Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

5. Project I: Development of preparations for transmucosal nasal midazolam delivery
5.3 Results
5.3.1 Solubility studies
80
70
BR buffer
BR buffer + 10%RMbCD
BR buffer + 10%HPbCD
Figure 5-2 shows pH-dependent
solubility of midazolam in BR buffer
and in BR buffer with 10% RMβCD,
Midazolam consentration [mg/ml]
60
50
40
30
20
10
BR buffer + 10%HPgCD
10% HPβCD, and 10% HPγCD.
All tested cyclodextrin derivatives
enhance midazolam solubility, but not
independent of pH.
In Table 5-2 maximal midazolam
concentrations in BR buffer and
BR buffer with 10% RMβCD,
10% HPβCD, and 10% HPγCD are
listed.
0
2 3 4 5 6 7
pH
Figure 5-2: pH-dependent solubility of midazolam. In
BR buffer (40 mM boric acid, 40 mM acetic acid, 40 mM
phosphoric acid; pH, adjusted with 1.0 M sodium
hydrochloride) with and without solubilizer (10% RMβCD,
10% HPβCD, and 10% HPγCD).
Table 5-2: Midazolam solubilized with 10% RMβCD, 10% HPβCD, and 10% HPγCD.
pH
Midazolam hydrochloride solubility (mg/ml) in:
RB buffer (pH 3.5) + 10% RMβCD + 10% HPβCD + 10% HPγCD
3.0 56.4 68.1 70.3 68.0
3.5 3.4 --- --- ---
4.0 3.8 42.4 33.3 52.8
4.5 1.5 --- --- ---
5.0 0.5 10.0 4.4 2.6
7.4 --- 2.53 0.8 0.6
Katja Suter-Zimmermann Page 49 of 188 University of Basel, 2008