Final Flashcards
What are the different types of capsules?
- Gelatin
- Methyl cellulose (HPMC) [best to use in DPI]
- Calcium alginate
- DRcaps™ Gastro Resistant Capsules
What are the steps for gelatin manufacturing?
- Derived from skin or bone
- Acid or alkali treatment
- Extended treatment periods
- Filter
- Vacuum concentration
- Cool to solidify
- Air dry
- Mill to size
How can capsules be closed?
- welded with heated metal pin
- bonded with molten gelatin
- snap fit
- coni-snap
Properties of soft gelatin capsules
- Shells of gelatin, glycerin or sorbitol added to induce plasticity
- Oblong, elliptical or spherical shape
- Used to encapsulate liquids, suspensions, pastes or dry powders
- Must be prepared filled and sealed in one continuous operation
What are the ways in which you can manufacture soft gelatin capsules?
- plate process
- die process
What does the die process consists of?
- a process which to manufacture soft gelatin capsules
- rotary process
- reciprocating process
What is the plate process?
- a process which to manufacture soft gelatin capsules
- molds
What types of formula is suitable for soft gelatin capsules?
- Water immiscible, volatile and nonvolatile liquids
- Oily, non-volatile liquids
- Not suitable for low molecular weight compounds that can easily pass through the capsule
What are the different types of coating for coated tablets?
- Sugar
- Film (make tablet more sturdy)
- Gelatin
- Enteric
What are the types of specialized tablets?
- chewable
- effervescent
- CR, ER
- sublingual
- buccal
What are the essential ingredients for tablets?
- diluent
- binder
- lubricant
Why would any ingredient be essential to tablets?
give the formula specific characteristics needed to be compressed
What are the ingredients to give tablets desirable characteristics?
- disintegrant
- color
- flavor
- sweetening agent
What is the purpose of a glidant?
- needed for formulations with poor flow
- not needed if lubricant is enough for flow
- improves flow characteristics of powder mixture
Define diluent
inert substance added to increase bulk to make a tablet of practical size for compression, or to adjust its size
What are examples of diluent?
- lactose
- calcium phosphate
- microcrystalline cellulose (Avicel®)
There needs to be a compatibility test between diluent and active ingredient. Give an example of an incompatibility.
Calcium salts interfering with absorption of tetracycline in the GI tract
How can a diluent affect bioavailability?
water soluble diluents can increase bioavailability of drugs that have low solubility; can enhance dissolution
Define binder
glues ingredients together and helps with compression; improves powder flow-ability
What are examples of binders?
- starch (10-20% paste)
- gelatin (10-20% solution)
- acacia
- CMC
- PVP
What is the purpose of a lubricant?
generally hydrophobic; to prevent adhesion of the powder formulation to the surfaces of the dice and punches of tableting machine; improves rate of flow of granulate; should be added after granulation
What are examples of lubricant?
- talc (1-5%)
- magnesium stearate
Why does talc undergo testing?
it may contain metals
What happens if you add too much lubricant?
- your tablet may become waterproof and it will affect wetting of the tablet
- lead to poor tablet disintegration
- poor dissolution
- decreased solubility
Give an example where talc needs to be purified.
if talc is not pure enough, it may have a high Ca concentration and will act as a decomposing agent towards ASA
What is an example of a glidant?
talc
Define disintegrant
substance or mixture of substances added to a tablet to facilitate its break-up or disintegration after oral ingestion
What are examples of distinegrants?
- starch
- celluloses
How can you tell the difference between the roles that starch plays?
- dilute/dissolve starch = binder
- mixed with diluent = used as disintegrant
- starch used as a binder usually has a lesser proportion
Why doesn’t effervescent tablets need disintegrants?
because the sodium bicarbonate, tartaric or citric acid effervescence will cause tablets to disintegrate
Which are the steps that we can add coloring agents and why?
- wet granulation: dissolved in binding solution prior to granulation
- dry granulation: blended in dry with other ingredients
What are examples of flavoring agents?
- Cyclamates and saccharine (banned)
- Aspartame
What does it mean when you have talc and magnesium stearate in the same compound?
one will act as the glidant and one will act as the lubricant
What are the purpose of tablet coating?
- cover unpleasant taste, odor, color
- physical and chemical protection
- DR or EC
- identification
- ease process of blistering
What are the different kinds of coatings?
- sugar coated
- film coated
- gelatin coated
- enteric coated
- compression coated
Purposes of sugar coating
- protection from air and humidity
- improve taste and smell
What can be used to waterproof tablets?
Shellac
What is used to smooth tablets?
dibasic calcium phosphate, titanium oxide, starch
Purposes of film coating
- improve presentation
- increase stability
- improve taste
What are examples of plasticizers and how are they used in tablets?
- used for film coating
- castor oil, diethyl phtalate, propylen glycol
What are examples of enteric coating materials?
- cellulose acetate phtalate
- poly(methacrylic acid-co-methyl-methacrylate)
- poly(vinyl acetate phtalate)
What are some commercially available for use enteric coating solutions?
- Aquateric®
- Caoteric®
- Eudragits™
Explain how enteric coating tablets allow the API to be released in the intestine instead of the stomach.
- At low pH, carboxyl groups remain protonated (not water soluble)
- At high pH, carboxyl group is ionized (becomes water soluble)
Describe ingredients in sublingual tablets
lactose or mannitol and saccharine is massed with 60% ethanol
What are ingredients in buccal tablets?
- lactose or mannitol
- HPMC
- silica gel
With respect to the film theory, what is a stagnant film?
a layer of solution which is saturated with the drug
Define sink condition
one-third times that of the maximum solubility of the drug
What are factors that influence dissolution from solid dosage forms?
- dosage form
- solubility
- dissolution media
- partition coefficient
- diffusivity
- diffusional path thickness
What are three interaction forces that occur in powder samples?
- capillary forces
- mechanical interlocking
- electrostatic charges
What are the main reasons to granulate pharmaceutical powders?
- make particle size more uniform
- improve powder flow
- improve compression characteristics of the drug
- densify materials
What are examples of plasticizers and how are they used in soft gelatin capsules?
- used to soften gelatin and make it more maleable
- sorbitol, glycerin
What are the ways in which tablets can disintegrate?
- wicking: disintegrant forms pored and water enters the pores which reduces the physical bonding forces between powder particles
- swelling: disintegrant particles swell inside tablet breaking the tablet from the inside
What are the advantages of a film coating over sugar coating?
- simpler process
- less ingredients in coating solution
- can provide thinner coats
Causes of capping / lamination
- insufficient binder
- undermixing of tablets ingredients
- fast speed of compression
Causes of sticking / picking
- insufficient amount of lubricant
- improper application of coating or insufficient drying time
Causes of erosion / chipping
- tablets are friable
- fast pan rotation during coating
- poor choice of plasticizer
Causes of bridging
- high viscosity of solid content in coating solution
- improper atomization pressure
- insufficient drying time
- slow pan rotation during coating
What are different types of media for dissolution?
- water
- solution with buffer
- simulated gastric fluid (SGF)
- simulated intestinal fluid (SIF)
What does SGF consists of?
- 0.2% NaCl in 0.7% HCl
- pepsin
What does SIF consists of?
- Phosphate buffer, pH=6.8
- pancreatin
Apparatus 1
- rotating basket
- less than 4h dissolution test
- standard volume 900-1000mL (also 1, 2, and 4L)
used for - tablets coated, IR, DR, EC
- capsules
- beads
- suppositories
- floating dosage forms
Apparatus 2
- paddle
- makes up about 80% of dissolution tests performed
- less than 4h dissolution test
- standard volume 900-1000mL
used for - tablets coated, IR, DR, EC
- capsules
- beads
- floating dosage form
Apparatus 3
- reciprocating cylinder
- 4-12h dissolution test
- standard volume 200-250mL
used for - controlled release tablets & beads
Apparatus 4
- flow-through cell
- designed for poorly soluble compounds
- flow rate: 10-100mL/min
used for - low solubility drugs
- microparticles
- implants
- suppositories
- controlled release formulations
Advantages and disadvantages to Apparatus 4
- Advantages: easy to change pH, pH profile, sink conditions maintained at all times, open and closed system, can be automated
- Disadvantages: de-aeration necessary, high volumes of media needed
Apparatus 5
- paddle over disk
- standard volume = 900m L
- used for transdermal patches
What should the time period be for an IR tablet to be dissolved?
15 - 60 minutes
What are the sizes of particles that get stuck in to nasopharyngeal region?
10-30 microm
What are the sizes of particles that get stuck in to bronchiolar region?
5-10 microm
What are the sizes of particles that get stuck in to alveolar region?
1-5 microm
What are local advantages of nasal drug delivery?
- Ease of administration
- Rapid absorption and onset of action
- Reduction in systemic side effects
What are systemic advantages of nasal drug delivery?
- Rich vasculature underlining the nasal mucosa
- does not undergo first pass metabolism
- Rate and extent of absorption similar to IV (for some drugs)
Disadvantages of nasal delivery
- Small site for absorption
- Mucociliary clearance
- Potentially short residence time
- Efficiency of delivery is important
What does formulation enhancers do to the drug?
- increase absorption
- increase time spent in cavity via mucoadhesives
What happens with chronic use of formulation enhancers for nasal routes?
nasal irritation
What are the types of dosage forms for nasal delivery?
- solution: drops, spray pump
- suspension sprays
- gels
- emulsions and ointments
- DPI
Factors that affect drug absorption
- size of drug molecule
- partition coefficient (lipid solubility)
- drug concentration
- ionization state of drug
- pH of absorption site
- vehicle for drug delivery
- mucosal contact time
What are the types of solubilizers or co-solvents for nasal dosage form?
– Alcohol, 200 proof (2%)
– Propylene glycol (20%)
What are surfactants used for in nasal dosage form?
to reduce surface tension for drug to penetrate membrane
What are tonicity agents used for in nasal dosage form?
so that tonicity in the nasal membrane is isotonic so it doesn’t get damaged
What is a popular bioadhesive?
chitosan
What are types of local action which nasal formulations can target?
- rhinitis
- nasal pruritus
- sinusitis
- runny nose (rhinorrhea)
- prevent polyps
What are types of systemic advantages which nasal formulations can achieve?
- convenient
- more efficient dose/effect (propanolol)
- avoid first pass metabolism
What are the effects of nasal route to the brain?
- bypasses BBB
- delivered via neural pathways
- minimize systemic exposure
Describe the size requirements for delivery to brain from nasal route.
make sure the droplet sizes are on the lower side (10 micron) so that it’s more sensitive to the upper concha to go to the brain
Define aerosol
dispersion of particles or droplets suspended in a gas or vapor
What are advantages of local delivery with respect to pulmonary route?
- can treat asthma, COPD
- rapid onset
- no interactions with food
- more acceptable then injections
What are advantages of systemic delivery with respect to pulmonary route?
- avoids first pass metabolism
- large surface area: (120 – 160 m2, ~ tennis court)
What are limitations of pulmonary route?
- lungs designed to prevent inhalation of exogenous compounds / particulates
- oropharyngeal irritation, taste
Define aerodynamic diameter
“How well the droplet or particle can fly in a stream of air”
What are the types of aerosol deposition?
- for >5 microm: electrostatic attraction, interception, impaction
- for <5 microm: gravitational settling (sedimentation), brownian diffusion
What is the purpose of holding your breath when inhaling an aerosol?
- no air exchange to decrease air velocity going down
- droplets fall down deeper
- enhancing sedimentation of aerosol
What is the preferred value of Geometric Standard Deviation (GSD) for particle size for inhalation? And what does this mean?
2; means that 95.5% of particles are at the site of action
How do you measure diameter of particles?
- individual free particle
- aggregation will act like a larger particle
- droplets which have free particles, particles will assume their free diameter inside the droplet
What is the important of density influencing deposition?
if a particle is larger in diameter but less in density, it can still act as if it is a small particle
What can hygroscopic particles do?
can absorb humidity in resp. tract and assume a larger diameter than intended
What are two conditions (that we talked about in class) that can be treated by nebulization?
- cystic fibrosis
- emphysema
What are types of nebulizers?
- air jet (makes up majority)
- ultrasonic
What are advantages of nebulizers?
- Aqueous solutions: no environmental concerns
- Does not depend on patient inspiratory force
What are disadvantages of nebulizers?
- Bulky / Not portable
- Equipment is not cheap
- Device designed independent of drugs; can lead to waste
- Contamination of device
With respect to nebulizers, what does droplet size depend on?
- volume of solution
- surface tension
- density and viscosity
- nebulizer equipment
Describe the events that take place in an ultrasonic nebulizer
- Energy generated to piezoelectric transducer
- Shakes to coupling fluid which goes to drug solution
- Droplets are formed
Advantages of ultrasonic nebulizer
can created smaller particles
Disadvantages of ultrasonic nebulizer
- complex apparatus
- cannot be used by particles degraded by heat
- not easily cleaned
Characteristics of solutions used for inhalation
- pH close to neutral
- iso-osmotic
- isotonic (if not, can cause vasoconstr.)
What is an example of advancements in nebulizers?
- AKITA JET used in Germany to treat CF
- tracks doses taken and doses missed
What are classes of drugs that can be used to treat asthma?
– Beta2-adrenergic agonists
– Glucocorticoids
– Mast cell stabilizer
Define MDI
Devices that contain a pressurized formulation that is aerosolized through an atomization nozzle; doses are metered
Advantages of MDI
- portable
- easy to use and convenient
- drug is protected from light, O2, and water
- tamper proof
Disdvantages of MDI
- enpensive
- prone to incorrect use
- pressurized contents
Specific to MDI, particle size released from MDI depends on what?
- formulation
- valve design
- actuator
- propellant
What are the uses for propellants in MDI’s?
– Provide pressure to expel product
– Also act as dispersion medium
– Occasionally exhibit solvent properties
What are the uses for solvents in MDI’s?
– Bring active ingredient into solution
– Co-solvent for immiscible liquids
– influence particle size
– reduce vapor pressure
What is the Montreal Protocol?
- CFC [Chlorofluorocarbons] were killing the ozone layer; mandate to stop using it
- HFA [Hydrofluoroalkanes] used in its place and transition all to HFA by 2005
What effect does vapor pressure have on formulation performance in MDI’s?
- particle size
- droplet evaporation
- velocity
Advantages of DPI
- does not require coordination with actuation (but do breathe in with full force)
- don’t have to worry about solubility
- less likely that microbe will grow in powder
- can deliver higher doses
- tamper proof
Disadvantages of DPI
- breathe in with full force (not recommended for children or elderly)
- strength of pt’s airflow determines dose administered
- active DPI may be expensive
Sedimentation that occurs between bronchiolar and alveolar region has to be what size?
3-5 microm
Diffusion occurs where and what size does it have to be?
alveolar region at <1 microm
What are the major components of an MDI?
- canister
- valve
- actuator
What are five symptoms / diseases that nasal formulations can be used for?
- seasonal allergies
- pain
- migraine
- smoking cessation aids
- influenza vaccine
What are humectants used for in nasal products?
to avoid dryness of nasal cavity while using medication
What are solubilizers used for in nasal products?
to increase the concentrations of drugs that have poor aqueous solubility
How do you apply semi-solid preparations?
topically
What are examples of non-medicated semi-solid preparations?
- emollient (moisturizer)
- skin protectant
What are the classifications of bases for semi-solids?
- oleaginous
- absorption
- water removable
- greaseless
other names for oleaginous bases
- hydrocarbon bases
- hydrophobic bases
oleaginous base properties
- highest occlusion properties
- most oily
- difficult to wash off skin
- difficult to incorporate aqueous agents
- immiscible with water
- used to protect skin and emollient effects
examples of oleaginous bases
- regular and white petrolatum
- yellow and white ointment
absorption base properties
- able to absorb aqueous solutions to give w/o emulsion
- used for emollient effects
- difficult to wash off skin
examples of absorption bases
- hydrophilic petrolatum
- lanolin (wool fat)
water removable base properties
- also known as water washable
- external phase has to be water; o/w phase
example of water removable bases
hydrophilic ointment
greaseless base properties
- water soluble
- good for incorporating solid compounds
- soften with addition of water
example of greaseless bases
PEG ointment
What does PEG stand for and what are its other names?
- Polyethylene glycol
- PEO (polyethylene oxide)
- POE (polyoxy ethylene)
What are the ways in which you can prepare ointments?
- incorporation method
- fusion method (melt)
What materials can you use for the incorporation method?
- pill tile
- parchment paper
- unguator
- mortar and pestle
What is an unguator?
- electronic mortar and pestle
- equipment that goes inside the ointment jar an into the machine consists of a shaft and a blade
Define levigation
triturating a powder in an insoluble solvent
What are examples of levigating agents?
- mineral oil for oil phases
- glycerin for water phases
What are the steps to the incorporation method?
- incorporate drug into absorption base
- incorporate absorption base into oleaginous base
What is one thing to note when mixing ingredients in the fusion method?
mix the excipients with the highest melting point first
What are products that you HAVE to use fusion method for?
- beeswax
- paraffin
- stearyl alcohol
- PEG with high molecular weight