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PHRM 828 > Exam 4 - Byrn > Flashcards

Exam 4 - Byrn Flashcards

1
Q

What is important to know about hydrolysis?

A

It is a major reaction that involves water attacking the molecule.

Molecule will cleave and break into two fragments.

Water often reacts and degrades a drug which is why it is important to not store medicines in a humid environment. EX: aspirin will start to smell like vinegar

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2
Q

What is the relationship between concentration and time (in hrs)

A

There is an accelerated breakdown of a drug in aqueous solution at elevated temperatures.

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3
Q

When is a solution stable?

A

At a certain concentration, for a certain time, at a certain temperature, at a certain degree of light exposure.

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4
Q

When is a solid drug stable?

A

For a certain time, at a certain temperature, at a certain degree of light exposure

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5
Q

When is compactability a problem?

A

It is a problem for longer infusion times with piperacillin, tazobactam, azithromycin, ciprofloxacin, tobramycin, vancomycin, insulin and some vasopressors.

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6
Q

What are common problems with drugs due to temperature?

A

High temps speed up chemical reactions and break down drugs and proteins.

Majority of IV drugs are refrigerated for longer stability except furosemide and phenytoin.

There is a handful of IV drugs that can be kept at room temperature such as metronidazole, moxifloxacin acetaminophen, acyclovir, pentamidine and valproate.

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7
Q

What is important to know about light exposure?

A

Light exposure can cause photodegradation and in some cases, increase formulation toxicity.

Amber vials protect from light.

Vitamin K, nitroprusside, doxycycline must be protected throughout administration.

Important to check drugs for color changes or change in appearance.

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8
Q

What is the definition of stability?

A

(Shelf life) stability is the extent to which a product retains the same properties and characteristics throughout its period of storage and use.

Certain functional groups are more susceptible to degradation.

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9
Q

What are 3 chemical reactions that cause drug degradation?

A

Oxidation-reduction
Hydrolysis
Photolysis

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10
Q

How can you prevent oxidation?

A

Protection from changes in temp.
Control pH with buffers.
Amber bottles to protect from light.
Store in colder temperatures to slow reaction.
Chelating agents (EX: EDTA) remove metal ions that can cause oxidation.
Antioxidants can remove free radicals produced by oxidation

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11
Q

What compounds are likely to be hydrolyzed?

A

Carbonyl, amide and cyclic groups

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12
Q

Is there a way to prevent hydrolysis?

A

Remove moisture (no water, hydrolysis can’t take place).
Freeze dry to remove water (lyophilization).
Avoid solids that absorb water (non-hygroscopic compounds).
Control the temperature.
Control the pH.

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13
Q

What are some of the functions of dosage forms?

A

Provide and accurate dose.
Promote drug dissolution.
Promote delivery to the site of action.
Ensure drug stability.
Control drug delivery in the body.
Determine dosage interval.

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14
Q

What is important to know about ester hydrolysis under basic conditions?

A

The reaction starts with a nucleophilic attack by the hydroxide anion on the ester carbonyl group.

Resulting in carboxylic acid and alcohol as the products.

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15
Q

What will help prevent the hydrolysis of esters and lactones?

A

Protection from moisture.
Protection from heat.
Controlling the pH in solution formulations.

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16
Q

What is important to know about the amide hydrolysis under basic conditions?

A

The reaction starts with a nucleophilic attack by the hydroxide anion on the amide carbonyl group.

Resulting in carboxylic acid and amine as the products.

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17
Q

What will help prevent the hydrolysis of amides and lactams?

A

Protection from moisture.
Protection from heat.
Controlling the pH in solution formulations.

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18
Q

What is important to know about he auto-oxidation of captopril?

A

Captopril is an angiotensin converting enzyme (ACE) inhibitor used to treat hypertension and congestive heart failure.

First one created.
Oxidation is caused by metal ions.

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19
Q

What are the most important things to know about oxidation and photolysis?

A

Oxidation is common, it is complicated route of degradation. May functional groups are subject to oxidation.

Oxidation can be minimized through protection of light, air, metals and addition of excipients.

Photolysis is drug degradation due to light exposure.

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20
Q

What are zero-order kinetics?

A

The rate order is constant.

Drug degradation is constant, independent of the concentration.

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21
Q

What are the stability issues for biologics?

A

Biologics are more fragile than small molecules since they are larger and more bonds can break.
Biologics can lose activity if they unfold.
Biologics can aggregate resulting in increased/decreased potency and adversue immune responses.

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22
Q

What’s the summary of biologics?

A

One of the fastest growing drug classes.
It includes, recombinant vaccines, vaccines, stem cells and gene therapy.
Protein drugs are more fragile, they are made of amino acids and fold a specific way.

23
Q

How do drug proteins degrade?

A

Through chemical and physical degradation.

Chemical: breaks or forms incorrect bonds, hydrolytic and oxidation reactions.

Physical: changes in protein structure without breaking covalent bonds, unfolding, and aggregation.

24
Q

What are common routes of protein degradation?

A

Hydrolytic (chemical): Asparagine (ASN) deamination and peptide bond clipping (hydrolysis).

Oxidation (chemical): Methionine (MET) oxidation and disulfide bond scrambling.

Aggregation (physical)

25
Q

What are the 5 main methods for ensuring quality of tablets and capsules?

A

Dissolution, assay, impurities, content uniformity, water.

Dissolution is the only one that can be linked to blood levels and bioavailability.

26
Q

What is the dissolution process?

A

The tablet must disintegrate before it is dissolve before it can be absorbed.

Drugs with high water solubility normally exhibit few formulation problems.

If drug has low water solubility, absorption rate can be governed by the dissolution rate.

27
Q

Which of the following isn’t true about the dissolution profile of methylphenidate and metadate CD?

The blue drug methylphenidate has a fast early dissolution rate.

Methylphenidate shows a higher total release.

Both are true.

A

Methylphenidate shows a higher total release.

Based off the graph that’s not true. Metadate CD does

28
Q

What should you know about solubility?

A

Solubility should be considered together with its dose.

Even poorly soluble drugs can completely dissolve under physiological conditions if the dose is small enough.

29
Q

When is a drug considered to have “high solubility” or “low solubility” ?

A

High solubility: when the largest human dose is soluble in 250 ml (or less) of water throughout the physiological pH of 1-8 at 37 degrees celsius.

Low solubility: when more than 250 ml is required to dissolve the largest dose at any pH at 37 degrees celsius.

30
Q

What is important to know about solubility and bioavailability together?

A

Bioavailability depends on having the drug in solution and drug permeability.

Jejunal permeability of at least 2-4 *10-4 cm/s is considered high.

The corresponds to the fraction absorbed of 90% or better.

31
Q

What is important to know about enteric polymers?

A

Allow the drug to be released in the intestine.

The omeprazole story.

Acrylate polymers
-Eudragit L and Eudragit S

CAP
HPMCP
PVAP

32
Q

What are matrix tablets and how do they work?

A

They are tablets where the drug is embedded in polymer matrix.

Erosion: drug is embedded in the matrix and tablet begins to erode as water enters.

Diffusion: drug is embedded in the matrix and outer layer has polymers that swell when they encounter water. The soft outer layer becomes a gel allowing for molecules to diffuse.

33
Q

How does the elementary osmotic pump in concerta work?

A

The membrane is semipermeable allowing for water to enter. Water will push the drug ingredient out of a laser drilled hole.

Single chamber: as water enters through the semipermeable membrane, drug ingredients are pushed out.

Double chamber: a rate controlling membrane allows water in at a certain rate, drug solution forms, push compartment hydrates expanding to push the drug out the hole.

34
Q

Which is not true?

A) Matrix tablets can show controlled release?
B) Coated tablets can show sustained release?
C) Oros tablets do not show controlled release?

A

C) Oros tablets do not show controlled release?

35
Q

What the difference in the dissolution graph between three 20 mg methylphenidate tablets and one 54 mg concerta?

A

The concerta (oros) tablet has a more gradual increase to 100% released and then plateaus off.

The methylphenidate has 3 distinct plateaus and levels off above 120% released.

36
Q

What was the advertising for concerta vs metadate CD?

A

“Metadate CD delivers peak exposure during critical learning hours”

The ad also claims that it achieves peak plasma levels 1.5 and 4.5 hours after taking the dose which is important for academic learning hours for kids to take once a day in the morning.

Additionally the metadata would have lower blood plasma levels around dinner and bedtime compared to concerta.

37
Q

Why is extended release important for an antiepileptic drug?

A

Serum drug concentration levels will remain more with in the therapeutic window.

Compared to immediate and delayed release which will peak quicker, last shorter and can cause toxic concentrations.

38
Q

What is the issue with generic concerta?

A

It doesn’t work the same as the name brand.

39
Q

What are a couple differences between IR and OROS?

A

Plasma concentration levels remain more consistent with OROS over hours compared to IR.

Dry mouth severity can increase in IR compared to extended release formulations.

40
Q

What are the 3 types of innovations?

A

Group A types: incremental tweaking of existing products. (Change tablet shape)

Group B types: based on analogy

Group C types: wild ideas

41
Q

What are the key points in a model for inventive ideation?

A

The problem will be in the center and surround it will be change, copy, combination, separate and convert.

Ritalin example:

Change: formulation
Copy: use oros as release
Combination: beads of different release profiles
Separate: use beads with different release

42
Q

What is the flow of the innovation pipeline?

A

Idea-concept-experiment-pilot-launch.

There gates throughout the innovation funnel that if they aren’t met, the idea won’t proceed.

43
Q

What’s important to know about the blue ocean strategy?

A

It is used to find and meet unmet needs of customers.

Create a map comparing which needs you meet and which needs you differentiate between offerings level and various criteria.

44
Q

What’s important to know about the lean startup?

A

It takes japanese lean manufacturing principles and applies them to product development.

Try, test, fail quickly, adapt/recycle.
Quick, dirty prototype testing
Get the minimum viable product
Leverage customer feedback during product development (do not waste time designing features customers do not want)

45
Q

What should you know about disruptive innovation?

A

The book we talked about was called the innovator’s dilemma.
-originated in Harvard 1995 based on a study of radical changes in technology

Typical a niche product at first, once the disadvantages are ironed out and accepted by the mainstream, then the current technology becomes obsolete.

Ex: fitbit, J&J spinning off new smaller companies

46
Q

What’s important to know about the US life expectancy?

A

It has risen since 1950 but decreased 1-2 years during COVID in 2020.

47
Q

What has been the innovation in HIV?

A

1981 AIDS first reported.
1987 First treatment (AZT) introduced.
- label expanded in 1991
1995 First protease inhibitors approved.
2001 First nucleotide analog approved.
2006 Mother to infant rate dropped to 2% US and first one a day pill approved.
2007 First C-C chemokine receptor type 5 antagonist approved
2012 Approval of first medicine for preexposure prophylaxis
2016 US death rate dropped 88% since 1996

48
Q

What should you know about the antiviral drugs solubility and bioavailability?

A

Antiviral drugs are typical very insoluble and have poor bioavailability.

2 solutions include prodrugs and formulation changes such as melt extrusion and spray drying.

49
Q

What is melt extrusion?

A

The API and matrix polymer are funneled into a long cylindrical grinder that first melts everything, then mixes it and homogenous the mixture before cooling and pushing out pellets.

50
Q

What is spray drying?

A

API and excipients are feed in through the top of a large drying chamber. The API and excipients are sprayed down and funneled into other tubes and funnels continuously decreasing the powder fraction.

51
Q

What are some pharmaceutical strategies for abuse-deterrent technologies?

A

Abuse-deterrent technologies make product manipulation more difficult to abuse and make it less attractive or rewarding.

Improved physical tamper resistance: OxyContin and Exalgo.

Incorporated deterrent: Suboxone and Embeda.

52
Q

What was special about the OxyContin formulation?

A

It has a PEO polymer mixture that become a gel when mixed with water so abuser wouldn’t be able to inject.

53
Q

Which is true about PEO
A)PEO does not form gels
B)PEO is not a critical component of many abuse
deterrent formulations
C)PEO forms a net structure with water to
produce a gel
D)None of these statements are true

A

C)PEO forms a net structure with water to
produce a gel

54
Q

Was reformulation of oxycodone sucessful?

A

Yes, there was a decrease in street sales and decrease in abuse by non-oral routes after the reformulation.

PHRM 828 (7 decks)

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