Furthering the debate on bioavailability of morphine

[methologist]

Swim read on a few pages that morphine rectally is basically the same bioavailability as oral morphine... yeah it sux i know...

Here is something else swim found...

In 7 volunteers Verweij and van Gijn studied the pharmacokinetics of morphine after 4 puffs of about 100 µl (2 times 1 puff of 100, µl in each nostril). The exact dose which was delivered to the volunteers was 16 mg of morphine (range 15-18 mg) and the bioavailability of morphine from this nasal spray was 26-35%. The bioavailabilty of morphine after oral application is estimated to be about 40% (J. Sawe, Clin. Pharmacokinetics 1986; 11: 87-106). This means, that the bioavailability of morphine after giving the nasal spray as described by Verweij and van Gijn is relatively low. After nasal absorption there is no first pass effect and therefore the nasal bioavailability should be higher than the oral.

The nasal absorption of morphine has been studied also by F Chast et al (J. Pharm. Clin. 1992; 11: 257-261 ). They delivered nasally and orally 20 mg morphine acetate in an aqueous solution to 6 patients and compared the nasal absorption with the oral absorption of the same solution. They found, as expected, higher blood levels of morphine after the nasal application. Unfortunately, the nasal solutions, as described by the preceding studies of Verweij and van Gijn and of Chast and coworkers, are not stable and the bioavailability of morphine can be improved.

An object of the invention is to provide a highly stable pharmaceutical composition, suitable for nasal administration, and showing an superior bioavailability of morphine.

According to the invention, the nasal pharmaceutical composition contains morphine and/or morphine salts (hydrochloride, sulphate, acetate) and a cyclodextrin and/or other saccharides and/or sugar alcohols. Such compositions appear to result in a surprisingly high bioavailability and superior stability of morphine.




If you look at the last part, it seems that when morphine hcl or sulphate is mixed with a cyclodextrin, [or im wondering if Maltodextrine (splenda) can be used], that it gives a very high bioavailability.

So mixing these 2 in a water solution and spraying it up the nose might give a better chance of potentiating the morphine from pills?


Here is another find swim found...

"Morphine ~30% oral/rectal, insuffulated- 15-20%,"


Also found this statement which says if one eats a high fat meal before hand it increases bioavailability 34%...hell swim wants a big piece of chicken with his morphine now!

Food: Administration of oral morphine solution with food may increase bioavailability (ie, a report of 34% increase in morphine AUC when morphine oral solution followed a high-fat meal). The bioavailability of Oramorph SR® does not appear to be affected by food.











Now below there is discussion that tells how to make sniffing morphine just as effective or close to as effective as IV morphine...

This is the most promising thing ive found


Intranasal Delivery of Morphine


L. Illum, P. Watts, A. N. Fisher, M. Hinchcliffe, H. Norbury, I. Jabbal-Gill, R. Nankervis and S. S. Davis
West Pharmaceutical Services, Drug Delivery and Clinical Research Centre Ltd., Albert Einstein Centre, Nottingham Science and Technology Park, Nottingham, United Kingdom

"Morphine administered nasally to humans as a simple solution is only absorbed to a limited degree, with a bioavailability of the order of 10% compared with intravenous administration. This article describes the development of novel nasal morphine formulations based on chitosan, which, in the sheep model, provide a highly increased absorption with a 5- to 6-fold increase in bioavailability over simple morphine solutions. The chitosan-morphine nasal formulations have been tested in healthy volunteers in comparison with a slow i.v. infusion (over 30 min) of morphine. The results show that the nasal formulation was rapidly absorbed with a Tmax of 15 min or less and a bioavailability of nearly 60%. The shape of the plasma profile for nasal delivery of the chitosan-morphine formulation was similar to the one obtained for the slow i.v. administration of morphine. Furthermore, the metabolite profile obtained after the nasal administration of the chitosan-morphine nasal formulation was essentially identical to the one obtained for morphine administered by the intravenous route. The levels of both morphine-6-glucuronide and morphine-3-glucuronide were only about 25% of that found after oral administration of morphine. It is concluded that a properly designed nasal morphine formulation (such as one with chitosan) can result in a noninjectable opioid product capable of offering patients rapid and efficient pain relief."


Chitosan is very much over the counter too!

[helikophis]

Sorry to resurrect an old thread. After reading this article, some poking around on the forum turned up a few references to chitosan and its effect on morphine, but no practical comments on the combination, just questions. Is anyone aware of anyone other than these researchers who has produced a nasal preparation with morphine and chitosan?

Any ideas on how someone would go about doing this? It seems like it could be a very popular combination, if a technique were developed. Do people think it would be effective to simply combine morphine sulfate powder with bulk chitosan powder, and insufflate the mixture? Better to make a solution and insufflate that? Or neither? Any ideas?

I would have started a thread with chitosan and morphine in the title, but since it is mentioned in several threads already, I guess this one will do.

[Mike177]

Originally Posted by helikophis

Sorry to resurrect an old thread. After reading this article, some poking around on the forum turned up a few references to chitosan and its effect on morphine, but no practical comments on the combination, just questions. Is anyone aware of anyone other than these researchers who has produced a nasal preparation with morphine and chitosan?

Any ideas on how someone would go about doing this? It seems like it could be a very popular combination, if a technique were developed. Do people think it would be effective to simply combine morphine sulfate powder with bulk chitosan powder, and insufflate the mixture? Better to make a solution and insufflate that? Or neither? Any ideas?

I would have started a thread with chitosan and morphine in the title, but since it is mentioned in several threads already, I guess this one will do.

Hello helikophis,
SWIM was actually planning on doing some research into this topic in a week or so when SWIM's work load lightens up. SWIM noticed that the abstract to the article was referenced, but SWIM did not see any posts of the whole article. Last night SWIM decided to upload the article the forum so those who would like to read their materials and methods could. SWIM has not read the entire article yet, but will in a week or two. Hopefully SWIM can summarize the article for the users here, especially the part about preparation and concentrations of the formulations. SWIM may even do an experiment of his own with the formulations given in the article. However it will have to wait for a week due to SWIM's current obligations.

Here is a link to the article in its entirety: http://www.drugs-forum.com/forum/loc...tid=24&id=6881 . SWIM is not aware of other articles about the same subject matter; however that is not to say they don't exist. SWIM just has not seen them. SWIM will do some journal searching and report back if he finds anything. SWIM is lucky in that he has free access to may journals. Hope this helps you out!

Mike

Update: I have found a few more articles relating to this subject, I will try to get them up in a few days.

[helikophis]

Originally Posted by Mike177

Hello helikophis,
SWIM was actually planning on doing some research into this topic in a week or so when SWIM's work load lightens up. SWIM noticed that the abstract to the article was referenced, but SWIM did not see any posts of the whole article. Last night SWIM decided to upload the article the forum so those who would like to read their materials and methods could. SWIM has not read the entire article yet, but will in a week or two. Hopefully SWIM can summarize the article for the users here, especially the part about preparation and concentrations of the formulations. SWIM may even do an experiment of his own with the formulations given in the article. However it will have to wait for a week due to SWIM's current obligations.

Here is a link to the article in its entirety: http://www.drugs-forum.com/forum/loc...tid=24&id=6881 . SWIM is not aware of other articles about the same subject matter; however that is not to say they don't exist. SWIM just has not seen them. SWIM will do some journal searching and report back if he finds anything. SWIM is lucky in that he has free access to may journals. Hope this helps you out!

Mike

Update: I have found a few more articles relating to this subject, I will try to get them up in a few days.

Yes I'd seen that the whole article was posted and looked it over; that was what starting my poke around. It will be interesting to hear how SWIY's experiments go, and the further articles you've found. Thanks!