1
Q
- physiochemical properties of the drug and drug delivery system (drug release pattern - immediate/modified release, solubility, dissolution rate, permeability)
- biological factors (physiological fluctuations along the GIT like pH/secretions/motility/emptying rate/residence time, biochemical variance, anatomical differences like surface area/thickness/blood supply), effects of food and other drugs
A
factors influencing oral bioavailability
2
Q
ratio of the concentrations of a drug in a mixture of two immiscible liquids at equilibrium (octanol/water), measure of lipophilicity, logD
A
distribution coefficient
3
Q
Biopharmaceutics Classifications of Drugs class with high solubility and high permeability
A
Class I
4
Q
Biopharmaceutics Classifications of Drugs class with low solubility and high permeability
A
Class II
5
Q
Biopharmaceutics Classifications of Drugs class with high solubility and low permeability
A
Class III
6
Q
Biopharmaceutics Classifications of Drugs class with low solubility and low permeability
A
Class IV
7
Q
for oral drug delivery according to USP a drug substance is classified as highly ________ if the highest single therapeutic dose is completely _______ in 250mL or less (8 oz or less), should be studied over the pH range of 1.2 to 6.8 at 37 degrees C for stomach and small intestine
A
soluble
8
Q
high _______ can be concluded when the absolute bioavailability is greater than or equal to 85%, considering the drug is chemically stable in the GIT
A
permeability
9
Q
- reducing particle size, do this to increase the surface area, enhance solubility, and improve bioavailability for Class II or IV drugs
- example: Yonsa (abiraterone acetate), antiandrogen used for treatment of prostate cancer
- example: Griseofulvin
- example: Glyburide oral tablets, sulfonylurea, antidiabetic agent, administer with meals at same time each day, reduce hypoglycemia risk, absorption not affected by food
A
micronized formulations
10
Q
______ absorption is often irregular and unpredictable due to poor solubility and permeability, degradation by acid and enzymes, presystemic metabolism, variability in GI motility, effects of food
A
oral
11
Q
medications that irritate the ___________ mucosa: antibiotics (doxycycline), NSAIDs, bisphosphonates, chemotherapeutic agents, KCl tablets, etc., pill size and texture (large pills, poorly formulated products)
A
esophageal
12
Q
take medications with full glass of water, remain upright for 30 minutes after taking, avoid laying down immediately after taking pills, make sure to swallow pills correctly without crushing or chewing them, for patients with difficulty swallowing pills discuss alternatives like liquid formulations or smaller pills
A
patient counseling on preventing pill-induced esophagitis
13
Q
cephalic phase (20% of total acid secretion), gastric phase (pylorus only allows passage of liquid and small particles less than 2mm)
A
digestive (fed) phase of gastric emptying
14
Q
not eating phase, migrating motor complex
A
interdigestive (fasted) phase
15
Q
- phase I: 45-60 mins, no activity, rare contractions
- phase II: about 30 mins, intermittent contraction, increasing intensity
- phase III: 5-15 mins, intense and regular contractions, pylorus remains open, housekeeper waves
- phase IV: short period of transition to phase I
- all can transition to fed state with presence of food
A
migrating motor complex (MMC)
16
Q
________ release should not be taken before meals
A
delayed
17
Q
large surface area, mucosal folds, villi, microvilli, high blood flow which improves drug dissolution and absorption
A
small intestine
18
Q
varies with health, age, diet, concurrent drugs, fast transit means lower absorption, drugs that decrease GI motility may increase drug absorption
A
GI transit time
19
Q
much lower surface area compared to counterpart, not a major site of drug absorption, highly efficient reabsorption of water, rich in bacteria and bacterial enzymes (used for colon targeting)
A
large intestine
20
Q
absorption pathway, pores, solvent shift (moving fluids between cells)
A
convective transport
21
Q
absorption pathway, carrier-mediated, needs energy, iron supplements, levothyroxine tablets, methotrexate
A
active transport
22
Q
absorption pathway, diffusion supported by carriers, LATs, OCTs, OATs, PEPT1), carriers get saturated or inhibited, some vitamins, levodopa, metformin, trimethoprim, morphine, cimetidine, ranitidine, valacyclovir, fexofenadine, statins, beta-lactams, ACE inhibitors
A
facilitated transport
23
Q
absorption pathway, vesicles, vesicular transport
A
transcytosis
24
Q
absorption pathway, between cells, limited by tight junctions
A
paracellular permeation
25
absorption pathway, actively transported out of cells through P-glycoproteins
efflux transport
26
absorption pathway, absorption of drugs along with fats, highly lipophilic drugs absorbed this way
transcellular diffusion and incorporation into lipid particles
27
aqueous boundary layer (solubility and diffusion), epithelium (mucin, lipid bilayer), efflux transporters, chemical degradation, presystemic and first pass metabolism
barriers in GI
28
drug metabolism by GIT and hepatic enzymes, decreased bioavailability
presystemic metabolism
29
recirculation of drug, some drugs undergo this, biliary excretion of the drug and intestinal reabsorption, hepatic conjugation and intestinal deconjugation, rifampin is an example of a drug that does this
enterohepatic circulation (EHC)
30
alter gastric emptying time, alter pH, formation of drug-food components complex, increase viscosity of GI content, stimulate GI secretions, competes for specialized absorption mechanism, food-induced changes in pre-systemic metabolism and blood flow, food as a dissolution medium and absorption promoter
effects of food on oral drug delivery systems
31
delay the onset of therapeutic activity, avoid or reduce acute toxicity by keeping Cmax lower (tamsulosin, if taken with food can decrease adverse effects, safer)
delayed or slower absorption rate because of food
32
instability of drug in gastric fluid, chelation (complex interaction) with ions in the food, adsorption of the drug to food components, increased first-pass metabolism, leads to less drug available to have clinical effect
decreased absorption because of food
33
longer time for dissolution in the stomach, increased solubilization of the drug (pH effect), absorption with fats, reduced first pass metabolism
increased absorption because of food
34
viscous material empties at a slower rate in comparison to less viscous for increased gastric emptying time, delayed onset, decreased rate, prolong contact/stay in the gastric environment may affect drug stability, may improve bioavailability for drugs that dissolve slowly in the stomach at lower pH
food increases the viscosity of GI content
35
drug food interactions forming an insoluble complex, drug chelation, prevents drug absorption, dietary supplements
complexation
36
surface property, not chemical interaction, macromolecule complex (poor or no absorption), dietary fiber (cellulose, chitosan, pectin, xanthan gum, sodium alginate)
adsorption
37
food containing lipids stimulates secretion of bile, bile emulsifies and solubilizes lipids, influence drug absorption of lipophilic drugs
stimulation of GI secretions
38
improved absorption of lipophilic drugs (may be absorbed from small intestines along with digested fats), reduced first pass metabolism (if through lymphatic route - the lymphatic system does not connect to the portal circulation)
competition between food components and drugs for specialized absorption mechanisms
39
food components may inhibit CYP3A4 in intestinal cells leading to increased bioavailability of CYP3A4 substrates (stains, benzodiazepines, immunosuppressants), grapefruit inhibits drug metabolism by interfering with hepatic and intestinal CYP450 (atorvastatin and grapefruit leads to higher plasma concentration of atorvastatin)
food-induced changes in pre-systemic metabolism
40
monoamine oxidase metabolizes tyramine, if tyramine consumed while taking MAO inhibitor the tyramine levels will increase (phenelzine, selegiline), tyramine increases NE levels leading to hypertensive crisis, food high in tyramine (aged cheeses, cured meats, fermented foods, certain types of fermented/pickled foods, beans, alcoholic beverages)
tyramine-containing foods/beverages
41
food _________(increases/decreases) blood flow rate and increases bioavailability of compounds, hepatic blood flow, oral bioavailability
increases
42
increased solubilization of drug in food components, fatty food improves the dissolution of lipophilic drugs, use lipid based drug delivery systems (add a lipid as an excipient), food slows gastric emptying rate and that may improve dissolution rate
food promotes dissolution and absorption
43
dorsal tongue, gingiva, hard palate are keratinized (strong and hard) or nonkeratinized?
keratinized
44
cheeks, inner lips, ventral tongue, floor of mouth, soft palate are keratinized or nonkeratinized?
nonkeratinized
45
where is drug absorption faster (keratinized or non)?
nonkeratinized
46
- complex mixture of secretions from salivary glands, oral, pharyngeal, nasal mucosa, mostly water but also has electrolytes, buffers, mucins, digestive enzymes, statherins (remineralization), histatins (antimicrobial/antifungal)
- helps with transmucosal drug release (water-rich fluid), dilution and buffering, mucoadhesive dosage forms, excessive saliva flow (salivary washout of dosage form), digestive enzymes (stability of some drugs may be affected)
saliva
47
applied to oral mucosa (mucus membrane), rapid absorption, fast onset of action (highly vascular mucosal lining, suitable for emergency like nitroglycerin), no need for water, bioadhesive/mucoadhesive (buccal forms can provide ER), avoid the first pass metabolism (increase bioavailability and reduce adverse effects, reach required concentration with lower dose which decreases adverse effects), suitable for patients with dysphagia, unconscious or incapacitated, nauseated, patients on reduced liquid intake
oral transmucosal drug delivery
48
high doses cannot be administered because small surface area of absorption and limited residence time (unless bioadhesive), not suitable for bitter or irritating drugs or excipients that stimulate saliva production and promote swallowing, not suitable for uncooperative patients, patients may be restricted from eating, drinking, smoking, some dosage forms may affect oral hygiene, dentures, braces, damaged mucosa, precautions with products containing aspartame in patients with PKU
disadvantages of oral transmucosal drug delivery
49
administered under the tongue (small and flat tablet, compressed lightly), thin mucosa and highly vascular (fast absorption and increased AUC because avoids first pass metabolism), suitable for angina (nitroglycerin), pain (sufentanil, buprenorphine), migraine (ergotamine), schizophrenia (asenapine)
sublingual tablets
50
small flat tablet or film intended for oral transmucosal drug delivery, administered in the cheek or applied to upper gum, absorption is slower compared to sublingual (thicker mucosa and less permeable), Belbuca (buprenorphine), Sitavig (acyclovir), Oravig (miconazole)
buccal tablet/film
51
maximize the contact of the patch/tablets with oral mucosa to improve absorption, retain the dosage form in the oral cavity (patient can talk, drink, eat), bioadhesive polymers or buccal patch bind to gingival mucosa
mucoadhesive/bioadhesive
52
held in the mouth and allowed to dissolve slowly, local effect on the mouth and throat (clotrimazole) or systemic effect (fentanyl), tell patients how to take medication/storage and disposal/how to keep away from young children
lozenge/troche
53
creates a mist of liquid particles, metered valve releases contents in a controlled and uniform dose, Nitrolingual (nitroglycerin) translingual solution, can have local effects for cosmetics or dry mouth
aerosol solution/spray
54
nicotine (smoking cessation aid, OTC, bound to an ion exchange resin), chewing releases drug (chew slowly and stop chewing occasionally, most of the drug released from the gum is absorbed by oral cavity, fast onset of action and avoids first pass metabolism
medicated chewing gum
55
unique dosage form for persistent hemorrhoids, designed to get drug to site of action, hold drug at site of action for extended period (slit for flatulence), available only as compounded product, does not get lost in rectum but remains at point of application/insertion, treats internal and external hemorrhoids at same time
rectal rockets
56
highly vascular, superior rectal vein is portal (first pass metabolism), middle and inferior rectal veins drain into the inferior vena cava (avoid first pass metabolism), may result in erratic drug absorption (variable)
rectal vasculature
57
minimize the effect of first pass metabolism, avoid problems of oral drug administration like GI irritation, inactivation of drug, effect of food, suitable for patients unable to swallow (dysphagia, nausea vomiting, unconscious, infants/young children), provide local action (IBD, hemorrhoids, constipation)
advantages of rectal drug delivery
58
poor patient acceptance, erratic drug absorption from rectal route due to poor technique of insertion or disease conditions like diarrhea, not suitable for large volumes or drugs that irritate the rectum (unless laxative because large volume or irritation induce bowel movement)
disadvantages of rectal drug delivery
59
what type of suppository base melts at body temperature to release the drug (fatty or water soluble)?
fatty
60
what type of suppository base dissolves to release the drug (fatty or water soluble)?
water soluble
61
either melts or dissolves in rectal fluid, should be solid at room temperature for ease of insertion, non-irritating to rectal mucosa (water soluble bases are hygroscopic and irritant), should provide suitable drug release profile
desirable properties of suppository bases
62
solution or suspension, administered/injected into the rectum for cleansing/evacuating/local drug effect, Rowasa (mesalamine)
rectal enema
63
Cortifoam (hydrocortisone) and Uceris (budesonide) are examples of this, spreads well into the rectum, provides uniform coverage, retains in the rectum better, used for treatment of ulcerative colitis of the rectum (ulcerative proctitis)
rectal foam
64
diazepam comes in this form, for status epilepticus and breakthrough seizures, easy to administer in emergency, rapid onset of action
rectal gel
65
Rectiv (nitroglycerin) is an example of this
rectal ointment
66
hydrocortisone comes in this form, reduces inflammation, treats itching or swelling caused by hemorrhoids or idiopathic external anal pruritis, may require applicator or syringe
rectal cream
67
protective mucus, complex mixture of proteins and polysaccharides, suitable for transmucosal drug delivery, pH of this varies by age (lower at reproductive age)
vaginal fluid
68
good surface area and rich blood supply (avoids first pass metabolism and problems related to GIT), permeable to a wide range of compounds (peptides, proteins, steroids), provides targeted drug delivery to the uterus and surrounding tissues, poor patient compliance (difficult to use, poor patient acceptance, interfere with sexual activity, lack of retention), variability in drug absorption due to age, menstrual cycle, menopause, pregnancy
vaginal drug delivery
69
Cleocin (clindamycin) ovules, miconazole suppositories, terconazole suppositories all examples of this, oleaginous base
vaginal suppositories (ovules)
70
ointment, cream, gel, foam, uniform coverage and ease of spreading, easy to adjust dose, suitable for individualized medicine
vaginal semisolid dosage forms
71
1 day treatment, administer one applicatorful intravaginally at bedtime
Monistat vaginal ointment
72
medications to treat vulvovaginal candidiasis, bacterial vaginosis, and vulvar and vaginal atrophy associated with menopause come in this form
vaginal cream
73
medications to treat bacterial vaginosis, secondary amenorrhea, spermicide contraceptive, cervical ripening come in this form
vaginal gel
74
requires an applicator, provides uniform distribution over a large surface area, VCF (insert one applicatorful no more than one hour prior to intercourse - effective for up to one hour)
vaginal foam
75
NPO, elegant, no leak out, disintegrate or dissolve in vaginal fluid, could be bioadhesive, ease of application using an applicator, Vagifem/Yuvafem (estradiol)
vaginal tablets
76
softgel capsule (Imvexxy), suppository (Intrarosa), oblong shaped tablet (Endometrin), extended release device (Cervidil)
vaginal insert
77
solid dosage forms that dissolve when in contact with vaginal fluids, ease of application and longer retention time, more acceptable as compared with vaginal cream or gel, VCF
vaginal film
78
circular drug delivery system, made of flexible and non-irritating polymers, provides controlled/sustained drug release, Estring, Femring, Annovera, NuvaRing, EluRyng, EnilloRing, Haloette
vaginal ring
79
kills sperm cells, blocks cervix opening, absorbs and traps the sperm, Today (nonoxynol-9)
vaginal sponge
80
administer medications directly into urethra, localized treatment of conditions affecting the urinary tract (antibacterial, erectile dysfunction, urinary incontinence, urinary infections, cancer)
urethral drug delivery
Pharmaceutics II
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