This study has shown that it is possible to
enhance cyclodextrin solubilization of benzodiazepines
through reversible ring-opening of the
benzodiazepine ring and ionization. Additional
solubilization was obtained through interaction of
a water-soluble polymer with the drug:cyclodextrin
complex. Through this multiple techniques it
was possible to minimize the amount of cyclodextrin
needed to solubilize the benzodiazepine drug
in the aqueous nasal spray solution, keeping the
drug:cyclodextrin ratio close to one. A physiologically
acceptable aqueous nasal spray solution
containing 17 mg of midazolam per 1 ml at pH
4.3 was tested in humans. After i.n. administration
of this formulation, midazolam was rapidly
absorbed from the nasal cavity into the systemic
circulation without causing notable nasal