Dataset Information

The Physicochemical Compatibility of Sildenafil Injection with Parenteral Medications Used in Neonatal Intensive Care Settings.

ABSTRACT: Sildenafil is used to treat pulmonary hypertension in neonatal intensive care unit (NICU) settings. As multiple intravenous (IV) medications are co-administered in NICU settings, we sought to investigate the physicochemical compatibility of sildenafil with a range of IV drugs. Sildenafil 600 mcg/mL or 60 mcg/mL was mixed 1:1 with the secondary drug solution to simulate Y-site co-administration procedures. Physical compatibility was evaluated by visual observation against a black and white background and under polarized light for two hours for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from sildenafil concentrations, using a validated, stability-indicating high-performance liquid chromatography assay. Sildenafil 600 mcg/mL was physicochemically compatible with 29 of the 45 drugs tested at 'high-end' clinical concentrations and physically incompatible with 16 drugs and six '2-in-1' parenteral nutrition solutions. Sildenafil 600 mcg/mL was compatible with lower, clinically relevant concentrations of calcium gluconate, heparin and hydrocortisone. Aciclovir, amoxicillin, ampicillin, ibuprofen lysine, indometacin, phenobarbitone and rifampicin were incompatible with sildenafil 600 mcg/mL, however these IV medications were compatible with sildenafil 60 mcg/mL. Sildenafil 600 mcg/mL and 60 mcg/mL were incompatible with amphotericin, flucloxacillin, furosemide, ibuprofen, meropenem and sodium bicarbonate. Sildenafil compatibility with commonly used syringe filters was also investigated. Sildenafil solution was compatible with nylon syringe filters, however, absorption/adsorption loss occurred with polyethersulfone and cellulose ester filters.

SUBMITTER: De Silva DTN

PROVIDER: S-EPMC10974670 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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The Physicochemical Compatibility of Sildenafil Injection with Parenteral Medications Used in Neonatal Intensive Care Settings.

De Silva D Thisuri N DTN Strunk Tobias T Petrovski Michael M Page-Sharp Madhu M Moore Brioni R BR Batty Kevin T KT

Pharmaceutics 20240318 3

Sildenafil is used to treat pulmonary hypertension in neonatal intensive care unit (NICU) settings. As multiple intravenous (IV) medications are co-administered in NICU settings, we sought to investigate the physicochemical compatibility of sildenafil with a range of IV drugs. Sildenafil 600 mcg/mL or 60 mcg/mL was mixed 1:1 with the secondary drug solution to simulate Y-site co-administration procedures. Physical compatibility was evaluated by visual observation against a black and white backgr ...[more]

PMID: 38543312

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Project description:BackgroundRecombinant human (rh)IGF-1/IGFBP-3 protein complex, administered as a continuous intravenous infusion in preterm infants, is being studied for the prevention of complications of prematurity.MethodsWe conducted in vitro studies to evaluate the physical and chemical compatibility of rhIGF-1/IGFBP-3 with medications routinely administered to preterm neonates. In vitro mixing of rhIGF-1/IGFBP-3 drug product with small-molecule test medications plus corresponding controls was performed. Physical compatibility was defined as no color change, precipitation, turbidity, gas evolution, no clinically relevant change in pH/osmolality or loss in medication content. Chemical compatibility of small molecules was assessed using liquid chromatography (e.g., reverse-phase HPLC and ion chromatography), with incompatibility defined as loss of concentration of ≥ 10%. A risk evaluation was conducted for each medication based on in vitro compatibility data and potential for chemical modification.ResultsIn vitro physical compatibility was established for 11/19 medications: caffeine citrate, fentanyl, fluconazole, gentamicin, insulin, intravenous fat emulsion, midazolam, morphine sulfate, custom-mixed parenteral nutrition solution (with/without electrolytes), parenteral nutrition solution + intravenous fat emulsion, and vancomycin (dosed from a 5 mg/mL solution), but not for 8/19 medications: amikacin, ampicillin, dopamine, dobutamine, furosemide, meropenem, norepinephrine, and penicillin G, largely owing to changes in pH after mixing. Small-molecule compatibility was unaffected post-mixing, with no loss of small-molecule content. For physically compatible medications, risk analyses confirmed low probability and severity of a risk event.ConclusionCo-administration of rhIGF-1/rhIGFBP-3 drug product with various medications was assessed by in vitro studies using case-by-case risk analyses to determine the suitability of the products for co-administration.

Project description:BackgroundPrevious studies of compatibility of calcium chloride (CaCl2) and phosphates have not included particle counts in the range specified by the United States Pharmacopeia. Micro-flow imaging techniques have been shown to be comparable to light obscuration when determining particle count and size in pharmaceutical solutions.ObjectiveThe purpose of this study was to do compatibility testing for parenteral nutrition (PN) solutions containing CaCl2 using dynamic light scattering and micro-flow imaging techniques.MethodsSolutions containing TrophAmine (Braun Medical Inc, Irvine, CA), CaCl2, and sodium phosphate (NaPhos) were compounded with and without cysteine. All solutions contained standard additives to neonatal PN solutions including dextrose, trace metals, and electrolytes. Control solutions contained no calcium or phosphate. Solutions were analyzed for particle size and particle count. Means of Z-average particle size and particle counts of controls were determined. Study solutions were compared to controls and United States Pharmacopeia (USP) Chapter 788 guidelines. The maximum amount of Phos that was compatible in solutions that contained at least 10 mmol/L of Ca in 2.5% amino acids (AA) was determined. Compatibility of these solutions was verified by performing analyses of 5 repeats of these solutions. Microscopic analyses of the repeats were also performed.ResultsAmounts of CaCl2 and NaPhos that were compatible in solutions containing 1.5%, 2%, 2.5%, and 3% AA were determined. The maximum amount of NaPhos that could be added to TrophAmine solutions of > = 2.5% AA containing at least 10 mmol/L of CaCl2 was 7.5 mmol/L. Adding 50 mg/dL of cysteine increased the amount of NaPhos that could be added to solutions containing 10 mmol/L of CaCl2 to 10 mmol/L.ConclusionCalcium chloride can be added to neonatal PN solutions containing NaPhos in concentrations that can potentially provide an intravenous intake of adequate amounts of calcium and phosphorus.

Dataset Information

The Physicochemical Compatibility of Sildenafil Injection with Parenteral Medications Used in Neonatal Intensive Care Settings.

Publications

The Physicochemical Compatibility of Sildenafil Injection with Parenteral Medications Used in Neonatal Intensive Care Settings.

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