Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

6. Project II: Pharmacokinetic of transmucosal nasal delivered midazolam – impact of adjuvants
8
7
6
5
4
3
2
1
0
indifferent tolerable disagreeable painful
Preparation 1 0 7 1 0
Preparation 2 0 6 2 0
Preparation 3 0 7 1 0
Preparation 4 2 4 2 0
Preparation 5 2 2 4 0
Figure 6-3: Tolerability of nasal administration of Preparation 1 to 5 to 8 healthy volunteers.
Immediately after administration volunteers classified the nasal administration of Preparation 1 to 5 as
indifferent, tolerable, disagreeable, or painful.
Nasal administration of midazolam (Preparation 1 to 5) caused some irritation in the nose or throat
area immediately after administration (see Figure 6-4).
7
Frequency
6
5
4
3
2
Throat
Nose
1
0
P1 P2 P3 P4 P5 P1 P2 P3 P4 P5 P1 P2 P3 P4 P5 P1 P2 P3 P4 P5 P1 P2 P3 P4 P5
very slight slight intermediate strong very strong
Figure 6-4: Local irritation immediately after nasal administration of Preparation 1 to 5 (P1, P2, P3, P4,
and P5). Volunteers (n=8) rated the intensity immediately after nasal administration of the study
medication.
Changes of local irritation assessed immediately to 4 h after nasal administration of study
medication is shown Appendix 10.3.5. and 10.3.6.
Within 30 minutes after nasal administration (Preparation 1 to 5) nasal irritation was completely
reversible. Nasal irritation after administration of Preparation 1, 2, and 3 (nasal delivery of 1 mg
Katja Suter-Zimmermann Page 66 of 188 University of Basel, 2008