Dapsone

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test:
If mean concentration of the substance remains >90% after 91 days storage, the substance is considered stable.
- Short description of test conditions:
Commercially available dapsone tablets (25 mg) were used to prepare the suspensions: the first in simple syrup and water with citric acid, the second in 1:1 Ora Sweet:Ora Plus to yield a concentration of 2.0 mg/mL. The dosage forms were stored in 10 amber plastic prescription bottles. Five were stored at 25 degrees C and five at 4 degrees C. Three samples were taken from each of five bottles at 0, 7, 14, 28, 42, 56, 70, and 91 days (n = 15). Dapsone concentrations in each sample were measured in duplicate by a validated and stability-indicating HPLC method; the pH of each sample was also determined. The drug was considered stable if the mean concentration > or =90% of the original concentration.

- Parameters analysed / observed:
Concentration of dapsone in samples after 0-91 days storage, analyzed using HPLC.

Ora-Sweet contains purified water, sucrose, glycerin, sorbitol (5%), flavoring, sodium phosphate, and citric acid as buffering agents and potassium sorbate and methylparaben as preservatives. It is buffered to a pH of approximately 4.2 and has an osmolality of about 3,240 mOsm/kg.

GLP compliance:

not specified

Specific details on test material used for the study:

Dapsone (16 tablets, 25 mg each)a was used to prepare the suspensions. The tablets were ground to powder using a mortar and pestle, and then two suspensions were prepared. The first suspension was made in 1:1 Ora Sweetb:Ora Plusc while mixing; the second was prepared in citric acid (1 g dissolved in 50 mL distilled water) and 150 mL of simple syrup NFf while mixing. The concentration of dapsone in each suspension was 2.0 mg/mL. Both dapsone suspensions were stored in 10 amber plastic prescription bottles (2 oz each).

Ora-Sweet contains purified water, sucrose, glycerin, sorbitol (5%), flavoring, sodium phosphate, and citric acid as buffering agents and potassium sorbate and methylparaben as preservatives. It is buffered to a pH of approximately 4.2 and has an osmolality of about 3,240 mOsm/kg.

Analytical monitoring:

not specified

Transformation products:

not measured

Details on hydrolysis and appearance of transformation product(s):

Dapsone does not hydrolyse

% Recovery:

> 95

Temp.:

25 °C

Duration:

91 d

% Recovery:

> 95

Temp.:

4 °C

Duration:

91 d

Remarks on result:

other: Hydrolytically stable based on published information

Validity criteria fulfilled:

not specified

Conclusions:

Dapsone was stable for at least three months at 4 degrees C and 25 degrees C

Executive summary:

Dapsone tablets (25 mg) were used to prepare the suspensions: the first in simple syrup and water with citric acid, the second in 1:1 Ora Sweet:Ora Plus to yield a concentration of 2.0 mg/mL. The dosage forms were stored in 10 amber plastic prescription bottles. Five were stored at 25 degrees C and five at 4 degrees C. Three samples were taken from each of five bottles at 0, 7, 14, 28, 42, 56, 70, and 91 days (n = 15). Dapsone concentrations in each sample were measured in duplicate by a validated and stability-indicating HPLC method; the pH of each sample was also determined. The mean concentrations of dapsone were >95% of the initial concentrations for 91 days at both 4 degrees C and 25 degrees C in each suspension. There was a slight darkening of the samples stored at 25 degrees C. Dapsone was stable in two suspensions prepared from commercially available tablets for at least three months at 4 degrees C and 25 degrees C.

Description of key information

The substance does not contain a hydrolysable bond therefore no hydrolysis is possible. The stability of dapsone has been demonstrated using commercially available dapsone tablets.