Compatibility and stability of ternary admixtures of morphine with haloperidol or midazolam and dexamethasone or methylprednisolone

The concentration range over which compatible admixtures of morphine hydroc hloride with haloperidol lactate (Haldol(R)) or midazolam hydrochloride (Do rmicum(R)) and dexamethasone-21-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 at 22 degrees C. The compatibility was evaluated for admixtures prepared in a ratio morp hine hydrochloride (D-1)/drug 2 (D-2)/drug 3 (D-3) in a ratio 10/1/1 to 10/ 1/10 (v/v/v). The solutions of morphine hydrochloride used were 10, 20, 30, 40 and 50 mg/ml prepared in water and isotonized with sodium chloride or d extrose. The drug solutions were used undiluted and diluted 1/5 (v/v) in wa ter. All admixtures were prepared by adding the corticosteroid as D-2 and a s D-3 in order to evaluate the influence of the order of mixing on the comp atibility. The stability of the drugs in the compatible admixtures was eval uated during storage for 28 days at 22 degrees C and protected from light. Visual inspection, high performance liquid chromatography (HPLC) analysis, pH and osmolality determinations were performed. For each drug combination incompatibility was observed with increasing ratio and/or concentration of the drug solutions. Within the range of compatibility the concentrations of the three drugs could be increased so to allow adequate symptom control wi th all drug combinations. For a similar admixture a higher concentration of corticosteroid could be obtained using dexamethasone-21-sodium phosphate v ersus methylprednisolone-21-sodium succinate and a higher concentration of dexamethasone-21-sodium phosphate could be obtained without incompatibility using Decadron(R) Pack versus Decadron(R). The admixtures for which the st ability was evaluated were stable for 28 days (> 95% of the initial concent ration). None of these admixtures showed any visual changes during storage, except for some of the admixtures prepared using undiluted Decadron(R), in which small crystals were seen after 1-28 days. The initial pH of the admi xtures ranged from 3.99 to 6.06 and varied less than 0.10 during storage. T he initial osmolality of the admixtures ranged from 170 to 323 mOsm/kg and remained almost constant Juring storage. (C) 1999 Elsevier Science B.V. All rights reserved.