Chlorothiazide Sodium

Effect of chlorothiazide on serial measurements of exchangeable sodium and blood pressure in spontaneously hypertensive rats.[Pubmed:4053506]

Clin Sci (Lond). 1985 Nov;69(5):511-5.

Chlorothiazide (100 mg/kg body weight) was given by gavage daily to spontaneously hypertensive rats for 4 weeks. Another group of spontaneously hypertensive rats was given only tap water and served as control. Measurements of total exchangeable sodium, blood pressure and weight were performed for 2 weeks before and for 4 weeks during treatment. Before treatment, exchangeable sodium, blood pressure and weight were similar in the two groups of rats. Chlorothiazide significantly attenuated the blood pressure increase in spontaneously hypertensive rats, the effect being most marked during the first 2 1/2 weeks of treatment and less thereafter. Rats in the chlorothiazide-treated group gained weight more slowly than did those of the control group. Exchangeable sodium, expressed as mmol/kg body weight, did not differ significantly between the two groups at any stage. When exchangeable sodium was expressed as mmol/rat, there was a more gradual rise in the chlorothiazide-treated animals, in accordance with their slower gain in weight. There was no temporal association between the antihypertensive effect of chlorothiazide and changes in exchangeable sodium. Thus whereas chlorothiazide treatment of spontaneously hypertensive rats slows the increase of both weight and exchangeable sodium, other mechanisms are apparently responsible for the antihypertensive action of the drug.

Stability of chlorothiazide sodium in polypropylene syringes.[Pubmed:26195655]

Am J Health Syst Pharm. 2015 Aug 1;72(15):1292-7.

PURPOSE: The stability of a solution of chlorothiazide injection diluted with sterile water and stored in polypropylene syringes under refrigerated conditions was investigated. METHODS: Chlorothiazide solutions were compounded by adding 20 mL of sterile water for injection to a 500-mg vial of Chlorothiazide Sodium for injection. Six batches of chlorothiazide solution (25 mg/mL) were compounded; 0.5-mL portions were transferred to 1-mL polypropylene syringes, which were sealed with a Luer tip cap and stored at refrigeration temperatures (2-8 degrees C) protected from light. Three batches were potency tested by stability-indicating high-performance liquid chromatography (HPLC) assay using a 0.5-mL sample from each batch at designated time points. Visual and pH testing were performed using the three remaining batches; the contents of two syringes per batch were combined and visually inspected for container integrity and solution color and clarity, with duplicate pH testing performed at each time point. RESULTS: HPLC analyses showed that the remaining percentage of the initial chlorothiazide content declined at an average daily rate of 1.4%, decreasing to 93% by day 6. All samples remained intact, clear, and colorless, with no visible particulate matter or precipitation observed throughout the study period. For all samples of chlorothiazide solution, pH values remained within the range of 9.2-10.0 throughout the 10-day study period. CONCLUSION: When packaged in 1-mL polypropylene syringes and stored protected from light at refrigerated conditions, a solution of Chlorothiazide Sodium injection in water was stable for six days.

Preparation and solid state characterisation of chlorothiazide sodium intermolecular self-assembly suprastructure.[Pubmed:20816757]

Eur J Pharm Sci. 2010 Dec 23;41(5):603-11.

Chlorothiazide (CTZ), unlike other thiazide diuretics, can form salts. An injectable formulation containing the sodium salt is available; however neither the physicochemical characteristics of the salt nor its solid state form have been previously reported. This work reports on the crystal structure of Chlorothiazide Sodium. The structure was investigated by single crystal X-ray and nuclear magnetic spectroscopy (NMR) analyses and compared to chlorothiazide, while the solid state characteristics were assessed by thermal analysis, powder X-ray diffraction, infrared spectroscopy, dynamic moisture sorption and solubility analysis. The crystal structure of Chlorothiazide Sodium was determined to be triclinic; the crystal space group type was P-1. Chlorothiazide Sodium presented a self-assembly polymeric-type suprastucture, where the unit cell comprised two chlorothiazide molecules bonded together with sodium cations through the water bridges. The coordinate centre comprised the following: (CTZ)(3).(H(2)O).Na(H(2)O)(2)Na.(H(2)O).(CTZ)(3). The crystalline material was determined to be a monosodium dihydrate, stable in the range of 10-90% relative humidity (RH) at 25 degrees C. Additional processing of the salt resulted in a crystalline anhydrous form which was stable in the range 0-20% RH at 25 degrees C. The aqueous solubility of the Chlorothiazide Sodium dihydrate at 37 degrees C was found to be approximately 400-fold higher than that of chlorothiazide, which may present biopharmaceutical advantages for the salt compared to the non-salt form.