Timolol Maleate

Timolol is a beta blocker medication used either by mouth or as eye drops. Timolol Maleate is used to treat high pressure inside the eye due to glaucoma (open angle-type) or other eye diseases. Lowering high pressure inside the eye helps to prevent blindness.

General Properties and Specifications of Timolol Maleate as pe IP:
Appearance: A white or almost white crystals or powder.
Assay: 98.5% to 101% C13H24N4O3S-C4H4O4.
Identification: IR.
Appearance of the solution: a 2% solution in water is clear and not more intensely colored than the reference solution.
pH: 3.8 to 4.3 in 2% solution.
Specific optical rotation: -5.7 to -6.2
Enantiomeric purity: by HPLC: Impurity A: NMT 1.0%
Related substances:
Impurity B: NMT 0.1%
Impurity C: NMT 0.1%
Impurity D: NMT 0.1%
Impurity F: NMT 0.1%
Individual unspecified impurity: NMT 0.1%
Total Impurities: NMT 0.4%
Sulfated Ash: NMT 0.1%
Loss on drying at 105C for 3h: NMT 0.5%
Residual Solvent:
Acetone: NMT 1000 ppm.
Methylene Chloride: NMT 500 ppm.
tert-Butanol: NMT 500 ppm.
Benzene: NMT 2 ppm.
Melting Point: 198C literature.
Solubility: Soluble in water and methanol, ethanol (96%). Sparingly soluble in chloroform.
Storage: Room temperature. Preferably refrigerate.

Timolol Maleate USP Grade Specifications:
C13H24N4O3S-C4H4O4 --- 432.49
2-Propanol, 1-[(1,1-dimethylethyl)amino]-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-, (S)-, (Z)-2-butenedioate (1:1) (salt);
(−)-1-(tert-Butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy]-2-propanol maleate (1:1) (salt) CAS 26921-17-5
UNII: P8Y54F701R
UNII: 5JKY92S7BR

DEFINITION
Timolol Maleate contains NLT 98.0% and NMT 102.0% of timolol maleate (C13H24N4O3S-C4H4O4), calculated on the dried basis.

IDENTIFICATION
A. Infrared Absorption
B. Ultraviolet Absorption
C. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
Residue on Ignition: NMT 0.1%
Organic Impurities: To pass the test.
Optical Rotation, Specific Rotation:
Sample solution: 50 mg/mL of Timolol Maleate in 1.0 N hydrochloric acid.
Acceptance criteria: −11.7° to −12.5° (λ = 405 nm)
pH: For 20 mg/mL of Timolol Maleate in water. Acceptance criteria: 3.8–4.3
Loss on Drying: Dry under vacuum at 100C to constant weight. Acceptance criteria: NMT 0.5%

Timolol Maleate BP Ph Eur Grade:
C17H28N4O7S --- 432.5 CAS 26921-17-5

DEFINITION
(2S)-1-[(1,1-Dimethylethyl)amino]-3-[[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy]propan-2-ol (Z)-butenedioate.
Content: 98.5 per cent to 101.0 per cent (dried substance).

CHARACTERS
Appearance: White or almost white, crystalline powder or colourless crystals.
Solubility: Soluble in water and in ethanol (96 per cent).
mp: about 199C, with decomposition.

IDENTIFICATION
First identification: A, B
Second identification: A, C, D
A. Specific optical rotation: -6.2 to -5.7.
Dissolve 1.000 g in 1 M hydrochloric acid and dilute to 10.0 mL with the same acid.
B. Infrared absorption spectrophotometry.
C. Thin-layer chromatography.
D. To pass the test.

Solution S: Dissolve 0.5 g in carbon dioxide-free water and dilute to 25 mL with the same solvent.
Appearance of solution: Solution S is clear and not more intensely coloured than reference solution.
pH: 3.8 to 4.3 for solution S.
Enantiomeric purity: To pass the test. --- 1.0 per cent.
Related substances: To pass the test.
Loss on drying: Maximum 0.5 per cent, determined on 1.000& g by drying in an oven at 105C.
Sulfated ash: Maximum 0.1 per cent, determined on 1.0 g.
Storage: Protected from light.

For Original Monographs of IP Indian Pharmacopoeia EP Ph Eur European Pharmacopoeia BP British Pharmacopoeia USP US Pharmacopoeia FCC Food Grade product, please check with the respective web-pages or books.