Simultaneous Improvement in Dissolution Behavior and Oral Bioavailability of Naproxen via Salt Formation
Naproxen (NAP) is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the arylpropionic acid class. Classified as a Biopharmaceutical Classification System (BCS) class II drug, NAP exhibits low water solubility, thus resulting in restricted oral bioavailability. This study aimed to evalua...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Crystals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4352/14/12/1104 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850042475850235904 |
|---|---|
| author | Xian-Rui Zhang Bao-Lin Wu Jing-Jing Han Jin-Qing Li |
| author_facet | Xian-Rui Zhang Bao-Lin Wu Jing-Jing Han Jin-Qing Li |
| author_sort | Xian-Rui Zhang |
| collection | DOAJ |
| description | Naproxen (NAP) is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the arylpropionic acid class. Classified as a Biopharmaceutical Classification System (BCS) class II drug, NAP exhibits low water solubility, thus resulting in restricted oral bioavailability. This study aimed to evaluate the effectiveness of pharmaceutical salts in enhancing the solubility and oral bioavailability of NAP. Two novel NAP salts, specifically naproxen-ethylenediamine (NAP-EDA) and naproxen-trometamol (NAP-TRIS), were synthesized using a 2:1 and 1:1 stoichiometric ratio, respectively. The NAP-EDA and NAP-TRIS powders were thoroughly characterized using single-crystal X-ray diffraction (SXRD), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC), providing a comprehensive understanding of their structural and thermal properties. Additionally, the solubilities and dissolution rates of NAP-EDA and NAP-TRIS salts were assessed in water and a pH 6.86 phosphate buffer. Notably, the solubility of NAP-TRIS salt increased markedly, by 397.5-fold in water and 6.2-fold at pH 6.86. Furthermore, in vivo pharmacokinetic studies in rats revealed that NAP-TRIS salt displayed faster absorption and higher peak blood concentrations compared to NAP. These results indicate that the NAP-TRIS salt effectively enhanced the solubility and oral bioavailability of naproxen. In conclusion, this study underscores the potential of pharmaceutical salts, particularly NAP-TRIS, in improving the solubility and oral bioavailability of drugs with low aqueous solubility, presenting a promising avenue for advancing drug delivery and therapeutic outcomes. |
| format | Article |
| id | doaj-art-30239deede334a68a22e5958439e6ec3 |
| institution | DOAJ |
| issn | 2073-4352 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj-art-30239deede334a68a22e5958439e6ec32025-08-20T02:55:32ZengMDPI AGCrystals2073-43522024-12-011412110410.3390/cryst14121104Simultaneous Improvement in Dissolution Behavior and Oral Bioavailability of Naproxen via Salt FormationXian-Rui Zhang0Bao-Lin Wu1Jing-Jing Han2Jin-Qing Li3College of Food and Pharmaceutical Engineering, Wuzhou University, Wuzhou 543000, ChinaGuangxi Wuzhou Zhongguan Inspection Technology Services Co., Limited, Wuzhou 543000, ChinaCollege of Food and Pharmaceutical Engineering, Wuzhou University, Wuzhou 543000, ChinaCollege of Food and Pharmaceutical Engineering, Wuzhou University, Wuzhou 543000, ChinaNaproxen (NAP) is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the arylpropionic acid class. Classified as a Biopharmaceutical Classification System (BCS) class II drug, NAP exhibits low water solubility, thus resulting in restricted oral bioavailability. This study aimed to evaluate the effectiveness of pharmaceutical salts in enhancing the solubility and oral bioavailability of NAP. Two novel NAP salts, specifically naproxen-ethylenediamine (NAP-EDA) and naproxen-trometamol (NAP-TRIS), were synthesized using a 2:1 and 1:1 stoichiometric ratio, respectively. The NAP-EDA and NAP-TRIS powders were thoroughly characterized using single-crystal X-ray diffraction (SXRD), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC), providing a comprehensive understanding of their structural and thermal properties. Additionally, the solubilities and dissolution rates of NAP-EDA and NAP-TRIS salts were assessed in water and a pH 6.86 phosphate buffer. Notably, the solubility of NAP-TRIS salt increased markedly, by 397.5-fold in water and 6.2-fold at pH 6.86. Furthermore, in vivo pharmacokinetic studies in rats revealed that NAP-TRIS salt displayed faster absorption and higher peak blood concentrations compared to NAP. These results indicate that the NAP-TRIS salt effectively enhanced the solubility and oral bioavailability of naproxen. In conclusion, this study underscores the potential of pharmaceutical salts, particularly NAP-TRIS, in improving the solubility and oral bioavailability of drugs with low aqueous solubility, presenting a promising avenue for advancing drug delivery and therapeutic outcomes.https://www.mdpi.com/2073-4352/14/12/1104naproxenethylenediaminetrometamolsaltsolubilitybioavailability |
| spellingShingle | Xian-Rui Zhang Bao-Lin Wu Jing-Jing Han Jin-Qing Li Simultaneous Improvement in Dissolution Behavior and Oral Bioavailability of Naproxen via Salt Formation Crystals naproxen ethylenediamine trometamol salt solubility bioavailability |
| title | Simultaneous Improvement in Dissolution Behavior and Oral Bioavailability of Naproxen via Salt Formation |
| title_full | Simultaneous Improvement in Dissolution Behavior and Oral Bioavailability of Naproxen via Salt Formation |
| title_fullStr | Simultaneous Improvement in Dissolution Behavior and Oral Bioavailability of Naproxen via Salt Formation |
| title_full_unstemmed | Simultaneous Improvement in Dissolution Behavior and Oral Bioavailability of Naproxen via Salt Formation |
| title_short | Simultaneous Improvement in Dissolution Behavior and Oral Bioavailability of Naproxen via Salt Formation |
| title_sort | simultaneous improvement in dissolution behavior and oral bioavailability of naproxen via salt formation |
| topic | naproxen ethylenediamine trometamol salt solubility bioavailability |
| url | https://www.mdpi.com/2073-4352/14/12/1104 |
| work_keys_str_mv | AT xianruizhang simultaneousimprovementindissolutionbehaviorandoralbioavailabilityofnaproxenviasaltformation AT baolinwu simultaneousimprovementindissolutionbehaviorandoralbioavailabilityofnaproxenviasaltformation AT jingjinghan simultaneousimprovementindissolutionbehaviorandoralbioavailabilityofnaproxenviasaltformation AT jinqingli simultaneousimprovementindissolutionbehaviorandoralbioavailabilityofnaproxenviasaltformation |