Registration Dossier

Physical & Chemical properties

Endpoint summary

Administrative data

Description of key information

Additional information

Appearance/physical state/coloue:

White, odorless, crystalline solid that is essentially non-hygroscopic.

Partition coefficient:

LogKow of the test substance in the key study (Wyeth, 1991) is >0.4 -<600. Based on the ionization potential of the compound, the log PCapp increased as pH.

Water solubility:

The key study (Wyeth, 1991) shows that solutilities within the physiological pH range were 540, 542, 501 and 21.6 mg/mL at pH 1.0, 5.38, 7.09, 7.97, respectively, and the test substance is very souble in water.

Explosiveness:

Two studies are available. The studies (Chilworth Technology Ltd, 1997 and Chilworth Technology, Inc, 2004) show that the test substance is explosive under influence of flame.

Storage stability and reactivity towards container material:

The study (Wyeth, 1991) was divided into pyrex container and amder glass ampules.

In pyrex vessels, the only degradation product detected at pH 1 was 1-[2-(dimethylamino)-1-(4-methoxyphenyl) ethyl] cyclohexene.

In the amber glass ampules, a total of eight degradation products were detected - seven of which were identified. At low pH (1-4), the major degradation product was 1-[2-(dimethylamino)-1-(4-methoxyphenyl) ethyl] cyclohexene. At high pH (8-10), the major degradation product was 1-[1-(4-methoxyphenyl)-2-(methylamino)ethyl]cyclohexanol. From pH 5-7, the major degradation product observed was 3-methoxybenzaldehyde. However, the reaction rate was extremely slow in the pH range of 5-7.

Stability: thermal, sunlight, metals:

The study (Wyeth, 1991) fell into thermal reaction in solid state, Fluorescent Photodegradation in solid state and UV Photodegradation in solid state.

When the test substance was stored at 120℃ for 20 weeks, approximately 15% degradation occurred.

Solid state degradation studies of the test substance showed that it to be stable under 500 foot-candles of fluorescent light at 25℃. When the test substance was exposed to 35 watts of UV light centered at 254 nm, a loss in potency of approximately 15% after 11 days was observed.

Dissociation constant:

By potentiometric titration, the pKa was found to be 9.4.

Additional physico-chemical information:

The study (Wyeth, 1991) fell into hygroscopicity, intrinsic dissolution rate and polymorphic crystal form comparison.

At room temperature (23℃), the test substance is essentially non-hygroscopic.

The intrinsic dissolution rate was found to be essentially unaffected by pH in the pH range of 1-8 and was found to be approximately 3.5E-04 g/cm2-sec. The results suggest that no dissolution rate-limiting absorption should occur.

The test substance was found to exist in at least three polymorphic forms. Form I and Form II have been producted from synthetic procedures. From III has only been formed by sulimation of Form I at high temperatures under atmospheric pressure. At 150℃, Form II is more stable than Form I and is the acceptable form for all development and production purposes. Form I and Form II are equal in terms of aqueous solubility, intrinsic dissolution rate and hygroscopicity.