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 hydrochloride with haloperidol lactate (Haldol) or midazolam hydrochloride (Dormicum) and dexamethasone-21-sodium phosphate (Decadron and Decadron Pack) or methylprednisolone-21-sodium succinate (Solu-Medrol) 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 morphine hydrochloride (D1)/drug 2 (D2)/drug 2 (D3) 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 dextrose. The drug solutions were used undiluted and diluted 1/5 (v/v) in water. All admixtures were prepared by adding the corticosteroid as D2 and as D3 in order to evaluate the influence of the order of mixing on the compatibility. The stability of the drugs in the compatible admixtures was evaluated 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 with all drug combinations. For a similar admixture a higher concentrations of corticosteroid could be obtained using dexamethasone-21-sodium phosphate versus methylprednisolone-21-sodium succinate and a higher concentration of dexamethasone-21-sodium phosphate could be obtained without incompatibility using Decadron Pack versus Decadron. The admixtures for which the stability was evaluated were stable for 28 days (> 95% of the initial concentration). None of these admixtures showed any visual changes during storage, except for some of the admixtures prepared using undiluted Decadron, in which small crystals were seen after 1-28 days. The initial pH of the admixture ranged from 3.99 to 6.06 and varied less than 0.10 during storage. The initial osmolality of the admixtures ranged from 170 to 323 mOsm/kg and remained almost constant during storage.
Vermeire
A
A
Laboratory of Pharmaceutical Technology, University of Gent, Belgium.
Remon
J P
JP
D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000737:chemistry*; D004344:Drug Incompatibility; D004355:Drug Stability; D006220:Haloperidol / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008775:Methylprednisolone / Q000737:chemistry*; D008874:Midazolam / Q000737:chemistry*; D009020:Morphine / Q000737:chemistry*; D009994:Osmolar Concentration; D012995:Solubility; D013696:Temperature
D009020:Morphine; D003907:Dexamethasone; D006220:Haloperidol; D008874:Midazolam; D008775:Methylprednisolone