Background So far compatibilities between two proprietary medicines have been tested in the lab.
A plethora of publications exists and contradictory results are inevitable.
Uncertainties remain if a specific compound has not yet been tested.
To present a model imaging the mechanism (s) to achieve stable mixtures of two proprietary medicines in NaCl 0.9%, administered by y-site.
Including all ingredients.
To assess a physicochemical background defined by a minimum of criteria.
To guarantee traceability of the results using publicly accessible data.
To enable predictions
Material and methods
Physicochemical data were retrieved from databases: Drugbank, ChemSpider, oddb.org and swissmedicinfo.ch
Trissel and KingGuide were used as authorities of compatibility samples.
Material and methodsA pilot study creating a decision tree (DTREG software) revealed the factors influencing compatibilities: pH ranges of drug solutions (pHr), polar surface areas (PSA), solvent accessible surface areas (SASA), log P, pKa values, molecular polarisability (mPOL) and inorganic ions.
Results Supervising these results prompted us to look at any characteristics of polarities: ionic bonds, (induced) dipoles, H bonds determining water structures.
Standing out were the pH ranges of the drug solutions and the potential polarisation of the apolar area of the active substance (pPol):
Compatible mixtures exhibit pH and mPol ranges consistent with the water structure indicated by inorganic ions and supplemental ingredients.
So far we analysed around 200 mixtures of two proprietary medicines. All results are in agreement with the literature.
Conclusion The proposed model allows us to discriminate compatible iv admixtures for small drug molecules. The process is straightforward and most of the data required are publicly accessible.
An internet platform will be published in the near future containing pPol values of the commonly used active ingredients.
The validity of the present model is restricted by the calculus used to estimate the values of the molecular surfaces and their polarisabilities. Molecular weights are limited to about 3000 Da.
References and/or Acknowledgements For references see materials section
Many thanks to the colleagues who provided critical arguments and/or ambiguous compatibility results.
No conflict of interest.
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