The Development of Super-Saturated Rebamipide Eye Drops for Enhanced Solubility, Stability, Patient Compliance, and Bioavailability
The present study aimed to develop clear aqueous rebamipide (REB) eye drops to enhance solubility, stability, patient compliance, and bioavailability. For the preparation of a super-saturated 1.5% REB solution, the pH-modification method using NaOH and a hydrophilic polymer was employed. Low-viscosi...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/3/950 |
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| author | Dong-Jin Jang Jun Hak Lee Da Hun Kim Jin-Woo Kim Tae-Sung Koo Kwan Hyung Cho |
| author_facet | Dong-Jin Jang Jun Hak Lee Da Hun Kim Jin-Woo Kim Tae-Sung Koo Kwan Hyung Cho |
| author_sort | Dong-Jin Jang |
| collection | DOAJ |
| description | The present study aimed to develop clear aqueous rebamipide (REB) eye drops to enhance solubility, stability, patient compliance, and bioavailability. For the preparation of a super-saturated 1.5% REB solution, the pH-modification method using NaOH and a hydrophilic polymer was employed. Low-viscosity hydroxypropyl methylcellulose (HPMC 4.5cp) was selected and worked efficiently to suppress REB precipitation at 40 °C for 16 days. The additionally optimized eye drops formulation (F18 and F19) using aminocaproic acid and D-sorbitol as a buffering agent and an osmotic agent, respectively, demonstrated long-term physicochemical stability at 25 °C and 40 °C for 6 months. The hypotonicity (<230 mOsm) for F18 and F19 noticeably extended the stable period, since the pressure causing the REB precipitation was relieved compared to the isotonic. In the rat study, the optimized REB eye drops showed significantly long-lasting pharmacokinetic results, suggesting the possibility of reducing daily administration times and increasing patient compliance (0.50- and 0.83-times lower C<sub>max</sub> and 2.60- and 3.64-times higher exposure in the cornea and aqueous humor). In conclusion, the formulations suggested in the present study are promising candidates and offer enhanced solubility, stability, patient compliance, and bioavailability. |
| first_indexed | 2024-03-11T06:01:52Z |
| format | Article |
| id | doaj.art-19ccce13c09a403cada5c6402bfb58e1 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:01:52Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-19ccce13c09a403cada5c6402bfb58e12023-11-17T13:16:41ZengMDPI AGPharmaceutics1999-49232023-03-0115395010.3390/pharmaceutics15030950The Development of Super-Saturated Rebamipide Eye Drops for Enhanced Solubility, Stability, Patient Compliance, and BioavailabilityDong-Jin Jang0Jun Hak Lee1Da Hun Kim2Jin-Woo Kim3Tae-Sung Koo4Kwan Hyung Cho5Department of Bio-Health Technology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae 50834, Republic of KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae 50834, Republic of KoreaGraduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Republic of KoreaGraduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Republic of KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae 50834, Republic of KoreaThe present study aimed to develop clear aqueous rebamipide (REB) eye drops to enhance solubility, stability, patient compliance, and bioavailability. For the preparation of a super-saturated 1.5% REB solution, the pH-modification method using NaOH and a hydrophilic polymer was employed. Low-viscosity hydroxypropyl methylcellulose (HPMC 4.5cp) was selected and worked efficiently to suppress REB precipitation at 40 °C for 16 days. The additionally optimized eye drops formulation (F18 and F19) using aminocaproic acid and D-sorbitol as a buffering agent and an osmotic agent, respectively, demonstrated long-term physicochemical stability at 25 °C and 40 °C for 6 months. The hypotonicity (<230 mOsm) for F18 and F19 noticeably extended the stable period, since the pressure causing the REB precipitation was relieved compared to the isotonic. In the rat study, the optimized REB eye drops showed significantly long-lasting pharmacokinetic results, suggesting the possibility of reducing daily administration times and increasing patient compliance (0.50- and 0.83-times lower C<sub>max</sub> and 2.60- and 3.64-times higher exposure in the cornea and aqueous humor). In conclusion, the formulations suggested in the present study are promising candidates and offer enhanced solubility, stability, patient compliance, and bioavailability.https://www.mdpi.com/1999-4923/15/3/950rebamipidesuper-saturated eye dropphysical stabilityophthalmic bioavailability |
| spellingShingle | Dong-Jin Jang Jun Hak Lee Da Hun Kim Jin-Woo Kim Tae-Sung Koo Kwan Hyung Cho The Development of Super-Saturated Rebamipide Eye Drops for Enhanced Solubility, Stability, Patient Compliance, and Bioavailability Pharmaceutics rebamipide super-saturated eye drop physical stability ophthalmic bioavailability |
| title | The Development of Super-Saturated Rebamipide Eye Drops for Enhanced Solubility, Stability, Patient Compliance, and Bioavailability |
| title_full | The Development of Super-Saturated Rebamipide Eye Drops for Enhanced Solubility, Stability, Patient Compliance, and Bioavailability |
| title_fullStr | The Development of Super-Saturated Rebamipide Eye Drops for Enhanced Solubility, Stability, Patient Compliance, and Bioavailability |
| title_full_unstemmed | The Development of Super-Saturated Rebamipide Eye Drops for Enhanced Solubility, Stability, Patient Compliance, and Bioavailability |
| title_short | The Development of Super-Saturated Rebamipide Eye Drops for Enhanced Solubility, Stability, Patient Compliance, and Bioavailability |
| title_sort | development of super saturated rebamipide eye drops for enhanced solubility stability patient compliance and bioavailability |
| topic | rebamipide super-saturated eye drop physical stability ophthalmic bioavailability |
| url | https://www.mdpi.com/1999-4923/15/3/950 |
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