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Pharmacy/Extended release medication


QUESTION: Hello Doctor.  My mother, age 89, has taken the medication Aggrenox for 10 years.  (Generic name is dipyridamole, in combination with aspirin.)  It is used every 12 hours as an antiplatelet to prevent stroke.  It is a capsule that contains a small aspirin tablet, and also many tiny units of dipyridamole.  My mother can no longer swallow the capsule.  A pharmacist had told me that the capsule could be opened, the aspirin tablet could be crushed, but not to crush the dipyridamole units.  Then add it all to something for her to drink.  More recently I've read that the capsule should never be opened.  Opening it can cause the release of too much medication at one time.  I would like to know how the dipyridamole units are made, and how the medication is released over time.   And in general, not just for this particular medication, I wonder how the extended release works.  Since I have no education in this subject, I would assume that not all of the units of each medication are created equally, and that maybe some units have more protective coating than others so that they take longer to become active.  But they are all within the same capsule.  Is there a fairly simple way to explain it to those of us not trained in this subject?   I wonder if the manufacturer of the Aggrenox capsules states that they should never be opened only as a precaution in case the medication might be crushed?  Or is it safe to open the capsule but not crush the dipyridamole inside?    Thank you very much.

ANSWER: Hi Vicki,
Sorry for the delay  in replying. I was out  of town and not carrying my laptop. The product you are asking about is Aggrenox which contains dipyridamole and aspirin. The capsule contains a tab  of aspirin 25 mg and dipyridamole 200mg in a sustained release form.  The yellow colored pellets contain dipyridamole in a sustained release (SR) form. The product is of Behringer Ingelheim, who have the best technology in  this form of drugs.

SR formulations are of various types, the  one used in  Aggrenox uses the  pellet technology. In  this technology the following method  is employed.

Pellets of the drug are prepared using wax like substances, and they are usually  made in four  or five lots. Each  lot has  a different dissolution pattern, so that one  dissolves in 5 hours, another dissolves in 10 hours, one in 15 hours and one in 20 hours (this is an example).
Then  the  four lots are thoroughly mixed so that the mixture contains an equal number of the  four  types of pellets. These are  packed in capsules with  a tablet of aspirin.

Theoretically when a capsule is  ingested, it  breaks  open in 30 min in the  stomach. The fastest dissolving pellets start releasing the  drug, and one after another each type  of pellets continue  to pour  the drug into  the system. Hopefully we get  a slow release over a  period of 20 hours
The effects of  dipyridamole are short lived while those of aspirin are very long term. With  this formulation the patients gets protection from platelet aggregation  (which can  cause strokes) for over  20 to 24 hours the capsule may be used once a day (or twice if the need be).

So  what precautions should one take while taking this drug:

1. Take the  capsule whole.
2. You  may open the capsule, but do not crush the pellets, the sustained release technology goes waste if  the pellets are crushed, you may also get side effects due  to dumping of  the drug.
3. If you open  the capsule, do not  dissolve the pellets before taking them, however you may pour the  pellets over  a porridge but  again do not  crush  the pellets  while chewing.

I do hope I  have been  able  to explain  in a simple  way. But if you  have doubts, please get back to me without hesitation.

All the best

Ravi Ghooi

---------- FOLLOW-UP ----------

QUESTION: Thank you so very much for your reply, which was very prompt.  No delay at all!  I am very grateful that you help people with your knowledge.
Since my mother cannot swallow the capsules, it does seem fairly safe to open the capsules, as long as the contents aren't crushed.  The problem of dose dumping only happens with crushing, not merely opening the capsule, if I understand correctly.    Again, many thanks for your help.

Hi Vicki,
I am glad that I have  been clear enough. Many  experts will warn against opening a  capsule,  without realizing that the capsule itself plays no  role in  controlling the  release of  drugs. The age and  difficulty of  the patient has to  be considered,  in laying down ground rules.
Please convey my best wishes to your mother. My mother would have been of  the same  age  had  she survived till today.
All the best


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Dr. Ravindra Bhaskar Ghooi


I can provide information on drugs and medicines, their actions, uses, interactions and adverse effects. To avoid confusion, generic names of medicines may please be provided. I am a pharmacologist, having worked on animal and human pharmacology, and presently I am the Dean of Bilcare Research Academy, where we teach courses on clinical research. We dont work on saturdays and sundays, hence questions reachng me on these days will be replied on Monday, please bear with me.

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