COMPATIBILITY AND STABILITY OF MORPHINE IN BINARY ADMIXTURES WITH HALOPERIDOL, MIDAZOLAM, DEXAMETHASONE OR METHYLPREDNISOLONE

The concentration range over which compatible admixtures of morphine h ydrochloride with haloperidol lactate (Haldol(R)), midazolam hydrochlo ride (Dormicum(R)), dexamethasone sodium phosphate (Decadron(R) and De cadron(R) Pack) or methylprednisolone-21-sodium succinate (Solu-Medrol (R)) can be prepared was determined by Visual evaluation of the soluti ons. Compatibility was investigated either by mixing the drug solution with the morphine hydrochloride solution or by adding morphine hydroc hloride powder to the drug solution. The precipitate and the supernata nt in the incompatible admixtures were analyzed by high performance li quid chromatography (HPLC) and NMR. The stability of the drugs in the compatible admixtures and of the drug solutions used to prepare the ad mixtures was evaluated during storage for 28 days at 22 degrees C and protected from light. Visual inspection, HPLC analysis, pH and osmolal ity 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 met hylprednisolone (100 mg/ml) to the morphine hydrochloride solution (50 mg/ml) resulted in an incompatible admixture in a volume ratio drug/m orphine hydrochloride: 1/10 (v/v). Inverting the order of mixing resul ted in incompatibility for admixtures that were compatible when prepar ed by the addition of drug solution to the morphine hydrochloride solu tion, except for the admixtures prepared with Dormicum(R) for which th e order of mixing did not affect compatibility. The concentration rang e over which compatibility was observed could not be extended by using the powder addition technique, except for the admixtures with Dormicu m(R). The maximal amount of morphine hydrochloride that could be disso lved in Dormicum(R) was 30 mg/ml and increased to 50 mg/ml in its dilu tion 1/10 (v/v). For all admixtures tested no visual incompatibility w as observed during the period studied, except for the admixtures prepa red 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 studie d, except for methylprednisolone-21-sodium succinate and dexamethasone sodium phosphate in the admixtures prepared using Decadron(R). (C) 19 98 Elsevier Science B.V. All rights reserved.