Weighing tablets
 

Over the years a number of people have posted saying that their drugs have suddenly become less effective. Sometimes this has been linked to a move to generics. The suspicion has been that quality control has not been good enough.

I suspect that the effect of taking levodopa based drugs is especially affected by variations, both high or low, in the actual doses of the active component drugs. This could show itself in not crossing the "on"/"off" threshold or in increased dyskinesia. It could also be noticed in term of a dose wearing off earlier. On a three hour drug cycle a 5% lower dose would finish about 10 minutes earlier.

Ideally we could benefit from a full chemical analysis of each pill. But, not having the equipment to do that job, I thought we could make a start by accurately weighing tablets.

The whole weight of a tablet includes the filler, so you can't conclude that high figures are good and low figures are bad. Depending on the relative densities of the filler and the active ingredients, and possible oxidation going on, it could work either way. However, I think it is reasonable to expect a low variation in the tablet weights, both intra-batch and inter-batch.

The measurements below are raw (uncalibrated) weights (mg) of Stalevo tablets (levodopa 75, carbidopa 18.57, entacapone 200). 5 tablets were weighed from each of two batches. Each tablet (A to E) was weighed 3 times. The pills came from unopened plastic pill tubs, with a foil cover.

Batch 1742670
Expiry 04/2019
A, 530, 532, 531
B, 543, 544, 543
C, 538, 538, 537
D, 531, 530, 531
E, 521, 522, 524

Batch 1824362
Expiry 09/2020
A, 528, 526, 526
B, 519, 521, 520
C, 521, 521, 522
D, 526, 526, 524
E, 522, 522, 520

As a rough analysis, I will do a proper statistical analysis later, taking the middle result as the true weight of each pill and then taking the difference between the highest and lowest value gives:
Intra-batch
Batch 1742670, range = 21mg, about 4%
Batch 1824362, range = 6mg, about 1%
Inter-batch, range = 23mg, about 4%

As a calibration measure, though the above results use raw figures.

50 gm weight
Before 50149, 50148, 50144
After 50142, 50147, 50141

1p UK coin, nominal 3560
A, 3573, 3570, 3575
B, 3546, 3547, 3547
C, 3540, 3531, 3531

5p UK coin, nominal 3250
A, 3268, 3265, 3265
B, 3277, 3273, 3272
C, 3293, 3299, 3297
(The coins were not of mint condition.)

I used a digital scales, 8028 series. Available on eBay for about £10. If you want to look into this area, you want a scales that measures "0.001 g", i.e. a mg.

John

Hi John,
Thanks for starting this post.
My question to you and others is do any of you find opening a new bottle of tablets for PD works better with your symptoms?
I find with either Stalevo or Sinemet I feel better and have a better on when I've broken the seal and started taking new tablets.
At first I thought it was a coincidence however it seems to happen each time.
Now I'm more likely to be careful to know when I open e.g. a pill bottle I keep in my handbag for going out how old the tablets are.

Looking at generic products of Madopar (levodopa plus benserazide) which is similar to Sinemet (levodopa plus carbidopa), a group of researchers have found similar deviations in the weights of the active ingredients [1]:

"Each of the seven generic products had one or two parameters outside the specifications. Deviations for the active ingredients ranged from +8.4% (benserazide) to −7.6% (levodopa) in two tablet formulations."

John

Reference:

[1] "Pharmaceutical quality of seven generic Levodopa/Benserazide products compared with original Madopar/ Prolopa"
Urs E Gasser1, Anton Fischer , Jan P Timmermans and Isabelle Arnet
BMC Pharmacology and Toxicology 2013, https://bmcpharmacoltoxicol.biomedce...050-6511-14-24

if all i had to worry about was the weight of a tablet i'd be happy. but quality control is imho part of a serious and possibly life threatening problem for pd'ers who depend on C/L. The bigger potential problem is supply chain disruption caused by just a few manufacturers of active ingredients and possibly something used in CR which caused shortages last year. china may be the only supplier or active ingredients and now all the C/L manufacturers are from india except for mylan ([please correct me if i'm wrong). to add insult to injury, teva no longer manufactures C/L, they sold the rights or something to MAYNE pharmaceutical along with the ACTIVAS brand which TEVA owned. as far as i can tell, MAYNE does not manufacture the TEVA formula and uses the ACTIVAS formula. indian companies are not inspected nearly as often by the fda as american companies are, foreign inspection is more difficult to say the least.

i'm just ranting here but bottom line, if what i state here is true, write your congressman and demand that the govt either thru direct contracts or incentives makes sure there are least 2 manufacturers of carbidopa/levodopa in the u.s. and that there is at least a 1year stockpile. bottom line, drug mfg's want to make a lot of money, noone wants to sell a cheap drug. to let teva sell their generic to a company that didn't want to mfg it is sickening that deal makes no sense to me except MAYNE got rid of a competing generic.

fwiw, i fill my RX's at an independent pharmacy and they will sell me mylan 25/100, 25/250 and 50/200CR which costs more than the ACTIVIS brand. I pay thru the nose for the 50/200CR from mylan and it seems less effective. than it used to be.