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