Exam 3 Spring 2017 Flashcards
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
Define complexation
interaction between two or more compounds to form a complex
What is the center of a complex called?
- central atom / ion
- substrate
- acceptor atom
What is the name of the molecules attached to the central atom?
ligand
What is a coordination number of a complex?
it denotes the number of attachments to the central atom
What are pharmaceutical relevance to complexation?
- increased solubility
- increased drug stability
- aids in drug delivery system
- increase excretion of compound in urine
What are disadvantages to complexation?
- modify pharmacologic activity of drug
- decreased solubility
Classes of antacids
- neutralize acids
- H2 antagonist (block secretion of acids from parietal cells)
- proton pump inhibitor
Which drugs can antacids cannot be used with? (specific examples discussed in class)
- digoxin
- phenytoin
- chlorpromazine
Characteristics of transition metals
- open d orbital
- usually more than one oxidation state
- show characteristic colors
T/F; Metal ion complexes must always have a metal as the central atom.
False; it usually is metal but doesn’t have to be
Define capacity of binding
number of ligand binding sites in the protein molecule
What are properties that might change after formation of a complex?
- solubility
- stability
- partitioning
- energy absorption
- emission
- conductance of complex
Characteristics of inorganic complex
coordinate covalent link between ligand and central atom
Characteristics of chelated complex
- one or more ligand combine with central atom to form many bonds
- ligands are polydentated
Examples of inorganic complexes
silver-ammonia complex, [Ag(NH3)2]+
Examples of chelates
Chlorophyll, hemoglobin, myoglobin and cytochrome c
Characteristics of organic molecular complex
- substrate-ligand held together by weak forces
- small + small or small + large molecules
Examples of organic molecular complexes
theophylline to form aminophylline; polymer complex
Examples of polymer complexes
PEG, polystyrene, carboxymethylcellulose
Characteristics of cyclodextrin complex
- donut-shaped cyclic structure of glucose moeities
What is the diameter of the cyclodextrin cavity?
5 to 8 Å
Characteristics of channel lattices
- crystals of deoxycholic acid (DCA) are arranged to form a channel
- camphor and terpinol bind within the lattice structure of DCA to produce an inclusion complex
What can channel lattices form complexes with?
- paraffins
- organic acids
- aromatic compounds
Examples of layer type complex
bentonite can trap hydrocarbons and glycols between the layers of their lattices
Characteristics of clathrates
cage like lattic
Examples of clathrates
warfarin sodium USP, is a clathrate of water, isopropyl alcohol, and sodium warfarin in the form of crystalline powder
Characteristics of albumin
- most important plasma protein
- MW of ~65 KDa
- bind to acidic (anionic) drugs
- synthesized in liver
What are the causes of hypoalbuminemia?
- cirrhosis of the liver
- viral hepatitis
- renal failure
- surgery
- burns
What are the causes of hyperalbuminemia?
- dehydration
- certain neurological disorders
What can affect the affinity of a drug towards albumin, AAG, and lipoprotein?
- presence of another drug
- disease condition
Characteristics of AAG
- α1 -Acid Glycoprotein
- lower concentration than albumin
- MW of ~44 KDa
- binds to basic (cationic) and neutral drugs
- synthesized in liver
Examples of acidic (anionic) drugs
- phenytoin
- tolbutamide
- warfarin
- naproxane
- ibuprofen
Examples of basic (cationic) drugs
- propranolol
- imipramine
- lidocaine
Characteristics of lipoproteins
- less than 0.5% concentration
- bind to basic and neutral drugs
- synthesized in liver AND intestinal mucosa
What are solubilizers used for in nasal products?
to increase the concentrations of drugs that have poor aqueous solubility
What are humectants used for in nasal products?
to avoid dryness of nasal cavity while using medication
What are five symptoms / diseases that nasal formulations can be used for?
- seasonal allergies
- pain
- migraine
- smoking cessation aids
- influenza vaccine
What are the major components of an MDI?
- canister
- valve
- actuator
