Common preservatives added to prevent microbial activity

Benzoic Acids Sorbic acid Butyl Parabens pH 5, because it's not ionized

pH at which preservatives lose their antimicrobial activity and why

Glycerin (3) and problem

triol that does not have the same depressant effects as ethanol mixes with propylene glycol, water, alcohol and PEG400 humectant and preservative problem: increased viscosity

Alcohol

solvent children under 6- 0.5% 6-12- 5% 12-adult- 10% diol miscible with water, alcohol, PEG 400

propylene glycol

Antioxidants (and 4 examples)

preservative ascorbic acid, sodium metabisulfate, alpha tocopheral, butylated hydroxytoluene

aspartame

sweetener do not use with patients who have phenylketonuria

sucrose

sweetener can cause GI upset to young and old patients (high osmotic load making a hyperosmotic solution)

vin marini

cocaine laced drug in the 1880-1906 time period caused the Pure Food and Drug act

diethylene glycol

causes kidney failure; was used as solvent for sulfanilamide. caused 1938 food, drug, cosmetic act

thalidomide

birth defects; caused Kefauver-Harris amendment requiring safety and efficacy testing as well as teratogenicity tests in pre-clin

investigational new drug application types (3)

commercial (most common) single investigator (for one physician at one study site- usually for dosing regimens of approved drug) Emergency/Compassionate- for incurable patients who don't meet requirements for ongoing treatment protocols

types of conventional solid dosage forms (4)

lozenge capsule tablet powders emulsion elixir suspension syrup solution

common liquid forms (5)

dentifrice

bulk powder, usually contains soap/detergent, anticariogenic agent (prevents cavities), and an abrasive

effervescent granules

contain sodium bicarbonate + citric acid or sodium biphosphate. releases CO2 and masks bitter medications

enteric coated tablets

pass through stomach to dissolve in GI (protects against stomach acid?)

1888- what was established?

national formulary

some advantages of powders/granules (solid) 4

easier to prepare big doses faster dissolution flexible for compounding solids solids are more stable not convenient to carry around not good for drugs that are inactivated in stomach not suitable for dispensing hygroscopic drugs hard to mask unpleasant taste bulk powders not good for administering low doses of potent drug accurate doses can be administered simply easy to transport in bulk more stable than liquid mass produced quickly release rate can be customized

disadvantages of powders/granules (5)

advantages of compressed tablets (5)

disadvantages of compressed tablets (4)

tablet coating hard to perfect compression can change physical properties, particle size, crystal form tablet disintegration can be a rate limiting step if drug dose is large, big tablet is hard to swallow

advantages of hard capsule (4)

disadvantages of hard capsules (5)

Better bioavailability than tablets Flexibility in formulation in comparison to tablets Bead type release products can be filled without problems associated with compression Ideal or clinical trials and widely used for preliminary drug trials Number of suppliers of shells is limited Filling equipment slower than tableting Generally more costly than tablets Not suitable for highly soluble salts rapid release causes gastric irritation Hard gelatin capsules (and tablets) can become lodged in the esophagus Liquid fill is metered resulting in higher degree of reproducibility Higher degree of homogeneity Rapid release of liquid may result in better bioavailability Hermetically sealed as part of the process Wide variety of sizes and shapes available Limited number of companies Expensive compared to tablets Shell and liquid products in greater contact than solid contact greater potential for interactions Drug might migrate into shell homogeneous ease of preparation can be sweetened/flavored dose is easily changed by adjusting volume easier to swallow KCl causes ulcerations in tablet form so need to use liquid can be used orally, parenterally, topicaly susceptible more to degradation so shorter shelf life some things taste/smell bad in solution bulk and fluidity (takes up lots of shelf space) need special storage (e.g. refrigerator) patient needs to be able to see susceptible more to microbes medical- drug efficacy and safety chemistry- manufacture ok? GMP? statistics- validate study design clin. pharm/biopharmaceutics- drug disposition, in vitro ADME tox/pharm- in vivo ADME, carcinogenicity, teratogenicity project management- interface between review staff and manufacturers new drugs, therapeutic devices, and cosmetics must be shown to be safe before marketing authorized factory inspections eliminate need to prove intent to defraud in misbranding added safe levels for unavoidable poisonous substnaces

advantages of soft capsules (5)

disadvantages of soft capsules (4)

advantages of liquids (7)

disadvantages of liquids (6)

parts of the FDA review team (6)

food drug and cosmetic act of 1938 (4)

type 1 NDA

not available in US

types 2 NDA

derivative of active approved moiety in US

type 3 NDA

new formulation

type 4 NDA

new combination with other approved drug

types 5 NDA

new manufacturer

advantages of liquids (7) Select the best answer homogeneous ease of preparation can be sweetened/flavored dose is easily changed by adjusting volume easier to swallow KCl causes ulcerations in tablet form so need to use liquid can be used orally, parenterally, topicaly accurate doses can be administered simply easy to transport in bulk more stable than liquid mass produced quickly release rate can be customized medical- drug efficacy and safety chemistry- manufacture ok? GMP? statistics- validate study design clin. pharm/biopharmaceutics- drug disposition, in vitro ADME tox/pharm- in vivo ADME, carcinogenicity, teratogenicity project management- interface between review staff and manufacturers not convenient to carry around not good for drugs that are inactivated in stomach not suitable for dispensing hygroscopic drugs hard to mask unpleasant taste bulk powders not good for administering low doses of potent drug

Question 3 No answer. The correct answer is highlighted. Multiple-choice advantages of soft capsules (5) Select the best answer Better bioavailability than tablets Flexibility in formulation in comparison to tablets Bead type release products can be filled without problems associated with compression Ideal or clinical trials and widely used for preliminary drug trials Liquid fill is metered resulting in higher degree of reproducibility Higher degree of homogeneity Rapid release of liquid may result in better bioavailability Hermetically sealed as part of the process Wide variety of sizes and shapes available medical- drug efficacy and safety chemistry- manufacture ok? GMP? statistics- validate study design clin. pharm/biopharmaceutics- drug disposition, in vitro ADME tox/pharm- in vivo ADME, carcinogenicity, teratogenicity project management- interface between review staff and manufacturers homogeneous ease of preparation can be sweetened/flavored dose is easily changed by adjusting volume easier to swallow KCl causes ulcerations in tablet form so need to use liquid can be used orally, parenterally, topicaly

Question 4 No answer. The correct answer is highlighted. Multiple-choice thalidomide Select the best answer accurate doses can be administered simply easy to transport in bulk more stable than liquid mass produced quickly release rate can be customized preservative ascorbic acid, sodium metabisulfate, alpha tocopheral, butylated hydroxytoluene easier to prepare big doses faster dissolution flexible for compounding solids solids are more stable

birth defects; caused Kefauver-Harris amendment requiring safety and efficacy testing as well as teratogenicity tests in pre-clin

Question 5 Incorrect. The correct answer is highlighted. Multiple-choice enteric coated tablets

Select the best answer diol causes kidney failure; was used as solvent for miscible with water, alcohol, PEG sulfanilamide. caused 1938 food, drug, cosmetic 400 act pass through stomach to dissolve in GI (protects against stomach acid?) emulsion elixir suspension syrup solution

Question 6 Incorrect. The correct answer is highlighted. Multiple-choice disadvantages of powders/granules (5) Select the best answer not convenient to carry around not good for drugs that are inactivated in stomach not suitable for dispensing hygroscopic drugs hard to mask unpleasant taste bulk powders not good for administering low doses of potent drug tablet coating hard to perfect compression can change physical properties, particle size, crystal form tablet disintegration can be a rate limiting step if drug dose is large, big tablet is hard to swallow triol that does not have the same depressant effects as ethanol mixes with propylene glycol, water, alcohol and PEG400 humectant and preservative problem: increased viscosity

commercial (most common) single investigator (for one physician at one study site- usually for dosing regimens of approved drug) Emergency/Compassionate- for incurable patients who don't meet requirements for ongoing treatment protocols Question 7 Incorrect. The correct answer is highlighted. Multiple-choice types 5 NDA Select the best answer

solvent children under 6- 0.5% derivative of active approved moiety in US 6-12- 5% 12-adult- 10% new manufacturer national formulary Question 8 No answer. The correct answer is highlighted.

Multiple-choice dentifrice Select the best answer solvent bulk powder, usually contains soap/detergent, anticariogenic children under 6- 0.5% agent (prevents cavities), and an abrasive 6-12- 5% 12-adult- 10% sweetener do not use with patients who have phenylketonuria Question 9 Incorrect. The correct answer is highlighted. Multiple-choice type 1 NDA Select the best answer new formulation new combination with other approved drug new manufacturer not available in US Question 10 Incorrect. The correct answer is highlighted. Multiple-choice types 2 NDA Select the best answer Benzoic Acids derivative of active approved moiety in US Sorbic acid Butyl Parabens new manufacturer diol miscible with water, alcohol, PEG 400 diol miscible with water, alcohol, PEG 400