Publication: DEVELOPMENT AND PHARMACOKINETICS OF TINIDAZOLE INTRAVAGINAL CONTROLLED DELIVERY MATRICES FOR THE TREATMENT OF BACTERIAL VAGINOSIS
Date
2023
Authors
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Journal ISSN
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Publisher
International Medical University
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.
Description
Keywords
Polyethylene Glycols, Tinidazole, Vaginosis, Bacterial, Sexually Transmitted Diseases, Bacteria, Anaerobic