Publication: DEVELOPMENT AND PHARMACOKINETICS OF TINIDAZOLE INTRAVAGINAL CONTROLLED DELIVERY MATRICES FOR THE TREATMENT OF BACTERIAL VAGINOSIS
| dc.contributor.author | SURESH SHANMUGHAM | |
| dc.date.accessioned | 2024-03-10T07:24:26Z | |
| dc.date.available | 2024-03-10T07:24:26Z | |
| dc.date.issued | 2023 | |
| dc.description.abstract | The current study investigated the potential of Poly (e-caprolactone)/Polyethylene oxide (PCL/PEO) based intravaginal matrices for the controlled delivery of tinidazole in the therapy of bacterial vaginosis. PCL/PEO matrices loaded with the microbicide tinidazole (TD) were produced by rapidly cooling suspensions of drug powder in PCL/PEO solutions in acetone to −80ºC. The prepared matrices were investigated for their morphology, drug-polymer compatibility, thermal properties and in vitro drug release. The actual tinidazole loadings were 1.1% to 3.8% w/w related to a theoretical loading of 10% w/w, and the drug incorporation efficiency was up to 38%. In vitro release studies showed a ‘burst release’ of 35-74% tinidazole in the first 24 hours and a cumulative release of 50-100% tinidazole in seven days. The released tinidazole displays up to 79% antibacterial activity against Gardnerella vaginalis. The in vivo rabbit pharmacokinetic study demonstrated the controlled release of tinidazole from the surgically sutured IVR segment. The mean tinidazole concentration in vaginal secretions on day 1 and day 3 was found to be 2303.6 ± 1485.08 ng/mL and 1627.6 ± 981.71 ng/mL respectively. The mean tinidazole concentrations in proximal and distal vaginal tissues on day 3 were found to be 792±182.43 and 689.5±135.05 ng/g respectively. Serum levels below the lower limit of quantification (0.5 μg/mL), show the controlled release of TD from the matrices, which may limit drug absorption into the systemic circulation and lower resistance risk. The results of the histopathological analysis showed that one week of intravaginal implants with and without tinidazole was well tolerated, had no significant effect on the histological morphology of the rabbit vagina, and no macroscopic changes were observed. These results demonstrate that PCL/PEO based intravaginal ring (IVR) has all the potential for the controlled intravaginal delivery of TD in bacterial vaginosis and warrants further investigation. | |
| dc.identifier.uri | https://hdl.handle.net/20.500.14377/36083 | |
| dc.language.iso | en | |
| dc.publisher | International Medical University | |
| dc.subject | Polyethylene Glycols | |
| dc.subject | Tinidazole | |
| dc.subject | Vaginosis, Bacterial | |
| dc.subject | Sexually Transmitted Diseases | |
| dc.subject | Bacteria, Anaerobic | |
| dc.title | DEVELOPMENT AND PHARMACOKINETICS OF TINIDAZOLE INTRAVAGINAL CONTROLLED DELIVERY MATRICES FOR THE TREATMENT OF BACTERIAL VAGINOSIS | |
| dc.type | Thesis | |
| dspace.entity.type | Publication | |
| oairecerif.author.affiliation | #PLACEHOLDER_PARENT_METADATA_VALUE# |