jag009
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NJ,
2012-05-31 01:35
(5127 d 08:04 ago)

Posting: # 8638
Views: 19,684
 

 Adderall: why 4 salts of Amphetamine? [Off Topic]

Hi all,

Why are there 2 different salts of D and L amphetamine in Adderall? D is more potent than L but what is the rationale for the two different salts?

The only thing I can think of is to play around with solubility and the absorption rates.

Thanks

John
Helmut
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Vienna, Austria,
2012-05-31 03:38
(5127 d 06:01 ago)

@ jag009
Posting: # 8639
Views: 17,452
 

 Adderall: why 4 salts of Amphetamine?

Dear John!

❝ Why are there 2 different salts of D and L amphetamine in Adderall?


Neither 2 nor 4 but 3 (sulfate, saccharate, aspartate):
  • ¼ d-amphetamine saccharate
  • ¼ d-amphetamine sulfate
  • ¼ d/l-amphetamine sulfate (=racemate)
  • ¼ d/l-amphetamine aspartate monohydrate (=racemate)
The isomeric ratio d/l is ≈3:1 (different molecular masses of the salts). BTW, I never could reproduce the ‘total amphetamine base equivalence’ given in Adderall XR’s label…

❝ D is more potent than L …


In most patients. Some showed better response to this weird mixture.*

❝ … but what is the rationale for the two different salts?


Good question.

❝ The only thing I can think of is to play around with solubility and the absorption rates.


Hhm. Amphetamine is highly soluble (BCS III, cLogP 1.285, logP 1.680) and almost completely absorbed. The anions are irrelevant. At least the price of d-amphetamine sulfate is astronomical. Maybe other salts are cheaper? ;-)


  • LE Arnold
    Methylphenidate vs. amphetamine: Comparative review
    Journal of Attention Disorders 3, 200–11 (2000)

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jag009
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NJ,
2012-05-31 20:02
(5126 d 13:37 ago)

@ Helmut
Posting: # 8646
Views: 17,375
 

 Adderall: why 4 salts of Amphetamine?

Thanks guys,

Another question.

When you do potency on this product (adderall XR), do you have to perform potency testing on the D and L separately (since it's 3:1 ratio) when compare between a test and reference? You know, the 5% rule...

Thanks

John
Helmut
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Vienna, Austria,
2012-05-31 20:11
(5126 d 13:27 ago)

@ jag009
Posting: # 8647
Views: 17,374
 

 Adderall: why 4 salts of Amphetamine?

Dear John!

❝ When you do potency on this product (adderall XR), do you have to perform potency testing on the D and L separately (since it's 3:1 ratio) when compare between a test and reference? You know, the 5% rule...


Yep. Your product may be different in isomeric composition. Three years ago we found in Dexedrine [sic] ~4% l-amphetamine and in the test product (likely another supplier of the API) only 0.6%…

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jag009
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NJ,
2014-02-28 18:00
(4488 d 14:38 ago)

@ Helmut
Posting: # 12530
Views: 16,302
 

 Amphetamine BCS?

Hi Helmut,

old topic...

❝ Hhm. Amphetamine is highly soluble (BCS III, cLogP 1.285, logP 1.680) and almost completely absorbed. The anions are irrelevant. At least the price of d-amphetamine sulfate is astronomical. Maybe other salts are cheaper? ;-)


Any idea where I can find info about amphetamine being BCS III?

Thanks

John
Helmut
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2014-02-28 18:12
(4488 d 14:26 ago)

@ jag009
Posting: # 12531
Views: 16,591
 

 Amphetamine BCS?

Hi John,

❝ Any idea where I can find info about amphetamine being BCS III?


I got the quoted values from TSRL’s BCS-Resources. Click “Access BCS Classification System Now“ (the direkt link changes almost monthly…).

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AngusMcLean
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USA,
2014-02-28 19:29
(4488 d 13:10 ago)

@ jag009
Posting: # 12534
Views: 16,291
 

 Amphetamine BCS?

The salts are very soluble, but the free base is an oil and is of course not as soluble.

I think a salt of amphetamine is Class 1 BCS, highly soluble and highly permeable, since it is completely absorbed.

ANGUS
Dr_Dan
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Germany,
2012-05-31 12:12
(5126 d 21:27 ago)

@ jag009
Posting: # 8641
Views: 17,387
 

 Adderall: why 4 salts of Amphetamine?

Hi John
The rationale for different salts is in most cases patent circumvention strategies, but I do not know if this is the case here.
Kind regards
Dan

Kind regards and have a nice day
Dr_Dan
AngusMcLean
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USA,
2014-02-28 19:18
(4488 d 13:20 ago)

@ jag009
Posting: # 12532
Views: 16,412
 

 Adderall: why 4 salts of Amphetamine?

The reason of formulating Adderall with mixed salts originally was to discourage generic companies from copying the product. The isomers nowadays are regarded as equipotent. I think it was originally for obesity.


Angus
AngusMcLean
★★  

USA,
2014-02-28 19:24
(4488 d 13:15 ago)

@ jag009
Posting: # 12533
Views: 16,207
 

 Adderall: why 4 salts of Amphetamine?

There is no scientific rationale; I am aware of one company that tested the salts against each other and they were BE.
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