Why Sulphonamide Are Sparingly Soluble In Water

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activity seems to be exhibited by sulfonamides between pKa 6.6 and 7.4.123-126 This reflects, in part, the need for enough nonionized (i.e., more lipid soluble) drug to be present at physiological pH to be able to pass through bacterial cell walls.127 Fujita and Hansch113 also related pKa, partition coefficients, and electronic (Hammett) parameters with sulfonamide activity (Table 6.9).


4-Amino-N-(5-methyl-1,3,4-thiadiazole-2yl)benzenesulfon-amide; N1-(5-methyl-1,3,4-thiadiazol-2-yl)sulfanilamide; 5-methyl-2-sulfanilamido-1,3,4-thiadiazole. Sulfamethizole's plasma half-life is 2.5 hours. This compound is a white crystalline powder soluble 1:2,000 in water.


4-Amino-N-(3,4-dimethyl-5-isoxazolyl)benzenesulfon-amide; J^1-(3,4-dimethyl-5-isoxazolyl) sulfanilamide; 5-sul-fanilamido-3,4-dimethylisoxazole. Sulfisoxazole's plasma half-life is 6 hours. This compound is a white, odorless, slightly bitter, crystalline powder. Its pKa is 5.0. At pH 6, this sulfonamide has a water solubility of 350 mg in 100 mL, and its acetyl derivative has a solubility of 110 mg in 100 mL of water.

Dimethylacetamide Pka

Sulfisoxazole possesses the action and the uses of other sulfonamides and is used for infections involving sulfon-amide-sensitive bacteria. It is claimed to be effective in the treatment of Gram-negative urinary infections.

Sulfisoxazole Acetyl

N-[(4-Aminophenyl)sulfonyl]-N-(3,4-dimethyl-5-isoxa-zolyl)acetamide; N-(3,4-dimethyl-5-isoxazolyl)-N-sulfanily-

lacetamide; ^1-acetyl-^1-(3,4-dimethyl-5-isoxazolyl)sul-fanilamide. Sulfisoxazole acetyl shares the actions and uses of the parent compound, sulfisoxazole. The acetyl derivative is tasteless and, therefore, suitable for oral administration, especially in liquid preparations. The acetyl compound is split in the intestinal tract and absorbed as sulfisoxazole; that is, it is a prodrug for sulfisoxazole.

Sulfisoxazole Diolamine

4-Amino-N-(3,5-dimethyl-5-isoxazolyl)benzenesulfon-amide compound with 2,2'-iminobis[ethanol](1:1); 2,2'-iminodiethanol salt of ^-(3,4-dimethyl-5-isoxazolyl)sul-fanilamide. This salt is prepared by adding enough diethanolamine to a solution of sulfisoxazole to bring the pH to about 7.5. It is used as a salt to make the drug more soluble in the physiological pH range of 6.0 to 7.5 and is used in solution for systemic administration of the drug by slow intravenous, intramuscular, or subcutaneous injection when high enough blood levels cannot be maintained by oral administration alone. It also is used for instillation of drops or ointment in the eye for the local treatment of susceptible infections.


4-Amino-N -(4,6-dimethyl-2-pyrimidinyl)benzenesul-fonamide; ^1-(4,6-dimethyl-2-pyrimidinyl)sulfanilamide; 2-sulfanilamido-4,6-dimethylpyrimidine. Sulfamethazine's plasma half-life is 7 hours. This compound is similar in chemical properties to sulfamerazine and sulfadiazine but does have greater water solubility than either. Its pKa is 7.2. Because it is more soluble in acid urine than sulfamerazine is, the possibility of kidney damage from use of the drug is decreased. The human body appears to handle the drug unpredictably; hence, there is some disfavor to its use in this country except in combination sulfa therapy (in trisul-fapyrimidines, USP) and in veterinary medicine.


N-[(4-Aminophenyl)sulfonyl]-acetamide; N-sulfanilylac-etamide; N1-acetylsulfanilamide. Sulfacetamide's plasma half-life is 7 hours. This compound is a white crystalline powder, soluble in water (1:62.5 at 37°C) and in alcohol. It is very soluble in hot water, and its water solution is acidic. It has a pKa of 5.4.


^1-(6-Chloro-3-pyridazinyl) sulfanilamide. Sulfachloro-pyridazine's plasma half-life is 8 hours.


4-Amino-N-2-pyridinylbenzenesulfonamide; ^-2-pyridyl-sulfanilamide. Sulfapyridine's plasma half-life is 9 hours. This compound is a white, crystalline, odorless, and tasteless substance. It is stable in air but slowly darkens on exposure to light. It is soluble in water (1:3,500), in alcohol (1:440), and in acetone (1:65) at 25°C. It is freely soluble in dilute mineral acids and aqueous solutions of sodium and potassium hydroxide. The pKa is 8.4. Its outstanding effect in curing pneumonia was first recognized by Whitby; however, because of its relatively high toxicity, it has been supplanted largely by sulfadiazine and sulfamerazine. Several cases of kidney damage have resulted from acetylsulfapyri-dine crystals deposited in the kidneys. It also causes severe nausea in most patients. Because of its toxicity, it is used only for dermatitis herpetiformis.

Sulfapyridine was the first drug to have an outstanding curative action on pneumonia. It gave impetus to the study of the whole class of N1 heterocyclically substituted derivatives of sulfanilamide.


4-Amino-N-(5-methyl-3-isoxazolyl)benzenesulfonamide; ^1-(5-methyl-3-isoxazolyl) sulfanilamide (Gantanol). Sulfamethoxazole's plasma half-life is 11 hours.

Sulfamethoxazole is a sulfonamide drug closely related to sulfisoxazole in chemical structure and antimicrobial activity. It occurs as a tasteless, odorless, almost white crystalline powder. The solubility of sulfamethoxazole in the pH range of 5.5 to 7.4 is slightly lower than that of sulfisoxazole but higher than that of sulfadiazine, sulfamerazine, or sul-famethazine.

Following oral administration, sulfamethoxazole is not absorbed as completely or as rapidly as sulfisoxazole, and its peak blood level is only about 50% as high.


4-Amino-N-2-pyrimidinyl-benzenesulfonamide; N1-2-pyrimidinylsulfanilamide; 2-sulfanilamidopyrimidine. Sulfadiazine's plasma half-life is 17 hours. It is a white, odorless crystalline powder soluble in water to the extent of 1:8,100 at 37°C and 1:13,000 at 25°C, in human serum to the extent of 1:620 at 37°C, and sparingly soluble in alcohol and acetone. It is readily soluble in dilute mineral acids and bases. Its pKa is 6.3.

Sulfadiazine Sodium

Soluble sulfadiazine is an anhydrous, white, colorless, crystalline powder soluble in water (1:2) and slightly soluble in alcohol. Its water solutions are alkaline (pH 9-10) and absorb carbon dioxide from the air, with precipitation of sulfa-diazine. It is administered as a 5% solution in sterile water intravenously for patients requiring an immediately high blood level of the sulfonamide.

Mixed Sulfonamides

The danger of crystal formation in the kidneys from administration of sulfonamides has been greatly reduced through the use of the more soluble sulfonamides, such as sulfisoxazole. This danger may be diminished still further by administering mixtures of sulfonamides. When several sulfonamides are administered together, the antibacterial action of the mixture is the summation of the activity of the total sulfonamide concentration present, but the solubilities are independent of the presence of similar compounds. Thus, by giving a mixture of sulfadiazine, sulfamerazine, and sulfacetamide, the same therapeutic level can be maintained with much less danger of crystalluria, because only one third of the amount of any one compound is present. Descriptions of some of the mixtures used follow.

Trisulfapyrimidines, Oral Suspension

The oral suspension of trisulfapyrimidines contains equal weights of sulfadiazine, USP; sulfamerazine, usp; and sulfamethazine, USP, either with or without an agent to raise the pH of the urine.

Trisulfapyrimidines, Tablets

Trisulfapyrimidine tablets contain essentially equal quantities of sulfadiazine, sulfamerazine, and sulfamethazine.

Sulfadoxine and Pyrimethamine

The mixture of sulfadoxine and pyrimethamine (Fansidar) is used for the treatment of P. falciparum malaria in patients in whom chloroquine resistance is suspected. It is also used for malaria prophylaxis for travelers to areas where chloro-quine-resistant malaria is endemic.

This compound is particularly effective against Clostridium welchii in topical application and was used during World War II by the German army for prophylaxis of wounds. It is not effective orally. It is currently used alone or with antibiotics in the treatment of slow-healing, infected wounds.

Topical Sulfonamides

Sulfacetamide Sodium

N-Sulfanilylacetamide monosodium salt (Sodium Sulamyd) is obtained as the monohydrate and is a white, odorless, bitter, crystalline powder that is very soluble (1:2.5) in water. Because the sodium salt is highly soluble at the physiological pH of 7.4, it is especially suited, as a solution, for repeated topical applications in the local management of ophthalmic infections susceptible to sulfonamide therapy.

Sulfisoxazole Diolamine

Sulfisoxazole diolamine is described with the short- and intermediate-acting sulfonamides and also used in intravenous and intramuscular preparations.


Some patients treated for burns with large quantities of this drug have developed metabolic acidosis. To overcome this adverse effect, a series of new organic salts was prepared.16 The acetate in an ointment base proved to be the most efficacious.

Silver Sulfadiazine (Silvadene)

The silver salt of sulfadiazine applied in a water-miscible cream base has proved to be an effective topical antimicrobial agent, especially against Pseudomonas spp. This is particularly significant in burn therapy because pseudomonads are often responsible for failures in therapy. The salt is only slightly soluble and does not penetrate the cell wall but acts on the external cell structure. Studies using radioactive silver have shown essentially no absorption into body fluids. Sulfadiazine levels in the serum were about 0.5 to 2 mg/100 mL.

Triple Sulfa

Triple sulfa (sulfabenzamide, sulfacetamide, and sulfathia-zole; Femguard) is used as a vaginal cream in the treatment of Haemophilus vaginalis vaginitis.

Nonabsorbable Sulfonamides


4-(Aminomethyl)benzenesulfonamide acetate (Sulfamylon) is a homologue of the sulfanilamide molecule. It is not a true sulfanilamide-type compound, as it is not inhibited by PABA. Its antibacterial action involves a mechanism that differs from that of true sulfanilamide-type compounds.

This preparation is reported to be easier to use than other standard burn treatments, such as application of freshly prepared dilute silver nitrate solutions or mafenide ointment.

Sulfonamides for Intestinal Infections, Ulcerative Colitis, or Reduction of Bowel Flora

Each of the sulfonamides in this group is a prodrug, which is designed to be poorly absorbable, though usually, in practice, a little is absorbed. Therefore, usual precautions with sulfonamide therapy should be observed. In the large intestine, the N4-protecting groups are cleaved, releasing the free sulfonamide antibacterial agent. Today, only one example is used clinically, sulfasalazine.


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  • karolin lowe
    Why sulphonamide are sparingly soluble in water?
    3 years ago
  • Ayla
    What is the salt of sulphonamide?
    2 years ago
  • justin
    Why is sulfanilamide insoluble in water?
    2 years ago
  • Juliane
    Why is sulfadiazine not soluble in water?
    2 years ago
  • Hilda
    Is sulfisoxazole the most soluble sulphonamide?
    1 year ago
  • Frances
    Are sulfonamides soluble in water?
    8 months ago

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