Exam 3 Flashcards
Which administration routes make up about 90% of them?
oral, pulmonary, transdermal, parenteral
What are the advantages of tablets and capsules?
- stability
- accurate dose
- patient compliance
- low cost
- additional functions such as taste masking or controlled release
What are the disadvantages for tablets and capsules?
- not suitable for infants and children
- not suitable for non-oral medications
What are the advantages to IV solution?
- fast drug action
- suitable for drugs that can’t tolerate GI tract environment
- suitable for patients who are unable to swallow tablets or capsules
What are the disadvantages to IV solution?
- expensive
- not convenient
- pain
What are transdermal patches good for?
local treatment
What kind of drug do transdermal patches require?
potent
What are the advantages to intranasal sprays?
- mostly used for local treatment
- can also be used for systemic drug delivery
What are the factors that dictate route of administration?
- disease state treated
- convenience to patients
- marketing
List the types of solid dosage forms.
tablets, gelcaps, loose powders, lyophilized powders, controlled-release matrices
What makes liqui-gels different?
- the drug is pre-dissolved
- drug will still precipitate in stomach
- has to re-dissolve
What are the two types of tablets?
compression, molded
Describe compression tablets
- dominant
- formed by compression
- may or may not have coating
How are molded tablets formed?
melting
What does the multicoat of a sugar-coated tablet contain?
starch, calcium carbonate
What percent weight does a sugar-coating add?
50%
What percent weight does a film-coated tablet add?
2-6%
What are the advantages to sugar-coated tablets?
- taste masking and/or identification
- might enhance stability from oxidation
What are the advantages of film-coated tablets?
- can avoid using moisture/water
- put marking on tablets
Describe multiple compression tablets
- have inner core and coating
- inner core could be sugar tablet
Describe multiple layer tablets
- lightly compress one layer
- additional layers added
- can put additional layers if needed to separate drugs
- can be used for multiple types of release
Characteristics of enteric-coated tablets
- resist dissolving in stomach
- dissolve at higher pH
- used for drugs that can irritate the stomach
- cannot be crushed or chewed
What are 3 examples of enteric-coated tablets?
aspirin, omeprazole, sulfasalazine
Describe chewable tablets
- large tablets designed to be chewed before being swallowed
- may not need water
- may help solubility
- avoids swallowing issues
- no disintegrant
What are the common fillers for chewable tablets?
sorbitol, mannitol
What is an example of a chewable tablet?
singulair (montelukast)
How are effervescent tablets administered?
- dissolved in glass of water prior to administration
What is the benefit of effervescent tablets releasing carbon dioxide?
- aids in disintegration/dissolution
- creates a buffered solution with high pH
What are the benefits to the fast action of effervescent tablets?
- faster bioavailability
- less gastric irritation
What do effervescent tablets need to be protected from?
moisture
What type of capsule is commonly used for compounding?
hard gelatin
What are hard and soft gelatin capsules made out of?
collagen
Which kind of capsule uses two ribbons for manufacturing?
soft gelatin
What are the characteristics of solution?
- faster to act
- less stable
- more for parenteral administration
What are the characteristics of solid state?
- slower to act
- more stable
- more convenient
- common for oral admin
preformulation
determining the physicochemical properties necessary to formulate the compound
formulation
determining the route and composition of the final dosage form
Most organics have a relatively low solubility, unless they are ________.
salts
What are the three states of solubility?
completely soluble, supersaturated, very supersaturated (labile)
What will high levels of supersaturation result it?
crystallization
Which is more reactive: crystal lattice or amorphous?
amorphous
What are reactions dictated by?
availability of reactant
Why can’t you administer only the drug substance?
- unstable
- needs taste masking
- hard to administer
What are some of the roles of excipients?
- preservative
- solubility enhancer
- stability enhancer
- taste masking
List the types of excipients
diluents, disintegrants, binders, lubricants, glidants, controlled release
diluents
- referred to as bulking agents
- needed to make practical weight for tablet
- compression aid
- enhances powder flow for manufacturing
Examples of diluents
- microcrystalline cellulose, lactose, calcium phosphate dibasic dihydrate, starch, compressible sugar
Disintegrants
- breaks up solid dosage forms, enhancing dissolution
- works by either water uptake and/or swelling
disintegrant examples
sodium starch glycolate, croscarmellose sodium, crospovidone, starch
binders
- give tablets mechanical strength, creates granules in wet milling
- works by either water uptake and/or swelling
binder examples
polyvinylpyrrolidone, starch, mircrocrystalline cellulose, polymers
lubricants
- prevents adherence of tablet to the die after compaction
- overlubrication can affect dissolution
- used at levels of 0.5% - 2%
lubricant examples
magnesium stearate (most common), stearic acid, lubritab, talc
glidants
- improves powder flow
- stops inter-particle friction
- used at levels of <0.2%
- low bulk density – fluffy
- can have problems with asbestos (talc)
gildants examples
fumed silica, talc
controlled release
used to extend the release of drug from a matrix
controlled release example
HPMC, hyromellose, xantham gum
Roles of coloring agents
- improves esthetics
- identification to user
- control product
- help in case of poisoning
What properties do we need to know while formulating a dosage form?
- physical and chemical properties
- mechanical properties
- biopharmaceutical properties
A drug needs to be _________
stable, bioavailable, deliverable
Aqueous solubility
- concentration at which the solution is in equilibrium with the solid phase
- depends on temp, pressure
- key to bioavailability
dissolution rate
- determines how quickly it goes into solution
- might be enhanced by fast-dissolving tablets
- important for in vivo- in vitro correlation
- measured using simulated gastric fluid
ionization constant
- affects dissolution, membrane partition, complexation, chemical stability, absorption
- protonated or non-protonated
polymorphism
- molecules may have multiple crystalline forms
amorphous
- lack of long-range order
- usually has higher solubility than crystalline form of drug
- unstable - wants to crystallize
- enhanced bioavailability – good for poorly-soluble drugs
hydroscopicity
- amount of water taken up by solid
- significantly affects stability and manufacturability
- water uptake can be used to measure surface area and disordered/high energy sites
types of deformation
elastic, plastic, brittle fracture
elastic
material deforms and then returns to equilibrium – reversible
plastic
material deforms beyond elastic deformation – irreversible
brittle fracture
material breaks into smaller fragments
Goal of manufacturing
take API and turn it into a dosage form that is stable, soluble, and easy to administer
unit operations
weighing, blending/mixing, milling, granulation, drying, compaction (tableting), coating, packaging
modified release
one in which the time course, location of drug release, or both, are altered to accomplish therapeutic objectives not achieved by conventional dosage forms
zero-order
releases drug at a constant and known rate
variable release
releases drug at a variable rates so as to match circadian rhythms
- useful when changes in blood concentrations are necessary
bio-responsive
drug release triggered by a change in biological stimulus such as pH, temperature, or concentration of some disease marker
Which modified release systems are practical?
delayed-release, extended-release
delayed-release delivery system
one that releases a drug all at once but at a time other than promptly after administration – often bioresponsive
extended-release delivery system
achieves slow release over extended period of time
What are two reasons to employ delayed-release?
- avoid release in stomach
- chronotherapy
chronotherapy
timing of drug release to be in harmony with biological rhythm of a disease
What strategies can be used to avoid stomach pH?
- change the pH
- avoid dissolution in stomach
What size of doses have greater variation in peaks and valleys?
high dose
How do you achieve constant blood level?
zero order
reservoir device
core of drug surrounded by a poorly water-soluble polymeric membrane
- diffusion of drug through membrane is rate-limiting step.
matrix device
dissolved or dispersed drug is uniformly throughout a polymer matrix
- diffusion through the matrix is rate-limiting step
flux
mass of drug that moves through a membrane per unit time
- Fick’s law
How are zero-order release kinetics attained?
- excess solid encapsulated makes this possible
- C1 high and constant
- C2 low and constant
- all other factors constant, so Flux must be constant
