Partial molal volumes and solubilities of physostigmine in isopropanol:isopropyl myristate solvents in relation to skin penetrability

Asher Pardo, Yoseph Shiri, Sasson Cohen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Partial molal volumes (V i∞) of physostigmine, ranging from 232.9 to 239.8 cm3 · mol−1, and its mole fraction solubilities (Xi), ranging from 0.051 to 0.009, were determined at 25 °C in solutions of isopropanol (IPA), isopropyl myristate (IPM), and their mixtures. An inverse relation was found between V i∞ and Xi. At solubility →; O, V i∞ → 240.6 (by extrapolation). The experimentally derived liquid molal volume in the standard state, V i∞ (231.1), of physostigmine was lower than its lowest Vi (value 232.9) in the series tested. Virtual cohesion parameters (Λ) and excess free energies (ΔEGi) of physostigmine in the various solutions were estimated from the partial molal volumes, assuming regular solution behavior. For each solution, the free energy (‐RT In Xi) of the drug was estimated from its solubility. An increase in the virtual cohesion parameter and a decrease in the excess free energy and the free energy was found with an increase in volume fraction of IPA in the mixed solvent. The increase in Λi over the invariant cohesion parameter, δi (10.2), reflects a compensation effect needed to maintain the geometric mean assumption of Regular Solution Theory. Deviation from the theoretically expected linearity between ‐RT In Xi and ΔEGi of physostigmine is ascribed to the existence of solvated molecules distinct from unsolvated molecules of physostigmine. The highest permeability coefficient of the delivery of physostigmine through excised human skin from IPA:IPM mixtures was seen from the mixture exhibiting the highest solvation effect, giving additional evidence that physostigmine penetrates through the skin, possibly in combination with IPA.

Original languageEnglish
Pages (from-to)567-572
Number of pages6
JournalJournal of Pharmaceutical Sciences
Volume80
Issue number6
DOIs
StatePublished - Jun 1991

Funding

FundersFunder number
Tel Aviv University

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