A thermodynamic relationship and phase transition study involving two polymorphs of sulfamethoxazole: form I <i>vs.</i> form II

Oliveira, Carlos Henrique de Moura; Freitas, Jennifer Tavares Jacon; Rosa, Iara M. L.

doi:10.1039/d1nj03597e

Cited by 3 publications

(2 citation statements)

References 72 publications

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“…The DSC heating curves of “as is” crystalline SMZ and TMP revealed endotherms, respectively, at 169 and 200 °C, attributable to melting (Figure S6). The melting temperatures and the enthalpy of fusion values were in excellent agreement with the literature. , The SMZ-TMP salt melted at 178 °C (Figure S6). The T g s of amorphous SMZ and TMP, at 30 and 59 °C, were followed by crystallization at 63 and 89 °C, respectively (Figure S7).…”

Section: Resultssupporting

confidence: 88%

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Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations

Duggirala

Kumar

et al. 2022

Mol. Pharmaceutics

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Using sulfamethoxazole (SMZ) and trimethoprim (TMP) as model drugs, we designed amorphous solid dispersions (ASDs) for the simultaneous solubility enhancement of two active pharmaceutical ingredients (APIs) by exploiting the drug–drug and drug–polymer interactions. In order to make this approach broadly applicable and over a wide dose range, a mixture of SMZ and TMP at weight ratios of 5:1 and 1:5 (w/w) were formulated into ternary ASDs. Depending on the dose ratio of the two drugs, the polymer used was either an aminoalkyl methacrylate copolymer (Eudragit, EDE) or polyacrylic acid. The drug–drug and drug–polymer interactions were characterized to be ionic by infrared and solid-state nuclear magnetic resonance spectroscopy. The interactions resulted in a substantial reduction in molecular mobility, evident from the increase in the structural relaxation time determined by dielectric spectroscopy. The drug–drug interaction resulted in ∼3 orders of magnitude reduction in molecular mobility. The addition of a polymer led to a further decrease in molecular mobility of up to 4 orders of magnitude. The strength of intermolecular interactions was also estimated from the glass transition temperatures of the ASDs obtained by differential scanning calorimetry. The strong intermolecular interactions yielded highly stable ASDs with no evidence of crystallization, both at elevated temperatures and under accelerated storage conditions (40 °C/75% relative humidity; 6 weeks). The dissolution performances of the ASDs were evaluated using the area under the curve (AUC) obtained from the concentration–time profiles under the non-sink condition. SMZ and TMP in their ternary ASDs, when compared with their crystalline counterparts, exhibited up to 6.4- and 4.6-fold increases in AUC, respectively. Importantly, the synchronized release of the two drugs was observed, a desirable attribute in synergistic formulations. A single-phase ternary ASD, stabilized by drug–drug and drug–polymer interactions, is likely responsible for the unique release profile.

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Section: Resultssupporting

confidence: 88%

“…The melting temperatures and the enthalpy of fusion values were in excellent agreement with the literature. 16,17 The SMZ-TMP salt melted at 178 °C (Figure S6). The T g s of amorphous SMZ and TMP, at 30 and 59 °C, were followed by crystallization at 63 and 89 °C, respectively (Figure S7).…”

Section: ■ Introductionmentioning

confidence: 99%

Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations

Duggirala

Kumar

et al. 2022

Mol. Pharmaceutics

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Polymorphism Dependent Cytotoxicity, Cellular Uptake, and Live Cell Imaging Studies on Napthalimide‐Vinyl‐Phenothiazine Conjugate

Munthasir,

Rani,

Dhanalakshmi

et al. 2024

Chemistry A European J

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Polymorphism‐dependent cytotoxicity and cellular uptake of drug molecules have been studied for the past two decades. However, visualizing the polymorph‐dependent cellular uptake and cytotoxicity using microscopy imaging technique has not been reported yet. The luminescent polymorph is an ideal candidate to validate the above hypothesis. Herein, we report the polymorph‐dependent cellular uptake, cytotoxicity, and bio‐imaging functions of polymorphs 1Y and 1R of a naphthalimide‐phenothiazine dyad. These polymorphs show different luminescence colors in the solid state and exhibit aggregation‐induced enhanced emission (AIEE) in the DMSO‐Water mixture. Bioimaging, cytotoxicity assay, and fluorescence‐activated cell sorting (FACS) studies revealed that these polymorphs show different levels of cytotoxicity, cellular uptake, localization, and imaging potential. Detailed photophysical, morphological, and biological studies revealed that the difference in molecular conformation in these polymorphs enables them to form aggregates of different sizes and morphology, which leads to the differential uptake of these into the cells and consequently shows different cytotoxicity and imaging potentials.

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Single-crystal-to-single-crystal phase transition of 18β-glycyrrhetinic acid isopropyl ester

Langer¹,

Wicher²,

Tykarska³

2022

Acta Crystallogr Sect B

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Due to the destruction of the integrity of the parent crystal, single-crystal-to-single-crystal phase transition in organic compounds is still a relatively rare phenomenon. The phase transition in glycyrrhetinic acid isopropyl ester is triggered by temperature change. The increasing volume of the isopropyl substituent as a result of increasing temperature forces a remodelling of the structural motifs. These changes cause a single-crystal-to-single-crystal phase transition. The low-temperature form is isostructural with glycyrrhetinic acid methanol solvate, while the high-temperature phase is isostructural with the ethyl ester of this acid.

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A thermodynamic relationship and phase transition study involving two polymorphs of sulfamethoxazole: form I vs. form II

Abstract: Two sulfamethoxazole polymorphs (form I and II) have been studied. The form II → form I transformation is observed via milling and dissolution in acetonitrile. A phase transition mechanism is proposed based on their supramolecular geometries.

Cited by 3 publications

References 72 publications

Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations

Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations

Polymorphism Dependent Cytotoxicity, Cellular Uptake, and Live Cell Imaging Studies on Napthalimide‐Vinyl‐Phenothiazine Conjugate

Single-crystal-to-single-crystal phase transition of 18β-glycyrrhetinic acid isopropyl ester

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