[sharontee]

Hello all, I am trying to do a past paper question for the Hong Kong Pharmacy Registration Exam.
It is a pharmacy practise paper, but the question looks more chemistry. I am totally stumped, any help or pointers will be appreciated. Please let me know if should move this question to a different section.

Question:
5: A pharmaceutical free base has very poor solubility and oral bioavailability.You want to prepare pharmaceutical salts to overcome this
5a) Compared with a nitrate salt, the chloride salt fails to increase the oral bioavailability of this drug. Why would that be? Assume it is chemically stable and not extensively metabolized.(3 marks)

>>>> The only answer I could find is nitrate salts are all soluble, and all chloride salts are soluble apart from silver and mercury chloride?? Seems a really obscure answer?

5b) The intrinsic solubility of this drug is 1mcg/ml and the pKa is 2. Please estimate the solubility of the nitrate salt at the pH of the intestines (pH=6. by using mathematical or other approaches (4 marks)

>>>> Seems to be a mathematical problem, but doesn't provide enough info to do calculations?? I have got as far as the Henderson Hasselbach equation:

pH=pKa+log[A-]/[HA]
I know that the base has an intrinsic solubility of 1mcg/ml, and I assume I use this info to calculate at what pH this occurs, but how do I plug this value into the equation without any info on its molecular structure? And then how do I progress from there to the solubility of the nitrate salt??

Please help, thanks in advance

[Arkcon]

Hello all, I am trying to do a past paper question for the Hong Kong Pharmacy Registration Exam.
It is a pharmacy practise paper, but the question looks more chemistry. I am totally stumped, any help or pointers will be appreciated. Please let me know if should move this question to a different section.

Hi there.  We're glad to help, but I feel I have to remind you that our  forum Rules{click} specify that we only give hints.  I'm reminding you because your questions are very specific, so my general help may not solve your problems completely.

Question:
5: A pharmaceutical free base has very poor solubility and oral bioavailability.You want to prepare pharmaceutical salts to overcome this
5a) Compared with a nitrate salt, the chloride salt fails to increase the oral bioavailability of this drug. Why would that be? Assume it is chemically stable and not extensively metabolized.(3 marks)

This is a tough problem.  I'm not well versed in pharmacology, but this isn't a result I was expecting.  I can't solve this one.  However ...

>>>> The only answer I could find is nitrate salts are all soluble, and all chloride salts are soluble apart from silver and mercury chloride?? Seems a really obscure answer?

This answer of yours, isn't really an answer.  Its a high school level fact, that is correct, but it has no bearing on the topic at hand.  Unless the active includes silver, mercury (or lead) cations.

I could say, "The nitrate anion is a polyatomic anion, and the chloride ion is an ionized element."  That's a true statement, but it doesn't answer the question in any way.  You can stare at your statement or mine all day, but you'll never solve this problem that way.

5b) The intrinsic solubility of this drug is 1mcg/ml and the pKa is 2. Please estimate the solubility of the nitrate salt at the pH of the intestines (pH=6. by using mathematical or other approaches (4 marks)

A bit of pharmaceutical jargon here, and many steps left out.  This is a tough one as well.

>>>> Seems to be a mathematical problem, but doesn't provide enough info to do calculations?? I have got as far as the Henderson Hasselbach equation:

pH=pKa+log[A-]/[HA]
I know that the base has an intrinsic solubility of 1mcg/ml, and I assume I use this info to calculate at what pH this occurs, but how do I plug this value into the equation without any info on its molecular structure? And then how do I progress from there to the solubility of the nitrate salt??

I don't know if this line of reasoning will help you, or if as you note, we're missing information we need.

[Vidya]

Do you know the meaning of intrinsic solubility  or Buffered solubility  or thermodynamic solubility or  Unbuffered solubility?