ENHANCE THE AQUEOUS SOLUBILITY OF DICLOFENAC THROUGH THE SYNTHESIS OF DICLOFENAC-INOSITOL PRODRUG
Due to limited aqueous solubility, poor bioavailability makes oral dosage formulations difficult to formulate. Chemical alteration of medicinal compounds improves solubility. Prodrug design is a popular molecular modification method that improves solubility and oral bioavailability. This study aims...
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University of Zakho
2024-11-01
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| Series: | Science Journal of University of Zakho |
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| Online Access: | http://sjuoz.uoz.edu.krd/index.php/sjuoz/article/view/1360 |
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| author | Hemn Latif Qader Omar Abdulrahman alsheikhly Hewa Abdulla Hamadameen Hama Adnan Burhan Qader |
| author_facet | Hemn Latif Qader Omar Abdulrahman alsheikhly Hewa Abdulla Hamadameen Hama Adnan Burhan Qader |
| author_sort | Hemn Latif Qader |
| collection | DOAJ |
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Due to limited aqueous solubility, poor bioavailability makes oral dosage formulations difficult to formulate. Chemical alteration of medicinal compounds improves solubility. Prodrug design is a popular molecular modification method that improves solubility and oral bioavailability. This study aims to synthesize a diclofenac prodrug to enhance aqueous solubility. In this study, diclofenac was esterified with inositol to make a prodrug (DIP), which was identified by 1H-NMR and FT-IR. A computational pharmacokinetic software was used to study DIP's pharmacokinetic profile, and saturation solubility was measured in phosphate buffer (pH 6.8) and 0.1 HCl (pH 1.2) solutions. The ester bands of (C=O) stretch at 1739 cm-1 and the elimination of H signals of carboxylic acid at 10-12 ppm in the 1H-NMR spectrum proved the synthesis of (DIP). Diclofenac solubility increased 827-fold in phosphate buffer solution (p < 0.05) from 0.059± 0.0164 mg/ml to 48.8± 0.034 mg/ml, primarily due to polarity change. The solubility of diclofenac and (DIP) in 0.1 N HCl (pH 1.2) was 0.016± 0.0031 and 0.018± 0.002, respectively. The improvement in solubility in the acidic medium was non-significant (p > 0.05) due to acid hydrolysis of the ester bond between inositol and the drug. The synthesis of diclofenac prodrug can greatly enhance its water solubility.
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| format | Article |
| id | doaj-art-c54777722e1c49b19c46898dad67b738 |
| institution | Kabale University |
| issn | 2663-628X 2663-6298 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | University of Zakho |
| record_format | Article |
| series | Science Journal of University of Zakho |
| spelling | doaj-art-c54777722e1c49b19c46898dad67b7382024-11-12T01:35:14ZengUniversity of ZakhoScience Journal of University of Zakho2663-628X2663-62982024-11-0112410.25271/sjuoz.2024.12.4.1360ENHANCE THE AQUEOUS SOLUBILITY OF DICLOFENAC THROUGH THE SYNTHESIS OF DICLOFENAC-INOSITOL PRODRUG Hemn Latif Qader0Omar Abdulrahman alsheikhly1Hewa Abdulla Hamadameen Hama2Adnan Burhan Qader3Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, Iraq Department of Pharmaceutical Chemistry, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, Iraqrtment of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, Iraq Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, Iraq Due to limited aqueous solubility, poor bioavailability makes oral dosage formulations difficult to formulate. Chemical alteration of medicinal compounds improves solubility. Prodrug design is a popular molecular modification method that improves solubility and oral bioavailability. This study aims to synthesize a diclofenac prodrug to enhance aqueous solubility. In this study, diclofenac was esterified with inositol to make a prodrug (DIP), which was identified by 1H-NMR and FT-IR. A computational pharmacokinetic software was used to study DIP's pharmacokinetic profile, and saturation solubility was measured in phosphate buffer (pH 6.8) and 0.1 HCl (pH 1.2) solutions. The ester bands of (C=O) stretch at 1739 cm-1 and the elimination of H signals of carboxylic acid at 10-12 ppm in the 1H-NMR spectrum proved the synthesis of (DIP). Diclofenac solubility increased 827-fold in phosphate buffer solution (p < 0.05) from 0.059± 0.0164 mg/ml to 48.8± 0.034 mg/ml, primarily due to polarity change. The solubility of diclofenac and (DIP) in 0.1 N HCl (pH 1.2) was 0.016± 0.0031 and 0.018± 0.002, respectively. The improvement in solubility in the acidic medium was non-significant (p > 0.05) due to acid hydrolysis of the ester bond between inositol and the drug. The synthesis of diclofenac prodrug can greatly enhance its water solubility. http://sjuoz.uoz.edu.krd/index.php/sjuoz/article/view/1360Aqueous solubilityDiclofenacesterification reactioninositolprodrug |
| spellingShingle | Hemn Latif Qader Omar Abdulrahman alsheikhly Hewa Abdulla Hamadameen Hama Adnan Burhan Qader ENHANCE THE AQUEOUS SOLUBILITY OF DICLOFENAC THROUGH THE SYNTHESIS OF DICLOFENAC-INOSITOL PRODRUG Science Journal of University of Zakho Aqueous solubility Diclofenac esterification reaction inositol prodrug |
| title | ENHANCE THE AQUEOUS SOLUBILITY OF DICLOFENAC THROUGH THE SYNTHESIS OF DICLOFENAC-INOSITOL PRODRUG |
| title_full | ENHANCE THE AQUEOUS SOLUBILITY OF DICLOFENAC THROUGH THE SYNTHESIS OF DICLOFENAC-INOSITOL PRODRUG |
| title_fullStr | ENHANCE THE AQUEOUS SOLUBILITY OF DICLOFENAC THROUGH THE SYNTHESIS OF DICLOFENAC-INOSITOL PRODRUG |
| title_full_unstemmed | ENHANCE THE AQUEOUS SOLUBILITY OF DICLOFENAC THROUGH THE SYNTHESIS OF DICLOFENAC-INOSITOL PRODRUG |
| title_short | ENHANCE THE AQUEOUS SOLUBILITY OF DICLOFENAC THROUGH THE SYNTHESIS OF DICLOFENAC-INOSITOL PRODRUG |
| title_sort | enhance the aqueous solubility of diclofenac through the synthesis of diclofenac inositol prodrug |
| topic | Aqueous solubility Diclofenac esterification reaction inositol prodrug |
| url | http://sjuoz.uoz.edu.krd/index.php/sjuoz/article/view/1360 |
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