Die Pharmazie is published by IMR Press from Volume 81 Issue 1 (2026). Previous articles were published by another publisher under the CC-BY licence, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement.
Inclusion complexation of diazepam with different cyclodextrins in formulations for parenteral use
C. Holvoet 1, Y. Vander Heyden 2, J. Plaizier-Vercammen 3
Affiliations
Article Info
1 Department of Pharmaceutical Technology and Physical Pharmacy, Vrije Universiteit Brussel-VUB Brussels, Brussels, Belgium
2 Department of Pharmaceutical and Biomedical Analysis, Vrije Universiteit Brussel-VUB Brussels, Brussels, Belgium
3 Department of Pharmaceutical Technology and Physical Pharmacy, Vrije Universiteit Brussel-VUB Brussels, Laarbeeklaan 103, Brussels, 1090, Belgium, Email: jplaizie@vub.ac.be
Abstract
A parenteral formulation for the water-insoluble benzodiazepine diazepam was developed. Different cyclodextrins (CDs) suitable for parenteral injection: hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxypropyl-γ-cyclodextrin (HP-γ-CD), sulfobutylether-7-β-cyclodextrin (SBE-7-β-CD) and maltosyl-β-cyclodextrin (malt-β-CD) were used as alternatives to cosolvents to increase solubility. The increase in solubility displayed a concentration dependency for the four CDs used. Diazepam's solubility is enhanced linearly as a function of each CD concentration. The highest improvements in solubility (dissolved concentration circa 3.5 mg/ml in 40% CD) were found by adding HP-β-CD or SBE-7-β-CD. The additional use of polyvinylpyrrolidone (PVP) did not further increase the solubility of diazepam with HP-β-CD. A parenteral aqueous diazepam solution was prepared containing 10 mg diazepam/5 ml 30% HP-β-CD or SBE-7-β-CD solution. The preparations are in agreement with the requirements for parenteralia. Sterilisation by filtration is required since autoclaving degrades the active compound. The stability of the preparations, with and without pH adjustment to pH 5, was investigated during 18 months and during this period no noticeable degradation was observed.