Term
| What is the goal of drug delivery? |
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Definition
To:
Deliver the drug intact
In the right amount
At the right place
At the right time |
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Term
| Five Basic Medication Errors |
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Definition
Wrong Drug
Wrong Dose
Wrong Route
Wrong Time
Wrong Patient |
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Term
| Go through the flow of a drug in a person's body, starting with only the drug and inert additional substances? |
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Definition
| Drug+inert additional substances go into absorption into the body and "bio availability". This then goes into the distribution into compartments- then that goes to either metabolism or pharmalogical action. |
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Term
| What is are the problems of drugs? |
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Definition
Poor solubility
Tissue Damage on Extravasation
Rapid Breakdown of the drug in Vivo
unfavorable PK
Poor Biodistribution |
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Term
| What is an implication of poor solubility |
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Definition
| A convenient pharmaceutical format is difficult to achieve, as hydrophobic drugs may precipitate in aqueous media. Toxicities are associated with the use of excipients such as cremophor (the solubilizer for paclitaxel in Taxol) |
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Term
| What is the implication of tissue damage on extravasation |
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Definition
| Inadvertent extravasation of cytotoxic drugs that leads to tissue damage (example is tissue necrosis with free doxorubicin) |
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Term
| What is the implication of unfavorable Pk? |
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Definition
| This is when drug is cleared too rapidly, by the kidney, for example, requiring high doses or continuous infusion. |
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Term
| What is the implication of Poor biodistribution? |
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Definition
| The drugs that have widespread distribution in the body can affect normal tissues, resulting in dose-limiting side effects, such as cardiac toxicity of doxorubicin. |
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Term
| What are effects of DDS on poor solubility? |
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Definition
| DDS such as lipid micelles or liposomes provide both hydrophillic and hydrophobic environments and enhancing drug solubility |
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Term
| What are the effects of DDS on tissue damage on extravasation? |
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Definition
| Regulated drug release from the DDS can reduce or eliminate tissue damage on accidental extravasation |
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Term
| What are the effects of DDS on the rapid breakdown of the drug in vivo? |
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Definition
| DDS protects the drug from premature degradation and functions as a sustained release system. Lower doses of the drug are required. |
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Term
| What are the effects of DDS on unfavorable pharmacokinetics? |
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Definition
| DDS can substantially alter the PK of the drug and reduce the clearance. Rapid renal clearance of small molecules is avoided. |
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Term
| What are the effects of DDS on poor biodistribution? |
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Definition
| The particulate nature of DDS lowers the volume of distribution and helps to reduce side effects in sensitive, non-target tissues. |
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Term
| How can DDS can increase the drug concentrations in disease tissues such as tumors? |
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Definition
| This is done by the EPR effects. Ligand-mediated targeting of the DDS can further improve the drug specificity. |
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Term
| What are key considerations in drug delivery? |
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Definition
The drug "personality"
Dose/quantity/accuracy
drug bioavailability
drug stability
manufacturable
Product acceptance
+convenience
+ compliance
+acute/chronic |
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Term
| What are elements of Drug delivery? |
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Definition
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Term
| What is a drug "personality" |
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Definition
| Each drug has intrinsic chemical and physical characteristics that must be considered before the start of a formulation |
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Term
| What aspects are involved in a drug personality? |
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Definition
Solubility
partition coefficient
dissolution rate
physical form
stability |
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Term
| What are characteristics of excipients? |
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Definition
They promote manufacturablity
promote stability
Promote bioavailability
Promote accurate dosing
Promote patient acceptance and convenience
mostly inert
route?
Impact therapy? |
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Term
|
Definition
Immediate release of one dose
delayed release of one dose, then full release (enteric coated tablets)
Prolonged release of enough drug to increase intervals between dosing (once a day to once a year)
controlled release- spatial and temporal control |
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Term
| What are the major dosage forms? |
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Definition
*solids*
powders
capsules
tablets
implants
*Liquids*
solutions
suspensions
*semi-solids*
ointments
creams
suppositories |
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Term
| what is the pathway to get the best dissolution? |
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Definition
| Tablet disintegrates to granules which disintegrate to small particles and then goes to best dissolution. |
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Term
| What are systemic drug delivery? |
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Definition
*oral route*
*intravenous route*
*other routes*
IM or SC routes
transdermal route
sublingual or buccal routes
intranasal route
pulmonary route |
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Term
| Where are the local drug deliveries? |
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Definition
Skin
ears, eyes, nose, and throat
lungs
rectal, vaginal, and urethral routes
perfusion of organs- liver and brain |
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Term
| What are the major goals of local drug delivery? |
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Definition
minimum systemic absorption
optimal drug concentration reaches local site |
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Term
|
Definition
Disease and the drug
Access of the site of action
Retention, does it stay there
Timing of the drug |
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Term
|
Definition
polymeric drug or sequestrant
polymer-protein conjugate
polyplex polymer-DNA complex
polymer-drug conjugate
polymeric micelle |
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Term
| What are physiochemical propertices of drug influencing drug absorption? |
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Definition
*lipid solubility*
partition coefficient
*PKA*
henderson-hasselbach equation
*Molecular weight and volument*
stokes-einstein equation
*aqueous solubility*
dissolution rate limited
*chemical stability* |
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Term
|
Definition
molecular weight is greater than 500
log k (coctanol/c water) greater than 5
greater than 5 hydrogen bond donors
greater than 10 hydrogen bond acceptors |
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Term
| What are ways of carrier-mediated transport? |
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Definition
Involves a protein that spans a biological membran
active transport against a concentration gradient
facilitate diffusion with a concentration gradient
specificity saturation competition
the small intestine has a wide variety of transporters- AA, ogliopeptide, glucose and lactic acid
levodopa, methyldopa, and penicillamine are absorbed by AA transporters. |
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Term
| Give me characteristics of capillaries during trans-endothelial transport- extravasation? |
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Definition
*continuous: connective tissue, skin, muscle, and most other tissue in the body. serum albumin barely pass
*fenestrated: GI tract, glands, and renal glomerulus, endothelia have openings, fenestrae and clefts
sinusoidal- liver, spleen and bone marrow. Have cleffts of 100 nm and no basement membrane like the others
BBB- cells of these tight endothelium have few vesicles and their intercellular junctions are closed by belts in the tight junctions. |
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Term
| Give me characteristics of BBB during trans-endothelial transport- extravasation? |
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Definition
*lipophillic route through cell membrane
*carrier-mediated uptake
*carrier-mediated efflux
*drug efflux transporters operating in a luminal membrane, including PGP
*paracellular transport through hydrophllic pathway
*endocytosis and transcytosis via vesicular pathways. |
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Term
| definition of a dispersed system? |
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Definition
| in a pharm preparation- the particle distributed (ie undissolved or immiscible drug) is referred to as the dispersed phase and the vehicle is termed the disperising phase or dispersing medium. |
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Term
| What are the types of dispersions? |
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Definition
course dispersion- particle range in size from 10 to 50 micrometer (suspension and emulsions)
fine dispersions: particles range from 0.5 to 10 micrometers (gels)
colloidal dispersion: particles in the nanometer range |
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Term
| What are the three types of pharmaceutical mixture? |
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Definition
solutions
dispersions (powder blends)
dispersions (particles in liquid) |
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Term
| What are characteristics of solutions? |
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Definition
molecularly dispersed
spatially homogenous
thermodynamically stable (delta g=0) |
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Term
| What are the characteristics of power blend dispersions? |
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Definition
particles dispersed within other particles
they are not spatially homogenous
they are thermodynamically unstable (2 or more phases) |
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Term
| Dispersions of particles in a liquid, what are the 3 general physical instability problems? |
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Definition
nonwetting- solid particles don't disperse uniformly when placed into the liquid
aggregation/coalescence- particles aggregate to form larger agglomerates or, if liquid-liquid or vapor-liquid, they coalesce
sedimentation/creaming-particles (liquid, vapor, solid) sedmin or cream due to gravitational effects and density differences.
all these lead to a nonuniformity of particle dispersion within the liquid. |
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Term
| What are characteristics of liquid dispersions and give examples of pharmaceutical interest |
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Definition
particles dispersed in a liquid phase
they are not always spatially homogeneous
they are thermodynamically unstable (2 or more phases)
examples are suspension- solid in liquid
emulsions- liquid in liquid
forms- vapor in liquid |
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Term
| What are pharmaceutical uses of liquid dispersions? |
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Definition
suspensions- parenterally, orally, topically, ophthalmically, otically
emulsions- primarily topically, also prolonged release parenterals (vaccines)
foams: topically, rectally, vaginally |
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Term
| Advantages of suspensions relative to solutions? |
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Definition
They prolongs chemical stability of the drug
they can provide prolonged (sustained) release
Useful for administering less soluble drugs in convenient volumes (antibiotics administered orally, erythro ethylsuccinate) |
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Term
| Dispersion of powder particles in a liquid |
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Definition
involve mixing solids with liquids
particles will not mix uniformly with the liquid (we say that they are not "wetted"
float on the surface
agglomerate
stick to the container |
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Term
|
Definition
| surface tension= change in work/change in area |
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Term
| surface tension- highest is...? |
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Definition
| surface tension of water (72) |
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Term
| What is the nrgetic state of molecules at the surface relative to the bulk? |
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Definition
*unsatisfied valence forces are exposed @ surface resulting in higher nrg per molecule
*moelcules @ the surface respond by having fewer molecules per unit volume of surface than in the bulk phase
*molecules at the surface orient so as the reduce energetic differences with the another phase (vapor, liquid, or solid) |
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Term
| impact of surface tension on wettability of solids |
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Definition
solids and liquids with sufficiently similiar surface tensions will be compatible even if they do not dissolve "good wetting" (silica, sio2, in water)
*solids and liquids with very different durface tensions will not wet very well (teflon in water certain hydrophobic drugs and exicipients) |
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Term
| Less contact angle from solid and vapor, the better? |
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Definition
| yes, the better the wetting. |
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Term
| What is the equation relating work with overall free nrg? |
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Definition
delta G= surface tension*change in area
the higher the surface tension and area, the greater the work (more positive the free nrg) |
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Term
| The (bigger or smaller) the delta G, the better the extent of wetting? |
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Definition
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Term
| To promote wetting, which surface tensions must be high and which must be low? |
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Definition
| the lower the SL, the Lower LV, the higher the SV |
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Term
| How can be promote wetting? |
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Definition
coat the solid with other polar solids to raise the SV
use surface active agents to lower the LV and SL |
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Term
| What is the difference between surface tension and interfacial tension? |
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Definition
Surface tensions= f/l
this is used specifically to describe liquid-vapor and solid vapor systems
interfacial tension= f/l (broader)
mostly used to describe immiscible liquis-liquid, liquid-solid, solid-solid systems
strength of y is proportional to strength of intermolecular interactions in each phase |
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Term
| What does increasing the ratio for cos theta do to the angle? |
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Definition
| it decreases the angle (makes it closer to zero) |
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Term
| What is the young equation? |
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Definition
| Cos theta= (surface tension (SV)- Surface tension (sl))/surface tension (LV) |
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