Table 2. Summary details of some human clinical trials conducted on chitosan-based intranasal formulations.
| A. Studies conducted on drug-free solution or powder formulations of chitosan | ||||||||
|---|---|---|---|---|---|---|---|---|
| Study title [publication details] | CSN form | CSN conc. | CSN dose | Dosing regimen | No. subjects |
No. doses |
Conclusions on local adverse events | |
| #H1 | Tolerability of intranasal administration of a new excipient, chitosan glutamate [Archimedes, unpublished data] |
Solution Powder |
5mg/mL 100% |
4.0mg/day for 10 d 40mg/day for 10 d |
Multiple doses (0.1mL to both nostrils four times on Days 1–10) Multiple doses(10mg to both nostrils two times on Days 1–10) |
8 9 |
320 180 |
Safety was satisfactory and tolerability acceptable. |
| #H2 | Deposition, clearance and tolerability of chitosan solution [Newman et al. 2004] |
Solution | 5mg/mL | 0.5mg/day for 5 d | Multiple doses (0.1mL to one nostril on Days 1–5) Radiolabelled on Days 1, 3, 5 |
14 | 70 | Chitosan was well tolerated nasally |
| #H3 | In vivo mucociliary transport study using human volunteers [Aspden, et al. 1997] |
Solution | Approx. 6mg/mL† | ~0.6mg/day for 7 d |
Multiple doses (0.1mL to one nostril on Days 1–7) | 10 | 70 | Chitosan was well tolerated nasally and the nasal membrane appeared healthy and normal in all volunteers following endoscopic examination |
| B. Studies conducted on solution formulations of chitosan containing a drug | ||||||||
| #H4 | Pharmacokinetic profile of alniditan nasal spray during and outside migraine attacks [Roon, et al. 1999] |
Solution containing 20mg/mL alniditan | Not reported | Not reported | Two doses (0.1mL to one nostril on each of two days) | 13 | 53 | Intranasal alniditan administration was generally well tolerated. |
| Solution containing 40mg/mL alniditan | Not reported | Two doses (0.1mL to one nostril on each of two days) | 14 | |||||
| #H5 | Analgesic efficacy and safety of morphine-chitosan nasal solution in patients with moderate to severe pain following orthopedic surgery [Stoker et al. 2008] |
Solution containing 75mg/mL morphine | Not reported | Not reported | Single dose (0.05mL to one nostril) | 24 | 24 | Local adverse events associated with intranasal administration were transient and mainly of mild severity |
| Not reported | Single dose (0.1mL to one nostril) | 24 | 24 | |||||
| Not reported | Single dose (2 x 0.1mL) | 24 | 24 | |||||
| Not reported | Single dose (4 x 0.1mL) | 23 | 23 | |||||
| Not reported | Multiple doses (0.1mL to one nostril per dose)‡ | 90‡ | >90 | |||||
| Not reported | Multiple doses (2 x 0.1mL per dose) ‡ |
>87 | ||||||
| #H6 | The analgesic efficacy and safety of a novel intranasal morphine formulation (morphine plus chitosan), immediate release oral morphine, intravenous morphine, and placebo in a postsurgical dental pain model [Christensen et al. 2008] |
Solution#1 containing 75 mg/mL morphine |
Not reported | Not reported | Single dose (0.1mL to one nostril) | 45 | 45 | Study medications were generally well tolerated. |
| Solution#2 containing150 mg/mL morphine | 5mg/mL | Not reported | Single dose (0.1mL to one nostril) | 45 | 45 | |||
Note: †reported as 0.25% w/v as chitosan base; salt content = 42% w/w. ‡177 subjects received multiple doses of morphine-chitosan as follows: 7.5mg morphine (n = 90) or 15mg morphine (n = 87). Of these 177 subjects, 87 had already received single intranasal doses whereas the remaining 90 subjects received intranasal morphine-chitosan for the first time. CSN, chitosan glutamate.