If Euhydric and Isotonic Do Not Work, What Are Acceptable pH and Osmolality for Parenteral Drug Dosage Forms?

Roethlisberger, Dieter; Mahler, Hanns‐Christian; Altenburger, Ulrike; Pappenberger, Astrid

doi:10.1016/j.xphs.2016.09.034

Cited by 59 publications

(40 citation statements)

References 42 publications

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“…The osmolality study indicated that the reconstituted solutions with WFI (as recommended in SmPC20 at 40–60 and 80 mg/mL) remained very hypotonic in 50 mL syringes, and consequently could not be injected to patients due to an osmolality inferior to 154 mOsmol/kg 21. Infusion of hypotonic solutions is associated with an increase in hyponatraemia22 and can lead to cellular necrosis.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the stability of vancomycin solutions at concentrations used in clinical services

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Evaluation of the stability of vancomycin solutions at concentrations used in clinical services

et al. 2020

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“…The parenteral product should be isotonic and euhydric (physiological pH) to avoid local damage on the vascular endothelium and circulating blood cells. 38 Incorporation of the small amount of glycerol assisted in generating emulsion with osmolality value that is close to the normal osmotic pressure at physiological pH (280-320 mOsm/kg). The addition of 2.3% of glycerol (w/w) has significantly increased the osmolality value of CLN to 285.33±0.58 mOsm/kg, the value that was isotonic to blood.…”

Section: Viscosity and Osmolality Analysesmentioning

confidence: 99%

Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: designs, characterizations, and pharmacokinetics

Harun¹,

Nordin²,

Gani³

et al. 2018

IJN

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Background and aimDrugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood–brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered.MethodsThe nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties.ResultsThe characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of −46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0–t, prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0–t, prolonged half-life, and lower clearance as compared to free cefuroxime solution.ConclusionOverall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.

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“…Osmolality values for the CNPEG, CP21, CP23, CP51 and CP53 were 556, 555, 531, 562 and 543 mOsm/kg, respectively. This would indicate good tolerability upon parenteral administration, as osmolality values higher than 600 mOSm/kg have been reported to cause shriveling up of red blood cells and significant pain, while osmolality values less than 150 mOsm/kg may cause hemolysis [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

Curcumin Loaded PEGylated Nanoemulsions Designed for Maintained Antioxidant Effects and Improved Bioavailability: A Pilot Study on Rats

Đoković

Savić²,

Mitrović

et al. 2021

IJMS

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The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.

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If Euhydric and Isotonic Do Not Work, What Are Acceptable pH and Osmolality for Parenteral Drug Dosage Forms?

Cited by 59 publications

References 42 publications

Evaluation of the stability of vancomycin solutions at concentrations used in clinical services

Evaluation of the stability of vancomycin solutions at concentrations used in clinical services

Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: designs, characterizations, and pharmacokinetics

Curcumin Loaded PEGylated Nanoemulsions Designed for Maintained Antioxidant Effects and Improved Bioavailability: A Pilot Study on Rats

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