Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery
Brimonidine tartrate (BRT) is a highly selective α2 adrenergic receptor agonist as treatment for patients with open angle glaucoma and high intraocular pressure. The objective of this study was to formulate an ophthalmic ion-sensitive in situ gel (ISG) of BRT to increase the retention time of the dr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/1/90 |
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| author | Haonan Xu Ye Liu Lu Jin Xu Chen Xinghao Chen Qiao Wang Zhan Tang |
| author_facet | Haonan Xu Ye Liu Lu Jin Xu Chen Xinghao Chen Qiao Wang Zhan Tang |
| author_sort | Haonan Xu |
| collection | DOAJ |
| description | Brimonidine tartrate (BRT) is a highly selective α2 adrenergic receptor agonist as treatment for patients with open angle glaucoma and high intraocular pressure. The objective of this study was to formulate an ophthalmic ion-sensitive in situ gel (ISG) of BRT to increase the retention time of the drug and its bioavailability. The optimum formulation of 2 mg/mL BRT-ISG was obtained with 0.45% gellan gum as the gel matrix. In vitro release results showed that the water-soluble drug bromonidine tartrate in ocular in situ gels exhibited a high burst effect and fast release in solution. The results of dialysis membrane permeation showed that there was a significant difference between the commercially available and BRT-ISG groups after 45 min. The results of the pre-corneal retention study indicated that gellan gum can effectively prolong ocular surface retention. Preliminary stability results showed that it should be stored in a cool and dark place, and the formulation under long-term preservation can be basically stable. The pharmacokinetic study of the BRT-ISG in the anterior chamber of the rabbit eye was studied by microdialysis technique, and microdialysis samples were analyzed by LC-MS/MS. The pharmacokinetic study showed that the BRT-ISG reached Cmax (8.16 mg/L) at 93 min after administration, which was 2.7 times that of the BRT eye drops, and the AUC(0-t) (1397.08 mg·min/L) was 3.4 times that of the BRT eye drops. The optimal prescription can prolong the retention time of BRT in front of the cornea and significantly improve the bioavailability of BRT in the eye. Combined with the results of in vitro release, permeation and pre-corneal retention studies, the improvement of BRT-ISG bioavailability in rabbit eyes was found to be mainly due to the retention effect after the mixture of ISG and tears. |
| first_indexed | 2024-03-09T11:29:31Z |
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| id | doaj.art-6b2ce122c91947f88c3f9891ed912bea |
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| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T11:29:31Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-6b2ce122c91947f88c3f9891ed912bea2023-11-30T23:55:40ZengMDPI AGPharmaceuticals1424-82472023-01-011619010.3390/ph16010090Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular DeliveryHaonan Xu0Ye Liu1Lu Jin2Xu Chen3Xinghao Chen4Qiao Wang5Zhan Tang6School of Pharmacy, Hangzhou Medical College, Hangzhou 310013, ChinaSchool of Pharmacy, Hangzhou Medical College, Hangzhou 310013, ChinaSchool of Pharmacy, Hangzhou Medical College, Hangzhou 310013, ChinaSchool of Pharmacy, Hangzhou Medical College, Hangzhou 310013, ChinaSchool of Pharmacy, Hangzhou Medical College, Hangzhou 310013, ChinaSchool of Pharmacy, Hangzhou Medical College, Hangzhou 310013, ChinaSchool of Pharmacy, Hangzhou Medical College, Hangzhou 310013, ChinaBrimonidine tartrate (BRT) is a highly selective α2 adrenergic receptor agonist as treatment for patients with open angle glaucoma and high intraocular pressure. The objective of this study was to formulate an ophthalmic ion-sensitive in situ gel (ISG) of BRT to increase the retention time of the drug and its bioavailability. The optimum formulation of 2 mg/mL BRT-ISG was obtained with 0.45% gellan gum as the gel matrix. In vitro release results showed that the water-soluble drug bromonidine tartrate in ocular in situ gels exhibited a high burst effect and fast release in solution. The results of dialysis membrane permeation showed that there was a significant difference between the commercially available and BRT-ISG groups after 45 min. The results of the pre-corneal retention study indicated that gellan gum can effectively prolong ocular surface retention. Preliminary stability results showed that it should be stored in a cool and dark place, and the formulation under long-term preservation can be basically stable. The pharmacokinetic study of the BRT-ISG in the anterior chamber of the rabbit eye was studied by microdialysis technique, and microdialysis samples were analyzed by LC-MS/MS. The pharmacokinetic study showed that the BRT-ISG reached Cmax (8.16 mg/L) at 93 min after administration, which was 2.7 times that of the BRT eye drops, and the AUC(0-t) (1397.08 mg·min/L) was 3.4 times that of the BRT eye drops. The optimal prescription can prolong the retention time of BRT in front of the cornea and significantly improve the bioavailability of BRT in the eye. Combined with the results of in vitro release, permeation and pre-corneal retention studies, the improvement of BRT-ISG bioavailability in rabbit eyes was found to be mainly due to the retention effect after the mixture of ISG and tears.https://www.mdpi.com/1424-8247/16/1/90brimonidine tartratein-situ gelocular permeationmicrodialysis |
| spellingShingle | Haonan Xu Ye Liu Lu Jin Xu Chen Xinghao Chen Qiao Wang Zhan Tang Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery Pharmaceuticals brimonidine tartrate in-situ gel ocular permeation microdialysis |
| title | Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery |
| title_full | Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery |
| title_fullStr | Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery |
| title_full_unstemmed | Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery |
| title_short | Preparation and Characterization of Ion-Sensitive Brimonidine Tartrate In Situ Gel for Ocular Delivery |
| title_sort | preparation and characterization of ion sensitive brimonidine tartrate in situ gel for ocular delivery |
| topic | brimonidine tartrate in-situ gel ocular permeation microdialysis |
| url | https://www.mdpi.com/1424-8247/16/1/90 |
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