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4116379 
Journal Article 
Compatibility and stability of morphine in binary admixtures with haloperidol, midazolam, dexamethasone or methylprednisolone 
Vermeire, A; Remon, JP 
1998 
Yes 
International Journal of Pharmaceutics
ISSN: 0378-5173
EISSN: 1873-3476 
IPA/99/1180255 
174 
1-2 
157-177 
English 
WOS:000077008700019 
The concentration range over which compatible admixtures of morphine hydrochloride with haloperidol lactate (Haldol(R)), midazolam hydrochloride (Dormicum(R)), dexamethasone sodium phosphate (Decadron(R) and Decadron(R) Pack) or methylprednisolone-21-sodium succinate (Solu-Medrol(R)) can be prepared was determined by Visual evaluation of the solutions. Compatibility was investigated either by mixing the drug solution with the morphine hydrochloride solution or by adding morphine hydrochloride powder to the drug solution. The precipitate and the supernatant in the incompatible admixtures were analyzed by high performance liquid chromatography (HPLC) and NMR. The stability of the drugs in the compatible admixtures and of the drug solutions used to prepare the admixtures was evaluated during storage for 28 days at 22 degrees C and protected from light. Visual inspection, HPLC analysis, pH and osmolality determinations were performed. Addition of Dormicum(R), Haldol(R) or Decadron(R) (Pack) to the morphine hydrochloride solution (50 mg/ml) resulted in compatible admixtures up to a volume ratio drug/morphine hydrochloride: 10/10, 5/10, 1/10 (v/v), respectively. Addition of methylprednisolone (100 mg/ml) to the morphine hydrochloride solution (50 mg/ml) resulted in an incompatible admixture in a volume ratio drug/morphine hydrochloride: 1/10 (v/v). Inverting the order of mixing resulted in incompatibility for admixtures that were compatible when prepared by the addition of drug solution to the morphine hydrochloride solution, except for the admixtures prepared with Dormicum(R) for which the order of mixing did not affect compatibility. The concentration range over which compatibility was observed could not be extended by using the powder addition technique, except for the admixtures with Dormicum(R). The maximal amount of morphine hydrochloride that could be dissolved in Dormicum(R) was 30 mg/ml and increased to 50 mg/ml in its dilution 1/10 (v/v). For all admixtures tested no visual incompatibility was observed during the period studied, except for the admixtures prepared with undiluted Decadron(R) (Pack) solutions in which occasionally precipitation occurred. HPLC analysis revealed that all drugs remained stable (<10% degradation) in the admixtures and drug solutions studied, except for methylprednisolone-21-sodium succinate and dexamethasone sodium phosphate in the admixtures prepared using Decadron(R). (C) 1998 Elsevier Science B.V. All rights reserved. 
dexamethasone sodium phosphate; haloperidol lactate; incompatibility; methylprednisolone sodium succinate; midazolam hydrochloride; morphine hydrochloride; stability