearance for undissolved particles in the lungs
cleared by mucociliary clearance mechanisms
phagocytosed by macrophages
an _________ is a solid dosage form that is placed into a naturally occuring (non-surgical) body cavity other than the mouth or rectum, which includes the ____________________.
insert
vagina and urethra
Aerodynamic diameter ______ with increases in density
Geometric diameter ______ with increases in density
Aerodynamic increases
Geometric decreases
The shape of the tablet is retained in the GIT in the case of
inert plastic matrix tablets
Identify the purpose and examples of the excipient:
Gelling (thickening) agent/stabilizer
Purpose - Increases the viscosity of the substance; can stabilize the mixture
Examples - gelatin, bentonite, Agar, alginates, guar gums, acacia, tragacanth, carbomer, cellulose, starches
Describe the advantages and disadvantages associated with lozenges.
Advantages: easy to administer to pediatric and geriatric patients; are easy to make and can be patient specific
Disadvantages: gummy type ones can be perceived as candy and not a real dosage form
when the gel consists of floccules of small distinct particles, it is called _________
two phase geles or magma or milk
MMAD stands for…
Mass median aerodynamic diameter.
What is lyophilization?
Freeze Drying
- many pharmaceuticals are unstable in solution
- lyophilization is a process in which the water is removed from the product using “sublimation”
- a vacuum is aplied to the frozen product so that water changes directly from solid to gas
Gels in which the macromolecules do NOT have apparent boundaries between them and the liquid are
single-phase gels
Why would you use film coating over sugar coating?
- Less coating time
- no more than 2-5% increase in weight as opposed to 50-100%
- can be used for pills and granules
- doesn’t require waterproofing
- more durable, flexible, and chip resistant
- monogramming is feasible because the coating is thin enough
______ is the separation of a tablet into 2 or more distinct layers
lamination
Which two key components govern the solubility of an organic solute in water?
1 - molecular structure
2 - cyrstal structure (melting point and enthalpy of fusion)
In what order does a solid dosage form break down
Disintegration –> Dissolution –> Absorption
What is meant by the term “enhanced permeability and retention effect”?
EPR is that clearance from tumor tissue is delayed due to poor lymphatic drainage
(blood vessels in tumors are leakier than those in normal tissue; this traps macromolecules and prevents their escape)
Describe how liposomes are classified.
Based on size and number of lamellae
- small unilamellar vesicles (SUV) are 20-100nm
- large unilamellar vesicles (LUV) are a few hunder nm to several micrometers
- large multilamellar vesciles (MLV) or multivesicular vesicles (MVV) are a few hundred nm to several microns
- the thickness of membrane measures about 5-6 nm
Nascobal is an example of a
Nasal gel
Why would glycerin, sorbitol, or propylene glycol be added to a gelatin capsule?
They all work to plasticize the shell, making the gelatin elastic which makes the capsules more soft (soft gelatin capsules)
Identify the purpose of sugar coating.
- protect against degradation from air and humidity
- masks bitter taste or bad smell
- prevents unwanted contact with the drug (ex. proscar should not be touched by pregnant women)
- enhances elegance and appearance
which new type of nasal drug delivery technology disrupts the natural airflow stream in the nose and disperses drug into the entire nasal cavity?
Kurve
Describe deposition by diffusion.
- Particles smaller than 0.1um are deposited by diffusion
- Ultrafine particles collide with gas molecules and change their kinetic energy and direction
- Increases with time
- Decreases with particle diameter
- Occurs in:
- Small airways
- Lung periphery
Autohaler is an example of
a breath actuated imhaler
_______ are clear, sweetened, hydroalcoholic solutions intended for oral use.
Elixirs
Elixirs that have high alcoholic content use artificial sweeteners such as saccharin rather than sucrose
Deposition in the first few generations of the respiratory tract ________ with increasing IFR (inspiratory flow rate)
increases
What is the BCS definition of rapidly dissolving?
an IR drug substance is considered rapidly dissolving when 85% or more of the labeled amount of drug substance dissolves within 30 minutes using USP apparatus 1 (basket) at 100 rpm or apparatus 2 (paddle) at 50 rpm in a volume of 500mL or less
Identify the purpose and examples of the excipient:
Enteric Coating Agent
Purpose - prevents the dosage form from getting destroyed by stomach acid
Examples - cellulose acetate phthalate, shellac
What are the limitations of the BCS?
Does not take into account the effects of uptake and efflux transporters and the route of elimination (disposition) that play important roles in drug absorption and bioavailability
Tablet compression involves the use of ___ punches and ____ die
2 punches (upper and lower) and 1 die
Steps:
- The lower punch falls and makes a cavity in the die for the material to entery the cavity
- The upper punch descends and enters the die, confining the particles
- The upper punch moves up from the die and the lower punch rises up to the level of the die top; the tablet ejects and goes to the collection chamber
Conventional tablets are prepared by
single compression and usually for immediate action
Large Volume Parenterals (LVPs) are generally administered via __________ as a means of…
Intravenous infusion
as a means of fluid replacement, electrolyte balance restoration, or for TPN
Fill in the corresponding “parts of solvent required for 1 part of solute” for each descriptive term:
- very soluble
- freely soluble
- soluble
- sparingly soluble
- slightly soluble
- very slightly soluble
- practically insoluble, or insoluble
- very soluble: < 1
- freely soluble: 1-10
- soluble: 10-30
- sparingly soluble: 30-100
- slightly soluble: 100-1000
- very slightly soluble: 1000-10,000
- practically insoluble, or insoluble: 10,000+
The shell of vegetable capsules is made up of
HMPC aka hydroxypropylmethylcellulose aka hypromellose
Describe deposition by sedimentation.
- Particles settle because of gravity
- Depend on the square of the particle diameter
- Varies with: time and density of the particles
- Occurs in:
- regions of maximum residence time of tidal air
- small airways
- lung periphery
When testing for content uniformity, the API in each label should be between ____ and ____% of the label claim.
85-115%
Identify the purpose and examples of the excipient:
Anti-adherent/Lubricant
Purpose - helps avoid particles sticking to each other and sticking to equipment during manufacturing (reduces friction), improves powder flowability
Example - magnesium stearate
AmBisome and DaunoXome are…
Commercial liposomes
AmBisome is unilamellar
Identify the two delivery devices under development that use bidirectional inhaler technology.
Directhaler
Optinose
List the types of air-jet nebulizers in order from least to most drug loss.
Least = dosimetric nebulizers (only produce aerosols during inhalation phase)
Middle = breath enhanced vented nebulizers (produce mists more in inhalation than exhalation phase)
Most = standard unvented nebulizers (constant output nebulizers, so nebulizes during both inhalation and exhalation phases)
How does the sizing for capsules work
Capsules frange from 000 (largest size) to 5 (smallest size)
The dissolution rate is expressed by an equation called the
Noyes-Whitney’s Equation
_______ are concentrated, aqueous preparations of a sugar or sugar-substitute.
Syrups
***note, high concentration sucrose syrups will prevent microbial growth due to the relative absence of water
in _______ (aka ______) DPIs, patients active that DPI by inhalation.
Deposition of drug into the lungs depends on…
passive (breath actuated)
the patient’s inspiratory airflow
Identify the type of liposome:
- antibody coated liposome with long-circulating properties
- antibodies are conjugated either on the surface of pegylated liposomes or with the PEG chain
Stealth Immunoliposomes
Ophthalmic preparations are specialized dosage forms designed to be:
- instilled onto the external surface of the eye (______)
- administered by injection inside (______)
- adjacent (______) to the eye
or
- _____________ as an opthalmic device
topical
intraocular
periocular
intraocularly implanted
The respiratory airways (peripheral airways/pulmonary region) are comprised of
respiratory bronchioles, alveolar ducts, and alveoli
Mucociliary clearance is faster in the _______ part of the nasal cavity.
Posterior
True or false: water soluble substances are added to alcohol soluble substances (not the reverse).
True
It is done this way to maintain the highest possible alcoholic strength at all times so that there is minimal separation of alcohol-soluble components
The ______ region is known as central or conducting airways
Tracheo-bronchial region
________ is an alginate based matrix tablet. At low pH sodium alginate converts to insoluble alginic acid and forms a gel layer that controls drug release.
______ is a mixture of rapid and extended-release coated beads.
_______ is a bead filled capsule for bedtime dosing thhat allows for 4-5 hours delay in drug release so that the drug is released when BP and HR peak in the morning.
Isoptin (Verapamil)
Verelan (Verapamil)
Verelan PM (Verapamil)
Glucotrol XL, Procardia XL, and Concerta are all examples of what type of drug delivery system
Push-Pull Osmotic System
- used to deliver poorly soluble drugs
- composed of 2 layers
- Push layer containing hydrophilic polymer and osmotic active agents
- Drug layer containing poorly soluble drug and osmotic polymers
- Upon ingestion, water enters the drug layer and the water soluble polymers expand the push layer; this pushes the drug out of the laser drilled hole
______ are compressed tablets that pass unchanged from the stomach to the intestine. How is that possible?
Enteric Coated Tablets
- they’re coated with polymers that resist dissolution and disruption in the stomach (they only dissolve at intestinal pH of 5-7, thus preventing stomach first pass metabolism)
Describe when you would use type 1 (rotating basket) and type 2 (paddle) dissolution apparatuses.
Type 1 - used for dissolution of tablets, capsules, suppositories, control release formulations, and floating dosage forms
Type 2 - used for both orally disintegrating tablets, chewable tablets, capsules, and controlled release productions
What method is employed to test for weight variation in tablets?
During production, you periodically collect sample tablets to inspect visually and weigh
Weigh 10 tablets of 4 separate batches and take the average
The average should be within +/- 5%
When is direct compression used?
Used for drugs that possess free flowing and cohesive properties
Fat soluble drugs release more readily from bases of __________ or ___________, both of which dissolve slowly in body fluids.
Water soluble drugs release well in ________ base.
Fat soluble drugs release well in PEG and glycerinated gelatin bases
Water soluble drugs release well in cocoa butter
What is the BCS definition of a highly permeable substance?
A drug substance is considered highly permeable when the extent of absorption is determined to be 85% or more of the administered dose in comparison to IV
Provide examples of drugs that use coated beads and granules.
Theo-Dur Sprinkle
Theophylline
Spanules
Benzedrine (amphetamine sulfate)
Combid
Hispril
Sequels
Artane
Identify the purpose and examples of the excipient:
Opaquing Agent
Purpose - protection from light
Example - titanium dioxide
List the components of aerosols
Product concentration (API, antioxidants, surface active agents, solvents etc.)
Propellants (a liquified gas that pushes the product out; the propellants can also be solvents)
What is the BCS definition of a highly soluble substance?
A drug substance is considered highly soluble when the highest dose strength of an immediate release drug is soluble in 250mL or less aqueous media over a pH range of 1 - 6.8
Suppositories can be prepared by which 3 methods
1 - fusion molding (common)
2 - compression (suitable for heat labile drugs)
3 - hand rolling and shaping
_________ are semisolid systems consisting of dispersions made up of small inorganic or large organic molecules enclosing and interpentrated by a liquid.
Gels
Identify the purpose and examples of the excipient:
Preservatives
Purpose - help prevent microbial growth
Examples - chlorhexidine, sodium benzoate, benzoic acid, benzalkonium chloride, thimerosal, EDTA, benzyl alcohol
The term powder in pharmacy is used to:
- describe the physical form of a material (finely divided particles)
- describe a type of pharmaceutical preparation, i.e. a medicated powder
Identify the types of nebulizers.
- Air-Jet: high velocity airstream dispersion
- relies on the venturi effect
- Ultrasonic: ultrasonic energy dispersion
Define aerosol.
An aerosol is any fine spray in the air
It’s a colloidal 2-phase system consisting of the finely divided condensed matter and a gaseous medium
The dispersed phase may be liquid, solid, or a combination of both.
Dissolution rates drive the absorption of _______ soluble drugs, making it the rate limiting step for drug absorption
poorly soluble
What types of dissolution apparatuses are available?
1 - Basket
2 - Paddle
3 - Reciprocating Cylinder
4 - Flow through cell
Identify what comprises the two layers of nasal mucosa.
Gel Layer (upper layer)
- sticky and thick
- traps particles
Sol Layer (lower layer)
- thin and watery
- washes the stems of the cilia
What is the purpose of multiple or layered tablets?
- dispense incompatible drugs
- drugs release in different time points
- just to look good
- color coding
Sustained release reduces dosing frequency by ____
2 fold
Shells of capsules are usually made from ______
Gelatin
The process of particle size reduction is called
comminution
Slugging and roller compaction are used for what method of tablet formation?
Dry granulation
What’s the difference between nanopharmaceutical and a nanomedicine?
NP - a drug product that uses nanocarriers as delivery vehicle
NM - science that deals with the use of nanocarrier based drug delivery or diagnostic or medical procedures
Identify the purpose and examples of the excipient:
Adsorbet
Purpose - to keep powders dry
Examples - magnesium oxide/carbonate and kaolin
Overall, particles with a diameter of ______ show efficient penetration into the lungs.
1-5 um
For pMDIs, the momentum of the aerosol depends on the ________ rather than the patient’s IFR.
Device
List and describe the “official types” of small volume parenterals.
[drug] injection - liquid prep
[drug] for injection - dry solids that (upon addition of suitable vehicles) yield solutions
[drug] injectable emulsion - liquid prep of drug that’s dissolved/dispersed in a suitable emulsion medium
[drug] injectable suspension - liquid prep of solids suspended in suitable liquid medium
[drug] for injectable suspension - dry solids that (upon addition of suitable vehicles) yield suspensions
When is a preservative required for parenterals?
When can antimicrobial agents NOT be used (for serious)?
In all multi-dose parenterals
Not used in LVP or preservative free preps and some cannot be used in pediatric/neonatal formulations at all (alcohol, benzyl alcohol, and propylene glycol)
Identify the purpose and examples of the excipient:
Suppository bases
Purpose - used as base in preparing suppository
Examples - cocoa butter, hydrogenated vegetable oils (palm, coconut), glycerinated gelatin, PEG polymers
Micron size capsules that envelope solids, liquids, or gases
Microencapsulation
The 3 major components of pMDIs are
- Container
- Metering valve
- Spray actuator
Describe the preparation of liposomes.
- dissolve lipids in organic solvent (chloroform, or that + mixture)
- mix lipids with solvent
- use dry nitrogen or rotary evaporator to remove solvent & produce film
- evaporate residual solvent by placing on a vacuum pump
- dry film thoroughly
- film can be prepared by freeze drying
True or False: the cross sectional area of a single daughter branch is smaller than its mother branch.
True.
BUT - the SUM of the cross sectional area of the two daughter branches is LARGER than their mother’s. The cross sectional area increases with each order, the further from the mouth, the larger the area.
What are some benefits of drug targeting?
- deliver drugs to target cells/tissues (or even intracellular)
- keep drug out of non-target areas
- reduce leakage
- protect drug from metabolism
- reduce premature clearance
- retain the drug at site for desired time
- facilitate entry into cells
- biocompatible, biodegradable, and non-antigenic
Identify the purpose and examples of the excipient:
Emollient
Purpose - softens, smoothes the skin, and acts as a vehicle for drug delivery
Example - petroleum jelly
Fick’s first law states that
the rate of change in concentration (flux) is directly proportional to the concentration difference between the two sides of the diffusion layer.
_______ are semisolid preparations or emulsion systems that give a specific appearance due to the reflection of light; they have a soft, spreadable consistency
creams
Physical factors that affect particle deposition are
- Lung anatomy
- Oral vs. Nasal inhalation
- Inspiratory flow rate
- Co-ordination of aerosol generation and inspiration
- Tidal volume
- Disease states
_______ coating uses mechanical pans that produce glossy and convex tablets with a 50-100% increase in weight and size.
What coating materials can be used with this coating type?
Sugar coating
Polymer, SUGAR, wax
_______ is a unit-dose inhaler with drug in hard gelatin capsules
______ is a multi-dose inhaler with drug in foil blisters
_____ is a multi-dose inhaler with drug preloaded into the device
_____ is a reservoir type of device where hte dose is measured and delivered from the reservoir.
Handihaler
Diskhaler
Diskus
Clickhaler
When capsules are sealed by coating the gap between the cap and the body with a layer of gelatin, this is called
banding
The disadvantages to powdered dosage forms include
Patients may misunderstand the correct method of use
It is undesirable to take bitter or unpleasant tasting powders by oral administration
What are the parameters required for WFI?
What about for sterile water for injection?
And bacteriostatic water for injection?
- *WFI** (water for injection) - meets requirements for purified water (less than or equal to 100 CFU/mL)
- *sWFI**: made from WFI (water for injection) that has been sterilized (less than or equal to 10 CFU/100 mL) and packed in a single dose container of not greater than 1 liter in size (no antimicrobial agents/added substances)
- *B**: meets requirements for sWFI; contains 1+ antimicrobial agents (0.9% benzyl alcohol) when a preserved solution is desired; pack in pre-filled syringe/vial containing no more than 30mL; NOT used in LVP; NOT FOR USE IN NEONATES
For poorly soluble drugs (in the lungs), ______ is the rate limiting step for absorption
Dissolution
List the advantages of modified release tablets
- reduced total drug amount
- minimize drug accumulation with chronic dosing
- improve the speed or control of condition
- provide special effects
- reduce fluctuations in drug blood level
- cut dosing frequency
- enhance compliance
- reduce adverse side effects
- economy
Identify the purpose and examples of the excipient:
Disintegrant
Purpose - assists in breakup and distribution of contents from capsules/tablets (many mechanisms are attributed to the disintegrating action; most important of these is that disintegrants absorb water once inside the body and swell, due to which they disintegrate)
Examples - alginic acid, polacrillin potassium (Amberlite), various cellulose products, starches, compressed sugar (Nu-Tab)
What disadvantages are associated with suppositories?
- messy to apply
- variation of absorption based on
- colonic content, circulation route, pH
- if placement is too high it go through 1st pass metabolism
- GI problems (diarrhea)
- irritation for mucous caused by drugs or drug bases
- some suppositories “leak” or are expelled after insertion
- cultural/religious factors
- defecation may interrupt the absorption process if the drug is irritating
The forward section of the nose is the _______ and the 3 thin elevations behind it are the ________.
Vestibule
Turbinates
What types of opthalmic preparations are available?
- solutions (eye drops)
- suspensions
- ointments
- controlled release devices
- ocular inserts
- gels, gel-forming solutions
- intravitreal injections/implants
Three mechanisms of particle deposition are:
- Inertial impaction
- Sedimentation
- Diffusion
Why can’t some drugs be used for formulation of ophthalmic suspensions?
- if the drug is not sufficiently soluble, it cannot be formulated as a suspension
True or False: both water and lipid soluble drugs can be encapsulated into liposomes.
True
The velocity or rate of settling of sedimentation of suspended particles is expressed by the ________
Stokes Equation
True or false: hydrofluoro propellants are no longer used and chlorofluoro propellants are now used instead.
False, it’s the other way around
Compare and contrast the size range of nanoparticles and microparticles.
Nano = 5-1000 nm range
Micro = 3-1000 micrometer range
Define suppository.
solid dosage form intended for insertion into body orifices where it melts, softens, or dissolves and exerts localized or systemic effects
Identify the type of liposome:
- antibody ocnjugation does not ahve long-circulating properties
- are just conventional liposomes coated with antibodies
Non-stealth immunoliposomes
Spirits are alcoholic or hydro-alcoholic solutions of volatile or aromatic substances that are > ___% alcohol
60%
Lyophilized powders can be filled in a special type of prefilled syringe called a _____________.
Dual chambered syringe
Identify the type of liposome:
- made of only phospholipids, negatively or positively charged lipids, and or cholesterol
- readily taken up by phagocytic cells of reticuloendothelial system (RES) <– this is a limitation
- localized predominantly in liver and spleen
- are made of natural lipids
Conventional
