DAPSONE

Prepared by Group 5:

Rudraksh JoshiKhushbu JethwaSonali KadamShirish Kadam

INTRODUCTION In the early 20th century, it is invented by the

German chemist Paul Ehrlich while working on selective toxicity .

Dapsone (diamino-diphenyl sulfone) is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy (MDT) for the treatment of Mycobacterium leprae infections (leprosy). Official in IP,BP,USP.

STRUCTURE4,4’-diaminodiphenylsulfone

SAR:::: Substitution of aromatic ring

with acetyl group results in decreased activity, increased solubility in water and decreased G.I irritation.

Replacement of 1 amino group with nitro,hydroxy or hydroxylamine results in decreased activity.

Replacement of both amino groups gives inactive product(with above).

SAR:::: Replacement of both amino

groups with aldehyde results in prodrug formation(eg.glucosulfone sodium).

Replacement of one of benzene rings with thiazole resulted in decreased activity.

SYNTHESIS

4,4’-dinitrodiphenyl sulfide

4,4’-diaminodiphenyl sulfone 4,4’-dinitrodiphenyl sulfone

2 + Na2S4,4’-dinitrodiphenyl sulfide 1-chloro-4-nitrobenzene Sodium sulfide

R.T

MECHANISM OF ACTION

1. Absorption It is completely absorbed after oral

administration

PHARMACOKINETICS

2. Distribution Approximately 70% bound to plasma

protein. The main metabolite, monoacetyl dapsone, is nearly 100% protein bound.

4 . EliminationThe plasma t1/2 is variable, though often>24hrsElimination takes 1-2 weeks or longerMetabolites are excreted in bile & urine

3.MetabolismDapsone is acetylated in the liver, the degree of which is genetically determined.

PHARMACOKINETICS

Mild haemolytic anaemia Gastric intolerance-nausea & anorexiamethaemoglobinaemia, headache,

paresthesias, mental symptoms & drug fever

allergic rashes, fixed drug eruption, hypermelanosis, phototoxicity& rarely exfoliative dermatitis

Hepatitis & agranulocytosisDapsone reaction/sulfone syndrome

ADVERSE ACTION

Hypersensitivity more frequent in patients receiving

multiple-drug therapy.The reaction involves a rash and may

also include fever, jaundice, and eosinophilia.

In general, these symptoms will occur within the first six weeks of therapy or not at all, and may be treated by corticosteroid therapy.

Dapsone reaction

Mycobacterium leprae infections (leprosy)./hansen’s disease

Acne.

Pneumocystis pneumonia.

Dermatitis Herpetiformis.

Toxoplasmosis - Prophylaxis

USES

DOSE DISEASE ADULT CHILDREN DAYS

Leprosy - Lepromatous

50-100 mg/day

6-10 mg/day 2-5 years

Leprosy - Tuberculoid

100 mg/day

NA 6 months

Dermatitis Herpetiformis

50-300 mg/day

NA Life long basis

Pneumocystis Pneumonia

100 mg/day

2 mg/kg/day 14-21 days

Pneumocystis Pneumonia Prophylaxis

100 mg/day

2 mg/kg/day Life long basis

Toxoplasmosis - Prophylaxis

100 mg/day

2 mg/kg/day Life long basis

Administered transdermally As a gel 5% topical acne medication available in 3-, 30-, and 60-gram tubes. In normal use, 0.5 grams should be

administered to the face per application twice a day.

TRANSDERMAL DOSE

PHYSICOCHEMICAL PROPERTIESMolecular Formula (C6H4NH2) 2SO2

Molecular weight 248.30 g/mol

Synonyms 4,4-Sulfonyldianiline; 4,4'-Sulfonylbisbenzenamine; 4-Aminophenyl sulfone; Sulfonyldianiline.

Physical state white crystalline powder.

Melting point 175 - 180 deg C

Odor NA 

Specific gravity NA 

Solubility insoluble in water , soluble in alcohol.

Vapors density 8.3 mg/ml

Stability Stable under ordinary conditions.

Before using this medication, consult with your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: folic acid antagonists (such as pyrimethamine), nitrofurantoin, primaquine.

This medication may decrease the effectiveness of combination-type birth control pills.

This can result in pregnancy.

DRUG INTERACTIONS:

A reversed-phase high performance liquid chromatography method is developed to simultaneously estimate serum concentrations of dapsone (DDS)

Mobile phase-mixture of n-heptane , ethyl acetate ,methanol,strong ammonia solution

Stationary phase-silica gel

Spectrophotometric determination of dapsone is also described

PH-6.98 λmax=525nm

ANALYTICAL METHOD

ANALYTICAL METHOD

Thin layer chromatography Mobile phase-mixture of n-heptane , ethyl acetate ,methanol,strong ammonia solution.Stationary phase-silica gel

The need for a more reliable route of administration led to investigation the possibility of an I.M. dapsone depot injection.

To achieve effective blood levels for 3-4 weeks, suspensions of large dapsone particles in an aqueous vehicle were made.

Studies in the rat revealed that dapsone-dependent methaemoglobinaemia could be greatly diminished by the co-administration of metabolic inhibitors(eg-cimetidine).

RECENT DEVELOPMENT

The need for a more reliable route of administration led to investigation the possibility of an I.M. dapsone depot injection.

To achieve effective blood levels for 3-4 weeks, suspensions of large dapsone particles in an aqueous vehicle were made.

Studies in the rat revealed that dapsone-dependent methaemoglobinaemia could be greatly diminished by the co-administration of metabolic inhibitors(eg-cimetidine).

RECENT DEVELOPMENT

STRENGTH VOLUME PRESENTATION

PRICE( Rs.)

Aczone Gel 5%w/w

30g Aczone Gel 46.00

MARKETED PRODUCTS

STRENGTH VOLUME PRESENTATION

PRICE( Rs.)

Dapsone 25mg 1000 DapsoneTAB(IP)

27.98

Dapsone 50mg 1000 DapsoneTAB(IP)

40.85

Dapsone 100mg 1000 DapsoneTAB(IP)

70.69

REFRENCES Williams D.et al ,Foye's principles of medicinal chemistry,

fifth edition, Lippincott's Williams & Wilkins John H.et al ,Wilson & Gisvolds textbook of organic medical

& pharmaceutical chemistry , eleventh edition ,Lippincott's Williams & Wilkins

Indian Pharmacopoeia, 2010,Volume I, 1162-1163 United states Pharmacopoeia,2009,Volume II, 2059-2060 Moncrief J. Journal of Chromatography B: Biomedical

Sciences and ApplicationsVolume 654, Issue 1, 18 March 1994, 103:110.

http://www.rxlist.com http:// www.medicinenet.com http://www.leprosy-information.org http://onlinelibrary.wiley.com