Abstract
Background: Induction of labour (IOL) is a widely-used practice in obstetrics to prevent maternal and fetal morbidity and mortality. However, a major complication of IOL is hyperstimulation of the uterus, which can lead to the sudden onset of powerful, frequent and painful contractions which women may find unbearable and frightening. These uterine contractions can damage the fetus due to hypoxia as the placenta cannot be fully revascularised if the uterus is contracting too frequently. Despite these concerns, there is increasing demand to deliver IOL in an outpatient setting where women can be more comfortable and relaxed and reduce their length of stay in hospital. Here, we describe a new IOL method involving slow and continuous administration of cervical ripening agents from intravaginal rings. This approach has the potential to more closely mimic the natural cervical ripening process and spontaneous onset of labour and reduce the incidence of hyperstimulation, making it safer for outpatient use and more acceptable to women. This study investigated the potential of using intravaginal rings to control the administration of isosorbide mononitrate (ISMN), a widely used cervical ripening agent.
Methods: Reservoir-type and orifice-type silicone elastomer intravaginal rings were prepared using injection-molding technologies. DSC testing was performed to study the possible interactions between the drug molecule and the silicone elastomer. In vitro drug release testing of the rings was performed in simulated vaginal fluid.
Results: The daily release of ISMN from all ring formulations were relatively constant over 14 days, representing linear cumulative release vs. time profiles. The release rate of ISMN was shown to depend upon the core length and the sheath compositions. Daily ISMN release rates of the half-core ring were half the values of the full-core ring, 2.49 vs 5.22 mg/day. There is no significant difference in the ISMN release rate for rings without sucrose in the sheath and the rings with 5% and 10% sucrose in the sheath, 5.22 vs. 4.77 vs. 5.30 mg/day. Compared with the conventional reservoir-type ring, the ring containing 20% sucrose and the orifice-type ring had faster release rates, which were 6.37 and 6.29 mg/day.
Conclusions: Intravaginal rings could control the administration of ISMN at a low and constant rate, indicating their potential for cervical ripening and induction of labour in an out-patient setting.
Methods: Reservoir-type and orifice-type silicone elastomer intravaginal rings were prepared using injection-molding technologies. DSC testing was performed to study the possible interactions between the drug molecule and the silicone elastomer. In vitro drug release testing of the rings was performed in simulated vaginal fluid.
Results: The daily release of ISMN from all ring formulations were relatively constant over 14 days, representing linear cumulative release vs. time profiles. The release rate of ISMN was shown to depend upon the core length and the sheath compositions. Daily ISMN release rates of the half-core ring were half the values of the full-core ring, 2.49 vs 5.22 mg/day. There is no significant difference in the ISMN release rate for rings without sucrose in the sheath and the rings with 5% and 10% sucrose in the sheath, 5.22 vs. 4.77 vs. 5.30 mg/day. Compared with the conventional reservoir-type ring, the ring containing 20% sucrose and the orifice-type ring had faster release rates, which were 6.37 and 6.29 mg/day.
Conclusions: Intravaginal rings could control the administration of ISMN at a low and constant rate, indicating their potential for cervical ripening and induction of labour in an out-patient setting.
Original language | English |
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Publication status | Published - 2018 |
Event | Global Health Symposium 2018 - Queen's University Belfast, Belfast, United Kingdom Duration: 26 Apr 2018 → 27 Apr 2018 http://ghs.qub.ac.uk |
Conference
Conference | Global Health Symposium 2018 |
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Abbreviated title | GHS2018 |
Country/Territory | United Kingdom |
City | Belfast |
Period | 26/04/2018 → 27/04/2018 |
Internet address |