Exam 1

Question 1

deliver a drug to the body at a predetermined rate, increase the duration of drug action and decrease the frequency of dosing (enhance compliance), reduce or eliminate adverse effects, provide a uniform constant plasma drug concentration, avoid the peaks and troughs for improved therapeutic outcome

Answer 1

why modified release formulations

Question 2

this drug is a rapid acting vasodilator, immediate release form causes significant and sudden reduction in BP, increased sympathetic outflow means increased HR and forcer contraction due to sudden drop, increase cardiac oxygen demand, if coronary blood flow does not increase than ischemia and necrosis can occur

Answer 2

why an immediate release form of nifedipine can potentially cause myocardial infarction

Question 3

what should be the release kinetics (first or zero order) to provide a constant plasma drug level?

Answer 3

Zero order (constant amount of drug, replacing what is eliminated by body so amount of drug in body is constant)

Question 4

to achieve a constant plasma drug level what should be the rate-limiting step (slowest step), drug release or drug absorption?

Answer 4

drug release, for a drug to be a good candidate its absorption should be fast because if slow is doesn’t matter if release is fast of slow because drug will just sit there

Question 5

1. dose-dumping (when modified dosage form releases all of its contents at once, everything gets released, contains more drug than immediate, can produce a high toxic level if chewed/released all at once)
2. mistakenly exchange immediate release formulations with modified release formulations or vice versa
3. less flexibility in dose adjustments (predetermined rate)
4. formulation challenges, not suitable for all drugs
5. problematic for patients with preexisting GI conditions for oral products like this (GI narrowing, shortened bowel, bariatric surgery)

Answer 5

limitations to modified release products

Question 6

what type of modified drug release is monolithic (meaning the whole tablet is uniform)?

Answer 6

matrix systems

Question 7

what type of modified drug release has different regions of the dosage form?

Answer 7

reservoir systems

Question 8

mechanism of drug release: dissolution or erosion of matrix
example is niacin extended release tablets (antilipemic agent), polygel controlled release delivery system

Answer 8

hydrophilic matrix: soluble

Question 9

patient counseling points:
- tablets come in 250mg, 500mg, 750mg scored, can be broken because monolithic but do not crush/chew
- long-acting forms reduce adverse effects of this drug including GI disorders, cough, skin rash, flushing
- tablets should be taken after a low-fat snack and cold water at bedtime because flushing will most likely occur during sleep
- also available in other dosage forms, should not substitute because they aren’t all the same

Answer 9

niacin ER tablets (Slo-Niacin)

Question 10

mechanism of drug release: swelling of the matrix (depends on how fast or slow the matrix swells), dissolution and diffusion of drug through swollen gel layer

Answer 10

hydrophilic matrix: swellable

Question 11

mechanism of drug release: dissolution and diffusion of drug through insoluble matrix
example: potassium chloride ER tablets (reduce the local adverse effect of KCl in GI tract

Answer 11

hydrophobic (insoluble) matrix

Question 12

tablets:
K-tab and Klor-Con (wax matrix tablets)
Klor-Con M10, M15, M20 (microencapsulated potassium chloride)
capsule:
generic comes in 8 or 10 mEq, sprinkles
Counseling points:
- oral dosage forms should be taken with meals and a full glass of water or other liquid to minimize the risk of GI irritation (ER tabs reduce likelihood of producing high localized concentrations of potassium in GIT)

Answer 12

potassium chloride ER products

Question 13

will draw in water, it will dissolve and create a channel, it is a water-soluble channeling agents, this affects drug release because increased this means increase channels for increased release rate

Answer 13

PEG

Question 14

what are tablets called that appear in the stool after administration because they have a wax layer on the outside (Klor-Con, not Klor-Con M because M has wax at a micro level so not big enough to see in stool)?

Answer 14

ghost tablets

Question 15

mechanism of drug release: drug dissolves out and then diffuses through a membrane (membrane still allows drug to come out, can’t break tabs because will release lots of drug at once)
example: felodipine ER coated tablet (calcium antagonist, rapid-acting vasodilator, lowers the risk of myocardial infarction)

Answer 15

reservoir system

Question 16

tablet core: matrix system
membrane coating: wax that creates membrane, PEG (pore forming agent)

Answer 16

Felodipine ER tabs

Question 17

what does OROS stand for?

Answer 17

osmotic-controlled release oral delivery system

Question 18

mechanism of drug release: solvent-activated push, very controlled laser drills hole that has to be same size every time, drug release ultimately depends on size of hole, zero order constant amount of drug, semipermeable but rigid membrane

Answer 18

OROS

Question 19

OROS example that should be swallowed whole, not crushed, split, or chewed

Answer 19

Procardia XL (nifedipine)

Question 20

which system is dose dumping more likely to occur with (matrix or reservoir)?

Answer 20

reservoir

Question 21

• dosage form that releases a discrete portion or portions of the drug at a time other than promptly after administration
• enteric coated dosage forms are an example of this (reduce stomach irritation like in aspirin, protect the drug from the acidic environment of the stomach like omeprazole, provide local action in the intestine/site of action like bisacodyl, prevent regurgitation and irritation of the esophagus like risedronate which is highly irritant)
• colon targeted drug delivery to treat problems in the colon, don’t want drug release in the stomach

Answer 21

delayed release dosage forms

Question 22

• coated microbeads, granules, pellets
• Coreg CR (carvedilol) ER capsule is for heart failure and hypertension, it’s like giving two doses one IR and one CR, capsules should not be crushed, chewed, or divided but contents of capsule can be sprinkled on applesauce for IR
• ConZip (tramadol) ER capsule - capsule has a tablet (IR) and beads (ER) inside it to provide this effect

Answer 22

repeat action - biphasic

Question 23

Concerta (methylphenidate) ER tablet for ADHD, elimination of this drug is about 3.5 hours (the IR tab is given every 4 hours/TID), OROS system, tablets should not be chewed, divided, crushed, ghost pill, drug overcoat gives first IR phase of release then inside is released in two phases

Answer 23

repeat action - triphasic

Question 24

Claritin D 12 or 24 hour: outer layer is IR with loratadine and pseudoephedrine, core is ER with just pseudoephedrine (core is larger because need more excipients for ER)

Answer 24

repeat action - multilayer tablets

Question 25

- drug release by this depends on pH of the stomach, properties of the resin, resins are water-insoluble - ER oral suspension hydrocodone polistirex and chlorpheniramine polistirex

Answer 25

ion exchange resin

Question 26

dose size, aqueous solubility, partition coefficient, drug stability, small molecules, high diffusivity

Answer 26

physiochemical properties of drug to consider for modified release dosage forms

Question 27

biological half-life, rate of absorption, protein binding, first pass metabolism

Answer 27

biological factors to consider for modified release dosage forms

Question 28

floating system (inherent low density --> lower than water, low density due to swelling, gas-generating and entrapment), mucoadhesive or bioadhesive systems, hydrodynamically balanced systems (HBS), raft-forming systems, superporous hydrogels (increase pores to float)

Answer 28

mechanisms to increase GI residence

Question 29

example: metformin ER tab, effervescent floating system, film coated tablet

Answer 29

gas-generating systems

Question 30

barrier formed by a this system example: cytotec (misoprostol) - prostaglandin to reduce the risk of NSAID induced gastric ulcers, bilayer floating technology

Answer 30

raft-forming system

Question 31

tablets swell to the point where it becomes too big to exit the stomach, take with plenty of water

Answer 31

superporous hydrogels

Question 32

unique gastroretentive formulation composed of pharmaceutical biodegradable polymeric films (clinical trial Carbidopa/Levodopa with this system) multilayer planar structure folded to an accordion shape into standard size regular capsule, keeps accordion in stomach for extended period of time

Answer 32

accordion pill

Question 33

invasiveness (bypassing natural defense systems), should be sterile and high quality

Answer 33

similarities between types of parenteral drug delivery

Question 34

sites of drug deposition, rate of absorption, applications/purpose

Answer 34

differences between types of parenteral drug delivery

Question 35

smaller gauge means what size diameter?

Answer 35

larger

Question 36

drug will be immediately diluted into blood, veins less sensitive than tissues for IM/SC injections

Answer 36

IV administration considered safe for irritant drugs like chemo

Question 37

bolus/push (small volume parenterals), continuous infusion/drip (dosing over extended period, large volume parenterals), intermittent infusion (multiple doses given over a short period repeatedly, Patient Controlled Analgesia/PCA)

Answer 37

IV drug administration

Question 38

1. solutions: aqueous, aqueous and cosolvents, surfactant based preparations (micellar solutions) 2. powder for infusion: reconstitute, Secretin which is a diagnostic agent to assess pancreatic function 3. O/W emulsions: have to be O/W because can't administer oily stuff this way because can cause pulmonary embolism/occlude capillaries, TPN, lipid emulsion, aprepitant, clevidipine 4. novel drug delivery systems: liposomes, nanoparticle suspensions

Answer 38

IV formulations

Question 39

- amino acids, dextrose, soybean oil, calcium chloride, magnesium sulfate, potassium chloride, sodium acetate, sodium glycerophosphate - stable intravenous fat emulsion has all 3 macronutrients in same mixture - formulation of dextrose and amino acids with separate lipid infusions an option too

Answer 39

TPN IV emulsion

Question 40

rapid onset of effect and 100% bioavailability (most efficient in life threatening situations), ability to rapidly titrate the dosage to achieve the desired clinical outcomes (can keep adding drug until get desired response), more precise control of drug levels, provide for controlled and constant plasma profiles and maximum volumes, suitable for patients with GI issues (bypass first pass metabolism)

Answer 40

advantages of IV medications

Question 41

18-25G 0.5-1.5" needle, 90 degree angle injection, Z track method of injection seals medication within target tissue

Answer 41

IM injection

Question 42

- select the site and needle size most appropriate for the patient to administer medication into muscle tissue, not blood vessels - generally not recommended during IM injection with low risk of adverse effects - may be indicated if medication has high risk of adverse effects - recommended against during vaccine injections because it increases pain with no benefit

Answer 42

aspiration

Question 43

- medical device designed to deliver IM or SubQ dose, patient self administration (safe and easy to use) - drug delivery/activation mode (spring type and position) - needle protection and needlestick prevention --> needle retraction or needle shroud to encase the needle - preactivation safety features - needle insertion - arming auto-injector --> manual or prearmed - dosing --> fixed dose, variable dose, multiple dose - type of device --> single-use, resusable

Answer 43

auto-injectors

Question 44

1. immediate release - aqueous and nonaqueous solutions - emulsions (both types), oily solutions, suspensions 2. sustained release (IM depot) - oil based solutions - suspensions for sustained release - in-situ depot forming systems - implants, microparticles

Answer 44

IM formulations

Question 45

23-13G 1/2 to 5/8 inch needle, 45-90 degree angle, do not aspirate

Answer 45

SubQ injection

Question 46

- hydration for a specific patient population - nauseated or vomiting, dysphagia, delirium, confusion

Answer 46

SubQ infusion - hypodermoclysis

Question 47

- usually smaller in volume than counterpart - insulin, glucagon, ozempic - abaloparatide (Tymlos) - anticoagulant (dalteparin/Fragmin, enoxaparin/Lovenox, fondaparinux/Arixtra) - antineoplastic agents (azacitidine/Vidaza, leuprolide/Eligard), methotrexate/Otrexup/Rasuvo) - Antihypertensive/loop diuretics (furosemide/Furoscix) - Opioid analgesic (buprenorphine, methylnaltrexone) - Antimigraine agent (sumatriptan/Imitrex) - antipsychotic (risperidone) - vaccines, others

Answer 47

SubQ products

Question 48

skin pricking or scratch test , TB vaccination that can't be administered IV

Answer 48

percutaneous administration

Question 49

involves injecting a substance into the dermis of the skin, diagnostic testing for allergies, penicillin, skin test for TB

Answer 49

intradermal administration

Question 50

- issues or mistakes in administration - irritations and extravasation - incompatibilities (IV admixtures) - infection during or at site of injection due to microbial contamination - safety issues concerning sterile products (need strict adherence to USP Chapter <797>) - speed shock/circulatory overload (sudden adverse reaction to IV medications) - anaphylaxis/allergic reactions - vascular access devices (VAD) and catheter complications

Answer 50

parenteral complications

Question 51

hand hygiene, protective wear like gloves, clean workspace, sterile supplies, vial preparation with alcohol swab, site preparation like skin disinfection, proper injection technique, post-injection care

Answer 51

preventing infection during injection

Question 52

inflammation of the veins

Answer 52

phlebitis

Question 53

inflammation of veins and formation of a clot

Answer 53

thrombophlebitis

Question 54

sterile and aseptic processing, pyrogen free within USP limits, free from particles/clarity because particles can occlude capillaries, stability, osmotic pressure (tonicity), pH, buffers, high quality excipients and packaging

Answer 54

features of parenterals

Question 55

sterilization of final product

Answer 55

terminal sterilization

Question 56

transfer final product after this, sterilize each individual component of the product

Answer 56

aseptic processing

Question 57

- steam (autoclaving, steam under pressure) - filtration (removal of microorganisms using 0.2-0.22 micron filters, aseptic processing only for solutions) - dry-heat (hot air ovens at 300-340 F for 1 - 2.5 hours, higher temperature less time, powders, petroleum products, sharp instruments) - gas (exposure to ethylene oxide gas which is a toxic gas that has to be removed before administration) - ionizing radiation (exposure to high energy ionizing radiation like gamma/X rays and electron beams, can sterilize rooms this way)

Answer 57

methods of sterilization

Question 58

1. membrane filtration (product is filtered with 0.45 micron filters, filter is transferred to growth media, high pressure but not too high as to not kill the microorganisms) 2. direct inoculation of the culture medium (method of choice for medical devices)

Answer 58

sterility testing

Question 59

soybean casein digest medium is used for _________, fluid thioglycollate medium is used primarily for ________, and alternative thioglycollate medium is used for __________

Answer 59

1. aerobes 2. anaerobes 3. viscous products

Question 60

fever inducing substances

Answer 60

pyrogens

Question 61

toxic substances secreted by certain living bacteria

Answer 61

exotoxin

Question 62

lipopolysaccharides (LPS) from bacterial cell wall, thermostable, water-soluble, unaffected by bactericides, non-volatile

Answer 62

endotoxins

Question 63

ultrafiltration, distillation, inactivation by extreme heat (180 C/356 F for 3 hours)

Answer 63

depyrogenation

Question 64

rabbit test, bacterial endotoxin test (LAL test) - gel clot (coagulation or gel) - turbidity (cloudiness) - chromogenic assay (color indicator)

Answer 64

pyrogen testing

Question 65

1. freedom from particulates - mechanical pulmonary artery obstruction (occlude small capillaries) - injection site reaction 2. stability - loss of activity - toxicity due to degradation of products 3. isotonicity - freezing point depression - sodium chloride equivalent

Answer 65

features of high quality products

Question 66

most reliable, repeatable, productive inspection method (ampules or glass containers) with the following advantages: 1. detectability of less than 5 micron sized holes 2. detectability of cracks 3. 100% non-destructive 4. no secondary contamination of the product 5. 100% inspection possible

Answer 66

high voltage leak detection (HVLD)

Question 67

1. active ingredient 2. water and sterile water injection, bacteriostatic water for injection 3. co-solvents like ethanol, PEG, PG, glycerin 4. surfactants and fixed oils like lecithin, polysorbate, peanut oil, sesame oil, soybean oil 5. antioxidants like ascorbic acid, sodium bisulfite, sodium metabisulfite 6. buffers like acetic acid, citric acid, corresponding salts 7. tonicity adjusting agents like NaCl, dextrose, glycerin, lactose, mannitol, sorbitol 8. Chelating agents like EDTA 9. Preservatives like benzyl alcohol, paraben, benzoic acid, benzalkonium chloride phenol, thimerosal

Answer 67

formulation/components of small volume parenterals

Question 68

clean area (air supply and airflow with HEPA filter that removes 99.97% of 0.3 micron or larger particles, laminar flow hood/cabinet), aseptic preparation, finishing and packaging, quality control (sterility testing, clarity, pyrogen testing)

Answer 68

production/compounding facilities have these things

Question 69

parenterals that are administered in less than 100 mL, aqueous and nonaqueous, may contain preservatives, buffers, solubilizers/cosolvents, antioxidants, ampules, vials, prefilled syringes

Answer 69

small volume parenterals

Question 70

parenterals that are aqueous only, no preservatives or antioxidants, used as a vehicle for delivery of drug/fluid replacement/delivery of nutrients (TPN), comes in glass bottle or plastic bag, dialysis fluids, irrigation solutions

Answer 70

large volume parenterals

Question 71

glass container for up to 100 mL, single dose, must break the top off to access the solution, no powders because can't add solvent and shake once the neck of this is broken, preservatives not recommended

Answer 71

ampules

Question 72

glass container with rubber membrane (septum), can be used more than once, often with dry powder for reconstitution (lyophilized)

Answer 72

vials

Question 73

administration of these is more convenient for healthcare professionals and end users, reduction of medication errors, better dose accuracy, commonly used for controlled drug substances, easy storage and disposal, dual chamber cartridges and syringes

Answer 73

prefilled syringes

Question 74

IV fluids containing electrolytes, isotonic, hypertonic, hypotonic, NS, D5W, LR, D5NS, D5LR, D10, 1/2NS

Answer 74

crystalloid solutions

Question 75

IV fluids containing large proteins and molecules that tend to stay within the vascular space, plasma protein fraction, salt-poor albumin, dextran

Answer 75

colloid solutions

Question 76

IV products for patients with EDEMA or CHF (promote diuresis by drawing fluid from the cells into the plasma (patient should be on diuretics), mannitol injection 10, 15, 20, 25% solutions, extravasation at greater concentrations), HYPONATREMIA (low sodium in the blood, excessive water intake, vomiting, excessive sweating, heart failure, losing blood because of injury, up to 3% NaCl peripheral, greater than that is central line only), METABOLIC ACIDOSIS (chronic kidney disease, diabetic ketoacidosis, sodium bicarbonate solutions), WATCH OUT for circulatory overload and patient response

Answer 76

hypertonic IV solutions

Question 77

IV products that provide free water or artificial hydration, 1/2NS, when the body has lost water only without losing any electrolytes, hyperosmolar diabetes, metabolic alkalosis, patients need to be monitored for hyponatremia/water intoxication

Answer 77

hypotonic IV solutions

Question 78

drugs that are not stable in solution form are prepared as dry sterile solids which are dissolved in water for injection just before administration, methods of preparation include lyophilization (freeze drying), sterile recrystallization, spray drying

Answer 78

sterile powder for solution

Question 79

sterile aqueous solution of drug is frozen, then subjected to high vacuum, water sublimes, only drug and other ingredients remain in a solid state, absence of water leads to better stability because no hydrolysis, water is added back when it is ready to be administered to patient (reconstitution)

Answer 79

lyophilization

Question 80

these products provide simple administration (easy to handle), increased patient safety through all in one concept, improved compatibility and stability, types (lyophilized/solvent drugs, liquid/liquid drugs, powder/liquid drugs)

Answer 80

dual chamber cartridges/syringes

Question 81

intracavernous injection for erectile dysfunction, lyophilized single dose dual chamber cartridges

Answer 81

Edex (alprostadil)

Question 82

dispersed, heterogeneous systems containing insoluble drug particles, for drugs that are unstable or insoluble, aqueous or vegetable oil vehicles

Answer 82

suspensions

Question 83

dry sterile solids that are suspended in the vehicle just before administration, should be easily resuspended, should be easily injectable (passed through 18-21G needle), methods of preparation include lyophilization (Abilify Maintena IM prefilled syringe, dual chamber system), spray drying

Answer 83

sterile powders for suspension

Question 84

albumin-bound IV suspension paclitaxel, nanoparticles too small to occlude capillaries so can be suspension for IV, chemotherapy, lyophilized powder for reconstitution with NS, free from cremophor EL which can be toxic, EPR effect (active and passive targeting)

Answer 84

Abraxane 100 mg

Question 85

enhanced permeability and retention, tumors have leaky blood vessels, ineffective lymphatic drainage, allow large nanoparticles, allows to selectively target tumors (passive targeting), active targeting involves protein bound tumor specific effects

Answer 85

EPR effect

Question 86

TPN, IV emulsion products (Cinvanti/Aponvie aprepitant for prevention of chemotherapy-induced nausea and vomiting)

Answer 86

IV emulsions

Question 87

spherical vessels made up of lipid bilayer, inside is aqueous/hydrophilic and middle layer is hydrophobic, outside is hydrophilic, improve solubility and compatibility (able to dissolve both lipophilic and hydrophilic drugs in one system), provide sustained release, improve efficacy and reduce toxicity, target the site of action, example is AmBisome (amphotericin B) which is an IV infusion, antifungal for cancer patients, decreases nephrotoxicity, another example is Doxil (doxorubicin) for IV piggyback only, chemotherapy, evade detection by immune system because of PEGylation, increase stability of liposomes, circulates in the body for a longer period and targets cancer cells (EPR effect)

Answer 87

liposomes

Question 88

controlled/sustained drug delivery for over a long time (months to years), reservoir or matrix systems, can be biodegradable (go away on their own) or non-biodegradable (need to have them removed), improve patient compliance but may require mini surgery, uneasy to simply discontinue, local reactions, example is Nexplanon (etonogestrel SC) which is a contraceptive that lasts up to 4 years, single rod, contains barium sulfate for ease of removal

Answer 88

implants

Question 89

examples of this include Scenesse (afamelanotide) and Supprelin LA (histrelin acetate)

Answer 89

subcutaneous implants

Question 90

polyanhydride wafers containing carmustine, FDA approved chemotherapy implant that delivers drug directly into surgical cavity created when brain tumor is resected

Answer 90

Gliadel wafer

Question 91

non-peristaltic programmable implantable pump (microcatheter in lower spine)

Answer 91

Prometra intrathecal drug delivery

Question 92

liquid preparation that upon injection will convert into a gel in body to form a depot (implant), easy to administer (syringeability), thermoplastic pastes, cross-linked polymer systems, polymer precipitation (organogels), thermally induced gelling systems, lipid nanodispersions

Answer 92

in situ gels

Question 93

a peripheral or coronary stent placed into narrowed, diseased peripheral or coronary arteries that slowly releases a drug to block cell proliferation, sirolimus-eluting stents (SES), paclitaxel-eluting stents (PES)

Answer 93

drug eluting stents

Question 94

eliminate fear of needles, elimination of needle stick injuries to healthcare workers, limitations include higher cost, higher incidence of irritation

Answer 94

needleless injector system