Conformational polymorphs of isotretinoin and their impact on physicochemical and biological properties

Cheng, Yinxiang; Rong, Xiaoyi; Xia, Min; Zhang, Zaiyong; Wang, Jianrong; Mei, Xuefeng

doi:10.1016/j.ijpharm.2021.121222

Cited by 5 publications

(10 citation statements)

References 36 publications

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“…The different conformational structures may explain the stability differences between ITT and cocrystals. In the previous studies, we found a new conformational polymorph of ITT (form II) with the s-cis conformation that is opposite to the commercially available ITT with s-trans conformation (form I). The s - cis conformation presents better thermal stability.…”

Section: Resultsmentioning

confidence: 83%

“…It means that ITT has a higher conjugation extent. It was reported that the major degradation products of retinoids are generated by the oxidation of their double bonds under heat and air. , The free radical intermediates are produced under the exposure of oxygen resulting in the degradation of epoxidation. ,− The high conjugation extent of ITT is conducive to the stable existence of free radicals and subsequent oxidation degradation. Hence, the cocrystals which possess a lower conjugation extent are more stable under the stressed condition.…”

Section: Resultsmentioning

confidence: 99%

“…To explore the dissolution behavior and bioavailability of cocrystal formulation, the ITT-ENT capsules were prepared by physically mixing the cocrystal and the excipients listed in Table S2. During the previous research on the absorption of ITT polymorphs, we discovered that the pH 4.5 dissolution condition is more pertinent to in vivo performance . In pH 4.5 buffer solution containing 0.2% lauryl dimethyl amine oxide, the in vitro release behaviors of commercial soft capsules and ITT-ENT capsules were evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…In the previous study, we found new conformational polymorphs of isotretinoin . To further improve the physicochemical properties, we aim to screen the cocrystals of ITT by the synthon design of carboxylic acids.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Improving the Stability, Dissolution, and Bioavailability of Isotretinoin by Cocrystallization

Cheng

Jiang

Zhang

et al. 2022

Crystal Growth & Design

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Isotretinoin (13-cis retinoic acid, ITT) is a gold standard therapy for the treatment of severe acne. However, because of its poor absorption, ITT must be taken with fatty meals to increase bioavailability. The coadministration of food could reduce the compliance of patients and increase the risk of inconsistent serum levels because of different eating habits. In this work, we designed and synthesized four cocrystals of ITT. The cocrystal between ITT and ethyl nicotinate (ENT), namely, ITT-ENT, presented better chemical stability, dissolution, and absorption than ITT itself. The AUC 0−10h of ITT-ENT cocrystal capsules is 2.6 times as that of the commercially available ITT capsules in the fasted state. Because of the high bioavailability in the fasted state, the food has a marginal effect on the absorption of cocrystal capsules. This work sets a good example for applying cocrystal technology to enhance the absorption and mitigate the food effect of drugs.

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Section: Resultsmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Improving the Stability, Dissolution, and Bioavailability of Isotretinoin by Cocrystallization

Cheng

Jiang

Zhang

et al. 2022

Crystal Growth & Design

Self Cite

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“…The solubility is one of the most important physicochemical properties for a drug to achieve a desired concentration in systemic circulation [ 65 ]. As a BCS Class II compound, the absorption of BEX is limited by its low solubility.…”

Section: Resultsmentioning

confidence: 99%

Cocrystal Prediction of Bexarotene by Graph Convolution Network and Bioavailability Improvement

Cheng

Wang

et al. 2022

Pharmaceutics

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Bexarotene (BEX) was approved by the FDA in 1999 for the treatment of cutaneous T-cell lymphoma (CTCL). The poor aqueous solubility causes the low bioavailability of the drug and thereby limits the clinical application. In this study, we developed a GCN-based deep learning model (CocrystalGCN) for in-silico screening of the cocrystals of BEX. The results show that our model obtained high performance relative to baseline models. The top 30 of 109 coformer candidates were scored by CocrystalGCN and then validated experimentally. Finally, cocrystals of BEX-pyrazine, BEX-2,5-dimethylpyrazine, BEX-methyl isonicotinate, and BEX-ethyl isonicotinate were successfully obtained. The crystal structures were determined by single-crystal X-ray diffraction. Powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis were utilized to characterize these multi-component forms. All cocrystals present superior solubility and dissolution over the parent drug. The pharmacokinetic studies show that the plasma exposures (AUC0−8h) of BEX-pyrazine and BEX-2,5-dimethylpyrazine are 1.7 and 1.8 times that of the commercially available BEX powder, respectively. This work sets a good example for integrating virtual prediction and experimental screening to discover the new cocrystals of water-insoluble drugs.

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Quantum chemical computational analysis, electronic transitions, interaction mechanisms analysis by spectroscopic, molecular docking, and molecular dynamic simulation of retinol

Jeba Reeda,

Divya,

Karthick

et al. 2024

Spectroscopy Letters

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Conformational polymorphs of isotretinoin and their impact on physicochemical and biological properties

Cited by 5 publications

References 36 publications

Improving the Stability, Dissolution, and Bioavailability of Isotretinoin by Cocrystallization

Improving the Stability, Dissolution, and Bioavailability of Isotretinoin by Cocrystallization

Cocrystal Prediction of Bexarotene by Graph Convolution Network and Bioavailability Improvement

Quantum chemical computational analysis, electronic transitions, interaction mechanisms analysis by spectroscopic, molecular docking, and molecular dynamic simulation of retinol

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