Titre du document / Document title

The solubility of morphine and the stability of concentrated morphine solutions in glass, polypropylene syringes and PVC containers

Auteur(s) / Author(s)

VERMEIRE A. ⁽¹⁾ ; REMON J. P. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Laboratory of Pharmaceutical Technology, University of Gent, Harelbekestraat 72, 9000 Gent, BELGIQUE

Résumé / Abstract

Morphine solutions are frequently used in palliative settings for the treatment of severe cancer pain. There is, however, no complete information concerning the solubility, isotonisation and shelf-life of these solutions. The solubility limits of morphine hydrochloride (M) were determined as 50 mg/ml in water and 5% dextrose, and 30 mg/ml in 0.9% NaCl at 22°C, figures which decreased to 30 and 20 mg/ml, respectively at 4°C. Isotonisation of the M solutions with NaCl or dextrose did not cause any solubility problems at room temperature. The stability of isotonic M solutions and M solutions in water was investigated over a concentration range of 10-50 mg/ml. All solutions were stored in borosilicate glass, polypropylene syringes and PVC containers at 4, 22 and 40°C in the absence of light. Samples were taken immediately after preparation and after 1, 3, 7 and 14 days, 1, 2 and 3 months of storage. All samples were evaluated visually (colour and precipitation) and pH and osmolality were measured. Determination of morphine, morphine-N-oxide, pseudomorphine and apomorphine was done with a reversed-phase ion-pair HPLC assay. During storage at 4°C of M solutions at a concentration above 20 mg/ml, a white precipitate was formed that was difficult to redissolve. In all samples the pH and the osmolality remained nearly unchanged over the study period, except when stored in PVC containers at 22 and 40°C where there was a gradual increase of the osmolality during storage. In the solutions stored in PVC containers at 22 and 40°C an increase in M concentration of up to 105% of the theoretical concentration was detected after 1 month and I week, respectively. In all samples only two degradation products were found: morphine-N-oxide and pseudomorphine. During storage the concentration of both degradation products gradually increased, but remained below 0.4% for morphine-N-oxide and below 2% for pseudomorphine. The type of reservoir and the composition of the solution had only a minor influence on the degradation of M. This study indicates that concentrated M solutions are stable for 3 months under all conditions tested, but should be stored at 22°C to avoid precipitation.

Revue / Journal Title

International journal of pharmaceutics   ISSN 0378-5173   CODEN IJPHDE 

Source / Source

1997, vol. 146, n^o2, pp. 213-223 (24 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1978) (Revue)

Mots-clés anglais / English Keywords

Morphine ; Narcotic analgesic ; Physicochemical properties ; Solubility ; Storage stability ; Degradation product ; Shelf life ; Glass ; Borosilicates ; Syringe ; Propylene polymer ; Polyvinyl chloride ; Environmental factor ; Temperature ; Isotonic solution ; Opiates ; Container content interaction ;

Mots-clés français / French Keywords

Morphine ; Analgésique narcotique ; Propriété physicochimique ; Solubilité ; Stabilité stockage ; Produit dégradation ; Durée conservation ; Verre ; Borosilicate ; Seringue ; Propène polymère ; Vinylique chlorure polymère ; Facteur milieu ; Température ; Solution isotonique ; Opiacés ; Interaction contenant contenu ; Osmolalité ;

Mots-clés espagnols / Spanish Keywords

Morfina ; Analgésico narcotico ; Propiedad fisicoquímica ; Solubilidad ; Estabilidad al almacenamiento ; Producto degradación ; Tiempo conservación ; Vidrio ; Borosilicato ; Seringa ; Propeno polímero ; Vinílico cloruro polímero ; Factor medio ; Temperatura ; Solución isotónica ; Opiados ; Interacción continente contenido ;

Localisation / Location

INIST-CNRS, Cote INIST : 16510, 35400006448279.0080