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Acedapsone
The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Ashwini Nangia – One of the best experts on this subject based on the ideXlab platform.
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Pentamorphs of Acedapsone
Crystal Growth & Design, 2014Co-Authors: Geetha Bolla, Sudhir Mittapalli, Ashwini NangiaAbstract:Acedapsone is a long acting prodrug of Dapsone, the diacetyl derivative of diaminophenyl sulfone. It exhibits superior bioavailability compared to the parent drug. Dapsone occupies a preeminent position in the treatment of leprosy since the 1940s. Surprisingly no X-ray crystal structure or polymorphs of Acedapsone are reported. Five novel polymorphs of Acedapsone are reported (I–V) of which crystal forms I and II are characterized by single X-ray diffraction. These novel polymorphs were crystallized from solution, slow cooling of the melt, and spray-drying of the powder. Solution crystallization afforded Acedapsone Forms I and II. Slow cooling of the melt phase resulted in an amorphous phase, which transformed to a new Form IV slowly at room temperature, and then to Form III. Fast cooling or quick quench of the amorphous solid gave Form I. Spray drying resulted in a new metastable polymorph V, but this polymorph also converted to Form III at room temperature after 6 h. In addition to five crystalline poly…
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Pentamorphs of Acedapsone
, 2014Co-Authors: Geetha Bolla, Sudhir Mittapalli, Ashwini NangiaAbstract:Acedapsone is a long acting prodrug
of Dapsone, the diacetyl derivative
of diaminophenyl sulfone. It exhibits superior bioavailability compared
to the parent drug. Dapsone occupies a preeminent position in the
treatment of leprosy since the 1940s. Surprisingly no X-ray crystal
structure or polymorphs of Acedapsone are reported. Five novel polymorphs
of Acedapsone are reported (I–V) of which crystal forms I and
II are characterized by single X-ray diffraction. These novel polymorphs
were crystallized from solution, slow cooling of the melt, and spray-drying
of the powder. Solution crystallization afforded Acedapsone Forms
I and II. Slow cooling of the melt phase resulted in an amorphous
phase, which transformed to a new Form IV slowly at room temperature,
and then to Form III. Fast cooling or quick quench of the amorphous
solid gave Form I. Spray drying resulted in a new metastable polymorph
V, but this polymorph also converted to Form III at room temperature
after 6 h. In addition to five crystalline polymorphs of Acedapsone,
an amorphous phase was also obtained from the melt. XPac analysis
of polymorphs I and II (space group P21/n and C2/c) showed
2D isostructurality, and Hirshfeld surface analysis revealed subtle
differences in the molecular environment of the two crystal structures.
The stability of five polymorphs by DSC, VT-PXRD, and upon heating
in a sealed tube suggested that the kinetic stability order is Form
I (most stable) > II > III > IV > V > amorphous (least
stable), whereas
competitive slurry and liquid-assisted grinding experiments gave the
thermodynamic stability as Form II (most stable) > I > III >
IV >
V > amorphous (least stable). Solventless methods such as quench
cooling
of the melt and holding in a sealed tube at high temperature and pressure
yielded the kinetically stable Form I. Spray drying of the powder
gave metastable Forms III and V (which transformed over time), and
slurry conditions gave the thermodynamic Form II. The pentamorphic
system follows Ostwald’s law of stages. The role of solvent
selection in the direct crystallization of Acedapsone polymorphs after
diacetylation of Dapsone is also discussed
Joseph George – One of the best experts on this subject based on the ideXlab platform.
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Metabolism and interactions of antileprosy drugs.
Biochemical pharmacology, 2020Co-Authors: Joseph GeorgeAbstract:Abstract Leprosy is a chronic infectious disease caused my Mycobacterium leprae that primarily affects peripheral nervous system and extremities and is prevalent in tropical countries. Treatment for leprosy with multidrug regimens is very effective compared to monotherapy especially in multibacillary cases. The three major antileprosy drugs currently in use are 4, 4′-diaminodiphenyl sulfone (DDS, dapsone), rifampicin, and clofazimine. During multidrug therapy, the potent antibiotic rifampicin induces the metabolism of dapsone, which results in decreased plasma half-life of dapsone and its metabolites. Furthermore, rifampicin induces its own metabolism and decreases its half-life during monotherapy. Rifampicin upregulates several hepatic microsomal drug-metabolizing enzymes, especially cytochrome P450 (CYP) family that in turn induce the metabolism of dapsone. Clofazimine lacks significant induction of any drug-metabolizing enzyme including CYP family and does not interact with dapsone metabolism. Rifampicin does not induce clofazimine metabolism during combination treatment. Administration of dapsone in the acetylated form (Acedapsone) can release the drug slowly into circulation up to 75 days and could be useful for the effective treatment of paucibacillary cases along with rifampicin. This review summarizes the major aspects of antileprosy drug metabolism and drug interactions and the role of cytochrome P450 family of drug metabolizing enzymes, especially CYP3A4 during multidrug regimens for the treatment of leprosy.
Geetha Bolla – One of the best experts on this subject based on the ideXlab platform.
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Pentamorphs of Acedapsone
Crystal Growth & Design, 2014Co-Authors: Geetha Bolla, Sudhir Mittapalli, Ashwini NangiaAbstract:Acedapsone is a long acting prodrug of Dapsone, the diacetyl derivative of diaminophenyl sulfone. It exhibits superior bioavailability compared to the parent drug. Dapsone occupies a preeminent position in the treatment of leprosy since the 1940s. Surprisingly no X-ray crystal structure or polymorphs of Acedapsone are reported. Five novel polymorphs of Acedapsone are reported (I–V) of which crystal forms I and II are characterized by single X-ray diffraction. These novel polymorphs were crystallized from solution, slow cooling of the melt, and spray-drying of the powder. Solution crystallization afforded Acedapsone Forms I and II. Slow cooling of the melt phase resulted in an amorphous phase, which transformed to a new Form IV slowly at room temperature, and then to Form III. Fast cooling or quick quench of the amorphous solid gave Form I. Spray drying resulted in a new metastable polymorph V, but this polymorph also converted to Form III at room temperature after 6 h. In addition to five crystalline poly…
-
Pentamorphs of Acedapsone
, 2014Co-Authors: Geetha Bolla, Sudhir Mittapalli, Ashwini NangiaAbstract:Acedapsone is a long acting prodrug
of Dapsone, the diacetyl derivative
of diaminophenyl sulfone. It exhibits superior bioavailability compared
to the parent drug. Dapsone occupies a preeminent position in the
treatment of leprosy since the 1940s. Surprisingly no X-ray crystal
structure or polymorphs of Acedapsone are reported. Five novel polymorphs
of Acedapsone are reported (I–V) of which crystal forms I and
II are characterized by single X-ray diffraction. These novel polymorphs
were crystallized from solution, slow cooling of the melt, and spray-drying
of the powder. Solution crystallization afforded Acedapsone Forms
I and II. Slow cooling of the melt phase resulted in an amorphous
phase, which transformed to a new Form IV slowly at room temperature,
and then to Form III. Fast cooling or quick quench of the amorphous
solid gave Form I. Spray drying resulted in a new metastable polymorph
V, but this polymorph also converted to Form III at room temperature
after 6 h. In addition to five crystalline polymorphs of Acedapsone,
an amorphous phase was also obtained from the melt. XPac analysis
of polymorphs I and II (space group P21/n and C2/c) showed
2D isostructurality, and Hirshfeld surface analysis revealed subtle
differences in the molecular environment of the two crystal structures.
The stability of five polymorphs by DSC, VT-PXRD, and upon heating
in a sealed tube suggested that the kinetic stability order is Form
I (most stable) > II > III > IV > V > amorphous (least
stable), whereas
competitive slurry and liquid-assisted grinding experiments gave the
thermodynamic stability as Form II (most stable) > I > III >
IV >
V > amorphous (least stable). Solventless methods such as quench
cooling
of the melt and holding in a sealed tube at high temperature and pressure
yielded the kinetically stable Form I. Spray drying of the powder
gave metastable Forms III and V (which transformed over time), and
slurry conditions gave the thermodynamic Form II. The pentamorphic
system follows Ostwald’s law of stages. The role of solvent
selection in the direct crystallization of Acedapsone polymorphs after
diacetylation of Dapsone is also discussed