Blueprint Diagnostic C/P Passage 1

Session 261

Today, we dive into the Blueprint diagnostic and go over Chem/Phys passage one! If you’re looking to review your FREE diagnostic, check out this episode!

We’re joined by Alex from Blueprint MCAT. If you would like to follow along on YouTube, go to premed.tv.

Listen to this podcast episode with the player above, or keep reading for the highlights and takeaway points.

[04:29] General MCAT Test-Taking Tips

One of the big things for the MCAT is recognizing they’re going to throw a bunch of words at you that you’ve never seen before or that seemed to be in areas you know nothing about.

'The MCAT is an exercise in using what you know to figure out what you don't.'Click To Tweet

You’re not expected to know anything about, in this passage, oral delivery systems. But you can use the content knowledge you will be expected to know to puzzle out the answers anyway.

[05:41] Passage 1 (Questions 1 – 5)

Paragraph 1

Oral drug delivery systems are limited by the short gastrointestinal transit time, leading to low bioavailability. Drug delivery systems able to retain the dosage form in the stomach are needed. Research into floating drug delivery systems (FDDS) may satisfy this need.

Notes:

You’re not expected to know anything about floating drugs when you walk into the MCAT. But you are expected to know about drug absorption in general and buoyancy.

[08:08] Paragraph 2

FDDS can be approached by either effervescent or non-effervescent techniques. Ideal effervescent techniques achieve floating duration times > 16 hours in the stomach. Effervescent FDDS incorporate gas-generating agents, which provide buoyancy. Newer research focuses on non-effervescent systems, where the swelling of polymers joined to the drug entraps air within the polymeric matrix, providing buoyancy to the dosage form.

Notes:

Now we know that the floating drug delivery systems have two subtypes. And so, we highlight effervescent and non-effervescent. You don’t have to highlight anything else. Anyway, if they bring this up, then we know where to find that.

[10:42] Paragraph 3

A study was performed on the antidiabetic sulfonylurea glipizide. The drug and one of three polymers were mixed in a mortar according to the ratios described in Table 1. A drop of water was added, and the mixture was kneaded until a homogenous paste was obtained. The mixture was then placed in an oven at 50°C for 30 min to remove water. The compound was then compressed into tablets which served as the basis for drug release and buoyancy measurements.

Table 1 The density of glipizide and the three polymers and the drug to polymer ratio in each trial

Notes:

This paragraph talks about researching the non-effervescent type. In the previous paragraph, we know that non-effervescent systems use polymers. And in this paragraph, we’re mixing the drug with a polymer.

Just highlight the “study was performed” and “the drug and one of three polymers were mixed.” The rest is specifics and you don’t have to memorize these kinds of data on the MCAT.

[14:22] Paragraph 4

To test in vitro drug release of solid dispersions, the tablets were placed into dissolution vessels containing 900 mL of 0.1 M HCl. Dissolution studies were carried out for one hour, with samples withdrawn at predetermined intervals. Drug concentrations were assayed using HPLC methods. The dissolution experiments were carried out in triplicate, and the results are shown in Figure 1. In vitro buoyancy was also tested. Tablets were placed in a vessel containing 500 mL of 0.1 M HCl. The time taken for the tablet to rise to the surface of the dissolution media (floating lag time) and total duration that the tablet remained on the surface (total floating time) were recorded.

Figure 1 Drug release as a function of time and pill composition

Notes:

We’re getting more methods here and they’re telling us what they did.

[17:14] Paragraph 5

The Ksp for glipizide-cyclodextrin in a chyme solution at 37ºC was determined to be 5.8 x 10-4. Increased solubility of drug dispersions may be achieved by wetting via hydrophilic polymers, or by polymer size reduction.

(Note: all pills for the above trials have the same volume.)

Notes:

KSP refers to the solubility constants for this particular drug-polymer combination. And this ties into equilibrium chemistry, which many people are studying for this test.

[19:11] Mindset Shift When Jumping to Questions

'Whenever you see anything on the MCAT that you don't remember completely, don't panic because it hasn't asked you a question on it yet.'Click To Tweet

Every question is pointing at a component of the passage, or it’s pointing at a component of your prior content knowledge, or it’s pointing at a mixture of both.

Your job as an MCAT test-taker is to identify and find that piece of information, either in the passage or in your brain. Apply it or mix them together and pick the answer.

[19:51] Question 1

Which of the following correctly lists the floating lag times for the three trials in increasing order? (note: assume that the mixing of the drug and polymer does not change the density of either component)

A.Trial 1 < Trial 2 < Trial 3

B.Trial 2 < Trial 1 < Trial 3

C.Trial 3 < Trial 2 < Trial 1

D.Trial 2 < Trial 3 < Trial 1

Thought Process:

They haven’t presented us with all of the researcher’s data. It says they measured floating lag time, but we don’t see that presented to us. And so, we must be able to figure it out another way.

The keyword right here in the question stem is floating lag time, and you need to know what this is. Look at that in the methods paragraph, where they tested the in vitro drug release of solid dispersions. Look at the definition of floating lag time given, which is the time taken for the tablet to rise to the surface of the dissolution media.

So we’re dropping this tablet into this container of liquid and then we’re measuring how long it takes for it to float back up to the top. And density is the primary determinant of how quickly something will float.

We’re looking for the pills with the greatest and the least density. And we’re looking for floating lag times in increasing order. If a pill rises the fastest, then will have the lowest density. So the first pill in this list should be the pill with the lowest density. And we get that information in Table 1.

There are three trials here, and we’re mixing in different ratios of polymers with this drug. And we get the density of the drug and the polymer. And it looks like all three trials have a different ratio of drug to the polymer. If you assume that the mixing of the drug than the polymer does change the density of either component, then we can no longer do the math to figure out what the average density of the pill is given its components.

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Looking at the densities of these pills, you could take a weighted average of this table. Now, figuring out that for all of the three trials is a lot of math that’s going to take a long time. So just try to figure out what’s first.

Poloxamer 188 is by far the least dense polymer and it makes up a much higher proportion of the pill in trial three than the other polymer is doing any of their trials. So whatever the case, trial three will be the first thing on this list. And that’s all you need to get to the correct answer.

Correct Answer: C

[34:38] Question 2

Tolazamide is an aromatic drug with a similar sulfonylurea structure to glipizide. Which of the following is most likely tolazamide?

Thought Process:

The most common aromatic ring that people are generally familiar with is benzene or phenol. In fact, the aromatic nature of the ring is one of the reasons phenol is so acidic.

Then look at the similar sulfonylurea structure to glipizide. The definition of a urea group is a carbonyl group with two organic amines branching off on either side. And both A and D have that.

From those two pieces of information alone, we can get to the right answer because we already eliminated D because it didn’t have an aromatic ring. So A must be the correct answer.

Correct Answer: A

[38:35] Question 3

A student preparing for the experiments inadvertently adds an additional 400 mL of the same acid solution to the dissolution vessel. What will be the new pOH of this solution?

A.1.0

B.6.0

C.11.0

D.13.0

Thought Process:

This is another example of how the MCAT can take concepts that are straightforward in our minds initially, and then wrap our brains around themselves.

pOH is pH’s less often used cousin. But they are inverse to each other. Something with a low pH, something that’s very acidic, will have a high pOH. And that’s because when we sum them together, they’ll always sum to 14. So if something has a pH of 1, it’ll have a pOH of 13. For chemistry reasons, the concentration of high H+ ions and OH- in solutions are linked to each other. If you increase one, you decrease the concentration of the other.

So here, you can calculate the pH. Hydrochloric acid HCl, our concentration here is 0.1 Molar. HCl is a strong acid. So this will just completely dissociate into our final H+ concentration, which will be about 0.1 molars. We will take the negative logarithm of this to get the pH. The logarithm of 10 to the negative one is just its exponent. And the negative of -1 is 1. That’s our pH. And the pOH is whatever you have to add to that to get 14. Hence, D is the right answer.

Correct Answer: D

[44:20] Question 4

The flow rate of stomach content emptying is 100 cm3/sec. Patients who undergo gastric bypass surgery will increase this rate to almost 1600 cm3/sec. Assuming the flow of stomach contents approximates Poiseuille’s Law, what change to their gastrointestinal connection would explain this, provided no other changes occur in the conditions of stomach content flow?

A.The new connection is 2 times longer.

B.The new connection is 4 times longer.

C.The new connection radius is 2 times larger.

D.The new connection radius is 4 times larger.

Thought Process:

There’s more stomach liquid going through per second. That’s not necessarily the same thing as the stomach liquid is moving faster in meters per second.

If you don’t remember what Poiseuille’s Law is, D seems to be the most reasonable choice here. Eliminate A and C, because they are two times longer. Think about the change involved. You go from 100 cubic centimeters per second to 1,600.

If we’re doing something to the radius of the connection, and increase it by four times, and it went up by 16 times, then we know that this relationship is a square relationship. Since 16 is the square of 4.

In physics, it’s very rare for equations on the MCAT, to have anything to the fourth power, and Poiseuille’s Law is one of them. Poiseuille’s Law says that flow is equal to the pressure differential across the pipe, multiplied by PI multiplied by the radius of the PI to the fourth power. It’s divided by eight multiplied by the length of the pipe, multiplied by the viscosity of the fluid.

The equation predicts more flow if we either increase the pressure difference across the pipe. Increasing the radius would have more effect on flow. Increasing the length of the pipe would decrease the flow, or increasing the viscosity of the fluid would decrease the flow rate. And this is because they’re both in the denominator. So with this in mind, the new connection radius is two times larger and C is the correct answer here.

Correct Answer: C

[51:32] Question 5

When in vivo studies were performed on the three drug-polymer combinations, it was found patients in the poloxamer-188 group experienced the most stomach pains after administration. Given the results of the study, this is most likely due to:

A.elevated drug concentration causing inflammation of the gastric mucosa.

B.tablet fragments causing inflammation of the gastric mucosa.

C.glipizide/poloxamer-188 matrices being the smallest of the 3 tested.

D.increased pH of the stomach contents.

Thought Process:

This is a prime question you can solve with elimination because the correct answer will probably not be directly supported. But hypothetically, if it were true, could lead to the situation that was given in the stem.

A – Could an elevator drug concentration cause inflammation? Maybe, but that doesn’t explain why it happened in that in that poloxamer group, as opposed to the other ones. So we throw this out.

B – If for some reason this mixture was fragile and would break, then that would cause some inflammation. And so, this is the correct answer. It’s consistent with the observation that it dissolves the slowest.

C – This implies that reducing polymer size would increase your solubility. But we already know from the passage that this poloxamer trial dissolved the slowest. So if this were the case, that would imply that its matrix was larger than the others, not the smallest.

Correct Answer: B