Busy. Please wait.

show password
Forgot Password?

Don't have an account?  Sign up 

Username is available taken
show password


Make sure to remember your password. If you forget it there is no way for StudyStack to send you a reset link. You would need to create a new account.

By signing up, I agree to StudyStack's Terms of Service and Privacy Policy.

Already a StudyStack user? Log In

Reset Password
Enter the associated with your account, and we'll email you a link to reset your password.

Remove ads
Don't know
remaining cards
To flip the current card, click it or press the Spacebar key.  To move the current card to one of the three colored boxes, click on the box.  You may also press the UP ARROW key to move the card to the "Know" box, the DOWN ARROW key to move the card to the "Don't know" box, or the RIGHT ARROW key to move the card to the Remaining box.  You may also click on the card displayed in any of the three boxes to bring that card back to the center.

Pass complete!

"Know" box contains:
Time elapsed:
restart all cards

Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.

  Normal Size     Small Size show me how

Drug Delivery Exam I

Modified Noyes-Whitney Equation dC/dt = kS (Csat-Ct) dissolution rate equation
crystalline form substances with definite identifiable shapes and it is chemically stable
amorphous form particle without definite shape and it is more soluble than crystalline but less stable and may have different biological activity
dissolution the process by which particle dissolve; before a drug can go thru absorption it must go thru this
diffusion layer it is a saturated drug layer around a particle when the drug molecules first enter into solution layer; the molecules from this layer will enter into solution and get absorbed thru body membrane then the layer is replenished from the particle
absorption process by which UNCHANGED drug moves from site of administration to site of measurement thru passive and carrier mediated transfer processes and the drug must be in soluble in solution and no in particle form
distribution a reversible transfer of drug from and to site of measurement
metabolism conversion of a drug into another chemical entity by a biochemical process
excretion irreversible loss of chemically UNCHANGED drug from the body
salt form of drugs their dissolution rate is higher than its parent acid or base drug form
biopharmaceutics the study of relationship b/w some of the physical & chemical properties of drug & its dosage form & biological effects observed important for bioavailability purpose: optimize biological response of drug product
disposition all processes that occur subsequent to absorption of the drug, so include DISTRIBUTION & ELIMINATION
elimination the loss of drug from the site of measurement include both METABOLISM & EXCRETION, sites include: liver (metabolism), kidney (urine), intestine (gut, feces), skin
First Pass Effect the loss of drug as it passes thru sites of elimination for the 1st time during the absorption process these sites include: liver, intestine, skin, NOT KIDNEY
intravascular placement of drug directly into blood IV or IA avoid first pass effect
extravascular placement of drug at a site that requires an absorption step to enter the blood stream PO, PR, SL, IM, SQ, etc
possible routes of drug administration oral Parenteral: IV, IM, IA, SC, etc respiratory & intranasal transdermal/topical ocular rectal vaginal, sublingual aural conjunctival
therapeutic range the range b/w minimum effective dose and maximum safety dose the narrower it is the more dangerous the drug
physiological factors affecting oral absorption pH of GI fluid (vary b/w ppl) perfusion permeability gastric emptying rate (vary by food) surface area for absorption metabolism (hepatic & extrahepatic)
different physiologic pH values gastric: fasted (<2-3); fed (4-5) Intestinal: varies regionally (5-7) colon: (7-7.5)
Factors that determine a Dosage Regiment the drug's toxicity & activity ADME patient's health factor therapy's ease factor others: DDI, tolerance etc
organic acid drugs those containing an ionizable carboxyl group (R-COOH)
organic base drugs those containing an ionizable amino group ( R-NH2, R2-NH, R3-N)
organic neutral drugs non-ionizable drugs
large drug molecule drugs that are polypeptide and proteins
passive transfer processes include passive diffusion and filtration
carrier mediated transfer processes include active transport, receptor mediated endocytosis
passive diffusion required lipid solubility (more nonpolar than polar group) ionization (organic acids/bases) increase polarity requires concentration gradient only nonionized form of a drug can diffuse across the lipid membrane
filtration depends on molecular size requires concentration gradient use channel protein
active transport 1) discrete transporter proteins, finite number, therefore saturable 2)structurally selective, competitive inhibition 3)require energy; can go against concentration gradient
receptor mediated endocytosis 1) involves membrane receptor 2) transport large polypeptides & proteins 3) likely to become increasingly important with the use of bio engineered proteins as drugs 4) forms an endosome around molecule to be transfer
acid drugs tend to be concentrate on the high pH (basic) side of the membrane
basic drugs tend to concentrate on the low pH side of the membrane
pKa the ionization tendency of the drug but it does not tell if the drug is acidic or basic pKa is the pH at which the drug is half ionized for each pH unit away from pKa, the ratio increases 10 fold pH has no effect on nonionizable drugs
alimentary tract route of administration 1) oral mucosa - rapid absorption, small surface area, used for potent drug to relieve anginal pain; avoid immediate exposure to liver 2) rectal mucosa - suppository for nauseated patients; 50% pass liver immediately
skin route administration few drugs can penetrate intact skin oily vehicle to enhance penetration CR topical patches
drug distribution drug concentration at the site of action determines the pharmacologic effect can be measured by examining blood or urine
apparent volume of distribution (Vd) volume the drug appears to be distributed in, at the same concentration as in blood: Vd = (amount drug in the body) / (concentration of drugs in the blood) show where the drug is, available for therapeutic manipulation large Vd = longer drug stays in b
distribution of drugs within the blood drug can be free in solution or bound to plasma proteins only free drugs can cross membrane to enter other tissues acidic drugs bind to albumin basic drugs bind to α1-acid glycoprotein only finite # of protein binding sites = saturation and competitio
distribution of drugs within the tissues lipophilic drugs are highly bounded, and tend to accumulate in adipose tissue basic drugs tend to move into cell due to lower pH in cell; they can accumulate in acidic intracellular organelles highly vascularized tissues tend to equilibrate [drug] fir
blood brain barrier tight junctions b/w endothelial cells of brain capillaries 1)passive diffusion - highly lipid soluble & polar drugs 2) active transport - for amino acid type drugs 3) endocytosis - engineered chimeric proteins
placental barrier all modes of transfer shown, but passive diffusion most important no protective barrier
biotransformation (drug metabolism) structural alternation of the drug molecue by action of various enzymes and general facilitates excretion of lipid soluble drugs by making them more water soluble it is biphasic metabolism (2 steps) oxidation and conjugation
Phase I biotransformation chemical modification of the drug & results in: 1)inactivation - detoxification 2)conversion of active drug to active drug metabolite 3) conversion of inactive drug to active - prodrug
Phase II biotransformation add conjugating group to drug molecule which almost always results in 1) pharmacological inactive metabolites 2) highly ionized, polar, water soluble metabolites exception: acetylation yields less soluble metabolites
presystemic/first-pass hepatic elimination when hepatic clearance sufficiently high enough to remove most of the drug from the blood passing thru the liver can be measure by extraction ratio: (Cin - Cout)/Cin hepatic clearance depends on activity of drug metabolizing enzymes & hepatic blood f
Liver microsomal metabolism microsomes are isolate smooth ER Smooth ER contains two important drug metabolizing enzyme systems: 1) cytochrome P-450 complex 2)UDP-glucuronyl transferase
Cytochrome P-450 (CYP) Complex iron-heme monoxygenase enzyme and NADPH-CYP oxidoreductase; needs molecular O2 and NADPH a lot of CYP ISOENZYMES wide range of substrates; each isoenzyme oxidize particular structural types exodogenous and endogenous metabolism
UDP-glucuronyl transferase forms glucuronic acid conjugates during drug metabolism
nonmicrosomal enzymes found in the liver, certain tissues, & plasma responsible for drug metabolism 1) phenolsulfotransferases - form sulfate conjugates 2) alcohol dehydrogenase 3) mitochondrial monoamines oxidase (MAO) 4) esterase 5) amidases
variability in biotransformation in different ppl 1) genetic differences in CYP isoenzymes; test with debrisoquin polymorphism test or gene chip tests 2) age differences: newborns are deficient in glucuronidation ability, elder's rate differ due to diff rate of deterioration 3)diff among individuals
variability in biotransformation among individuals 1)sex: females metabolize many drugs slower 2) pathology: liver disease 3) species differences 4) enzyme induction/inhibition due to other drug usage 5) enantiomers of drugs: Nexium is single enantiomer of Prilosec
cimetidine anti-ulcer inhibits the metabolism of warfarin
certain antifungal and antibiotics inhibit CYP3A4 which oxidizes terfenadine leading to excessive blood levels and arrhythmias
Fluoxetine (Prozac) inhibitor of microsomal oxiidation (CYP2D6)
grapefruit juice inhibits metabolism of cyclosporin
renal excretion of drugs 1)Glomerular iltration: only unbound (free) drug 2)Proximal tubular transport: secrete into urine; two systems, one for acid & base; competition (probenecid & penicillin to retain penicillin in body) 3)Distal tubule: reabsorption; use pH to vary results
Biliary Excretion of drugs 1)active transport of polar molecules, esp anionic (+ & -) into bile 2)the metabolites tend to be large molecules like glucuronicacid conjugates 3)enterohepatic recirculation
enterohepatic recirculation tends to prolong duration of drug; can be interrupted by diarrhea glucuronide conjugate reenter intestine with bile and turn back to free drug by bacterial glucuronidase
treatment of drug overdose 1)supportive treatment: treat patient not poison 2)antidotal: available for only few drugs 3)alter drug dispotion: slow absorptions 4)alter distribution: little can be done 5)alter biotransformation: slow down toxic metabolite 6)inc urine: diuresis &
powder intimate mixtures of dry, finely divdided drugs and/or chemicals that may be intended (oral powders) for internal or external (topical powders) use as a dosage form it is a mixture of powdered drugs and excipients (this dosage form has limited usage)
why powders API & excipient are in powder form topical powder or sterile powder in vial starting material for solid dosage (tap & cap), liquid dosage (reconstituion), semisolid dosage (oint & cream)
characterization for powder morphology purity solubility stability particle size & distribution uniformity compatibility in blends
common issues with powders dissolution rate suspension uniform distribution inhalation poor flow appearnace
characterize powder particle size sieve analysis: sieve # or mesh size 8 is very coarse, 80 is very fine granules are coarse to very coarse microscopy, sedimentation rate, light scattering, cascade impact (for inhalation
How to reduce particle size mortar & pestle, levigation, mills, pulverizer
how to blend powers blending: mixing powders to uniform by: spatulation, trituration, sifting, tumbling, geometric dilution
medicated powder oral powder for reconstitution: for ease to swallow & large dose, good for 2weeks, need to mask taste dry powder inhalation sterile dry powder: mix w/water for injection vaginal douche: mix with water, "external use only"
medicated powder application p.o. aerosol, suspension, injection, external usage
dusting powder powder in topical application common diluents: starch & talc sifter-top shaker container not a tight seal not for volatile/sensitive to moisture powder particles smaller than 45um minimize mechanical irritation (pass it thru 325 mesh sieve)
aerosols powder for inhalation >5um, 85% stay in upper respiratory 1-5um, 90% stay in alveolae <0.5um, exhale out
bulk powder, douche powders, topical powder, Brewer's yeast powder bulk powder: non potent powders douche powders: wash w/water, for vaginal use topical powder: anti-infective, antifungal Brewer's yeast powder: B complex vitmins
divided powder they are for unit dose or each use pack in powder paper and dispense in powder box as charts use waxed/glassine paper for moisture/air sensitive powder(volatile)
granules they are prepared agglomerates of powders; 4-12 sieve size; larger & more porous than powder; hydrophilic in nature due to pores starting material for tab & cap & suspension
granulation size enlargement process
why granules 1)goodflow 2)compressibility (use in cap & better bind when press) 3)uniformity (granules=API+excipient+binder) 4)for high-speed equipments 5)more stable in moisture & O2 6)less likely to cake in container 7)dissolution not affected/improved due to pores
granule's main composition active ingredient, binder, diluent, flavor, excipient, color
wet granulation use high shear granulator or fluid bed granulation 1)moist and mix powder to form lumps 2)wet lumps pass thru sieve 3)wet granules dry in oven/fluid bed dryer 4)dry granules pass thru sieve
Fluid Bed Granulation suspend power in air to mix and moisten. then dry in hot suspending air high inlet air temp=rapid evaporation of binder,small,griable granules low inlet air temp=longer drying,larger,denser,strong granules high feel rate=slow drying,large,dense,stron
dry granulation for drugs that are sensitive to water or heat roller compactor or slugging roller compactor method
dry granulation: slugging older process and slow mix with dry binder, compress into large cruge tab (slugs), mill to form granules
dry granulation: compaction powder blend compressed b/w roller to form a cake (ribbon), cake milled to granules
Created by: chinzcutie