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...
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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
Sudhir Mittapalli - 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
Cássia Baldini Soares - One of the best experts on this subject based on the ideXlab platform.
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Rifampicin chemoprophylaxis in preventing leprosy in contacts of patients with leprosy: a comprehensive systematic review protocol
JBI database of systematic reviews and implementation reports, 2015Co-Authors: Silvana Margarida Benevides Ferreira, Tatiana Yonekura, Juliana Takahashi, Eliane Ignotti, Denise Da Costa Boamorte Cortela, Cássia Baldini SoaresAbstract:Review question/objective 1. What is the effectiveness of rifampicin chemoprophylaxis in preventing leprosy in contacts of patients with leprosy? 2. What are the experiences and acceptability with the use of rifampin chemoprophylaxis in the prevention of disease from contacts with patients who have leprosy, in patients with leprosy following treatment and in family and health care professionals? Inclusion criteria Types of participants The quantitative and qualitative components of this evaluation will include individuals of both genders of any age who were intra-household or extra-household contacts (contacts from work, social contacts, neighbors or community) of leprosy patients diagnosed as new cases, recurring cases or abandonment of treatment who used rifampicin chemoprophylaxis. Those patients who received other chemoprophylaxis treatments such as dapsone, Acedapsone or treatments not associated with rifampicin will be excluded. The qualitative component will also include leprosy patients following treatment, family members and health care professionals who assisted those patients. Types of intervention(s)/phenomena of interest The quantitative component will consider studies that evaluated the effectiveness of rifampicin chemoprophylaxis at any dose, frequency, or administration and combination regimens such as single-dose, double-dose, Bacillus Calmette-Guerin vaccine combination and ROM combination. Comparison: placebo or chemoprophylactic regimens without rifampicin or no comparison The qualitative component of this review will consider studies that evaluated the experiences and acceptability of contacts of leprosy patients, patients with leprosy following treatment, family and health care professionals with the use of rifampicin such as single-dose, double-dose, Bacillus Calmette-Guerin vaccine combination and rifampicin, ofloxacin and minocycline regimen combination. Contexts that may be included but are not limited to consideration include household contact with leprosy and community and health service. Types of outcomes The quantitative component of the review will consider studies that have measured impact on the following outcomes using a range of measures: development of clinical leprosy in contacts of patients with leprosy (primary outcome), incidence rate, adverse effects and safety/harmful effects of rifampicin chemoprophylaxis. The qualitative component of the review will consider studies that related to individual experiences, acceptance, compliance, treatment refusal, medication adherence and satisfaction.