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Arzneimittelforschung 2008; 58(12): 647-652
DOI: 10.1055/s-0031-1296566
Analgesics · Anti-inflammatories · Antiphlogistics · Antirheumatic Drugs
Editio Cantor Verlag Aulendorf (Germany)

In vitro and in vivo Studies of a New Sustained Release Formulation of Morphine

Discrepancies between the in vitro release and the in vivo absorption in dogs
Amparo Araíco
1   Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
,
Francisca Torres-Molina
1   Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
,
Anas Saadeddin
1   Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
,
Jaime Cárcel-Trullols
1   Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
,
Josefa Alvarez-Fuentes
2   Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Sevilla, Sevilla, Spain
,
Angeles Holgado
2   Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Sevilla, Sevilla, Spain
,
Mercedes Fernández-Arévalo
2   Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Sevilla, Sevilla, Spain
,
José-Esteban Peris
1   Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
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Publikationsverlauf

Publikationsdatum:
19. Dezember 2011 (online)

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Abstract

An in vivo preclinical study has been made of the oral absorption of morphine (CAS 57-27-2) from a new sustained release formulation (morphine-Eudragit® L complex, MEC), which had shown good sustained release properties in in vitro dissolution studies. The absorption of morphine from capsules filled with morphine hydrochloride trihydrate (MHT) or MEC was compared in fasted and fed dogs. Mean plasma morphine concentrations obtained after administration of MHT and MEC to fasted dogs were similar, and no statistically significant differences were found in the pharmacokinetic parameters of morphine (Cmax, Tmax and area under the plasma morphine concentration versus time curve from time zero to the last time with a detectable concentration of morphine). When MHT and MEC were administered to fed animals, mean plasma morphine concentrations were again similar for both formulations, without statistically significant differences in the pharmacokinetic parameters of morphine. These results contrast with those obtained in vitro, and indicate the limited usefulness of in vitro assays for this kind of sustained release formulations in which pH and ionic strength are important factors for drug release from the polymeric structure. The plasma morphine concentrations obtained in fed dogs were generally lower than in fasted dogs, though they were detectable for a longer time, until 10 h after dosing, in contrast to up to 6 h in fasted dogs. It is postulated that the apparently prolonged absorption of morphine in fed dogs may be due to the enterohepatic recycling of the drug (excreted in bile as glucuronide, hydrolysed back to the parent compound in the intestine, and then reabsorbed) as a consequence of gallbladder emptying induced by food.

Key words

Analgesics, opioid - CAS 57-27-2 - Eudragit® L, morphine formulation - Morphine, dog, pharmacokinetics, sustained release formulation - Morphine-Eudragit® L complex
 

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