Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate
Palbociclib (PAL) is an effective anti-breast cancer drug, but its use has been partly restricted due to poor bioavailability (resulting from extremely low water solubility) and serious adverse reactions. In this study, two cocrystals of PAL with resorcinol (RES) or orcinol (ORC) were prepared by ev...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/1/23 |
| _version_ | 1797491189356691456 |
|---|---|
| author | Chenxin Duan Wenwen Liu Yunwen Tao Feifei Liang Yanming Chen Xinyi Xiao Guisen Zhang Yin Chen Chao Hao |
| author_facet | Chenxin Duan Wenwen Liu Yunwen Tao Feifei Liang Yanming Chen Xinyi Xiao Guisen Zhang Yin Chen Chao Hao |
| author_sort | Chenxin Duan |
| collection | DOAJ |
| description | Palbociclib (PAL) is an effective anti-breast cancer drug, but its use has been partly restricted due to poor bioavailability (resulting from extremely low water solubility) and serious adverse reactions. In this study, two cocrystals of PAL with resorcinol (RES) or orcinol (ORC) were prepared by evaporation crystallization to enhance their solubility. The cocrystals were characterized by single crystal X-ray diffraction, Hirshfeld surface analysis, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared and scanning electron microscopy. The intrinsic dissolution rates of the PAL cocrystals were determined in three different dissolution media (pH 1.0, pH 4.5 and pH 6.8), and both cocrystals showed improved dissolution rates at pH 1.0 and pH 6.8 in comparison to the parent drug. In addition, the cocrystals increased the solubility of PAL at pH 6.8 by 2–3 times and showed good stabilities in both the accelerated stability testing and stress testing. The PAL-RES cocrystal also exhibited an improved relative bioavailability (1.24 times) than PAL in vivo pharmacokinetics in rats. Moreover, the in vitro cytotoxicity assay of PAL-RES showed an increased IC<sub>50</sub> value for normal cells, suggesting a better biosafety profile than PAL. Co-crystallization may represent a promising strategy for improving the physicochemical properties of PAL with better pharmacokinetics. |
| first_indexed | 2024-03-10T00:43:54Z |
| format | Article |
| id | doaj.art-29d16c6dbb004edf929ac8f0a8b5bb01 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T00:43:54Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-29d16c6dbb004edf929ac8f0a8b5bb012023-11-23T15:02:36ZengMDPI AGPharmaceutics1999-49232021-12-011412310.3390/pharmaceutics14010023Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution RateChenxin Duan0Wenwen Liu1Yunwen Tao2Feifei Liang3Yanming Chen4Xinyi Xiao5Guisen Zhang6Yin Chen7Chao Hao8Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaDepartment of Chemistry, Southern Methodist University, 3215 Daniel Avenue, Dallas, TX 75275-0314, USAJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaPalbociclib (PAL) is an effective anti-breast cancer drug, but its use has been partly restricted due to poor bioavailability (resulting from extremely low water solubility) and serious adverse reactions. In this study, two cocrystals of PAL with resorcinol (RES) or orcinol (ORC) were prepared by evaporation crystallization to enhance their solubility. The cocrystals were characterized by single crystal X-ray diffraction, Hirshfeld surface analysis, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared and scanning electron microscopy. The intrinsic dissolution rates of the PAL cocrystals were determined in three different dissolution media (pH 1.0, pH 4.5 and pH 6.8), and both cocrystals showed improved dissolution rates at pH 1.0 and pH 6.8 in comparison to the parent drug. In addition, the cocrystals increased the solubility of PAL at pH 6.8 by 2–3 times and showed good stabilities in both the accelerated stability testing and stress testing. The PAL-RES cocrystal also exhibited an improved relative bioavailability (1.24 times) than PAL in vivo pharmacokinetics in rats. Moreover, the in vitro cytotoxicity assay of PAL-RES showed an increased IC<sub>50</sub> value for normal cells, suggesting a better biosafety profile than PAL. Co-crystallization may represent a promising strategy for improving the physicochemical properties of PAL with better pharmacokinetics.https://www.mdpi.com/1999-4923/14/1/23palbociclibcocrystalHirshfeld surfacesolubilitydissolution ratephysical stability |
| spellingShingle | Chenxin Duan Wenwen Liu Yunwen Tao Feifei Liang Yanming Chen Xinyi Xiao Guisen Zhang Yin Chen Chao Hao Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate Pharmaceutics palbociclib cocrystal Hirshfeld surface solubility dissolution rate physical stability |
| title | Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate |
| title_full | Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate |
| title_fullStr | Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate |
| title_full_unstemmed | Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate |
| title_short | Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate |
| title_sort | two novel palbociclib resorcinol and palbociclib orcinol cocrystals with enhanced solubility and dissolution rate |
| topic | palbociclib cocrystal Hirshfeld surface solubility dissolution rate physical stability |
| url | https://www.mdpi.com/1999-4923/14/1/23 |
| work_keys_str_mv | AT chenxinduan twonovelpalbociclibresorcinolandpalbocicliborcinolcocrystalswithenhancedsolubilityanddissolutionrate AT wenwenliu twonovelpalbociclibresorcinolandpalbocicliborcinolcocrystalswithenhancedsolubilityanddissolutionrate AT yunwentao twonovelpalbociclibresorcinolandpalbocicliborcinolcocrystalswithenhancedsolubilityanddissolutionrate AT feifeiliang twonovelpalbociclibresorcinolandpalbocicliborcinolcocrystalswithenhancedsolubilityanddissolutionrate AT yanmingchen twonovelpalbociclibresorcinolandpalbocicliborcinolcocrystalswithenhancedsolubilityanddissolutionrate AT xinyixiao twonovelpalbociclibresorcinolandpalbocicliborcinolcocrystalswithenhancedsolubilityanddissolutionrate AT guisenzhang twonovelpalbociclibresorcinolandpalbocicliborcinolcocrystalswithenhancedsolubilityanddissolutionrate AT yinchen twonovelpalbociclibresorcinolandpalbocicliborcinolcocrystalswithenhancedsolubilityanddissolutionrate AT chaohao twonovelpalbociclibresorcinolandpalbocicliborcinolcocrystalswithenhancedsolubilityanddissolutionrate |