Exam 2 Spring 2017 Flashcards
What are other names for size reduction?
- comminution
- micronization
What are examples of small scale size reduction?
- mortar and pestle
- levigation (semi-solid dosage forms)
- ball milling
What are examples of large scale size reduction?
- hammer mill
- fitzmill
- airject mill (attrition)
Properties of ball milling
- batch process
- capacity of 100g to a few kg (maybe 5)
- reduces size to 50microm
What are factors that influence ball milling?
- # of balls
- rotation speed
- mass of powder
- length of milling time
Properties of hammer milling
- continuous process
- reduce size to 50microm
What are factors that influence hammer milling?
- feed rates
- milling speed
- screen size
Properties of Fitzmill
- like hammer mill
What are factors that influence Fitzmill?
- speed
Properties of air jet milling
- continuous process
- opposing air jets that operate at 100psig
- reduce particle size to 1-5microm (DPI)
What are factors that influence air jet milling?
- pressure
- velocity
What is another name for air jet milling?
attrition
What are the appropriate methods for different sizes particles?
- 1-40microm definitely air jet mill
- 40 and above, can use all the other techniques
The most common procedure for mixing is tumbling but there are some limitations to that. What are they?
- powder segregation
- sifting or percolation
- air entrapment (fluidization)
- particle entrapment (dusting)
What are the different types of blends?
- segregated mixture
- perfect mixture
- random mixture
What are the different types of mixers/blenders and what would you use them for?
- Dry ingredients: V-mixer, double cone, rotating cube
- Liquid ingredients: ribbon blender
What are the purposes of size enlargement?
- to make materials free-flowing
- to prepare uniform mixtures that don’t separate
- improve compression characteristics of the drug
- improve appearance of dosage form
What are the different size enlargement methods?
- dry granulation
- wet granulation
- spray drying
Describe dry granulation
- usually used when one of your ingredients may be composed of water (lec 2-6 @ 35:20)
- used for powders that are sensitive to moisture
- powder is condensed into a sheet or tablet-like block
Describe wet granulation
- used for moist powders
- spray powder with a liquid binder, liquid bridges formed, solid bridges formed, snowball structure formed
Describe spray drying
- droplets formed and compressed air comes together and forms particles, goes in a chamber where liquid is dried out
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
