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Thermoplastic polyurethane-based intravaginal rings for prophylaxis and treatment of (recurrent) bacterial vaginosis

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Abstract
The aim of the present study was to develop thermoplastic polyurethane (TPU)-based intravaginal rings (IVRs) for prophylaxis and treatment of bacterial vaginosis via hot melt extrusion/injection molding. Therefore, different TPU grades were processed in combination with lactic acid or metronidazole, targeting a sustained lactic acid release over a 28 day-period and sustained metronidazole release over 47 days. Hot melt extrusion of lactic acid/TPU combinations required a lower extrusion temperature due to the plasticizing properties of lactic acid, evidenced by the lower glass transition temperature (T-g) and cross-over point (T-tan delta (=) (1)) values. NIR-chemical imaging data showed a homogenous distribution of lactic acid in TPU matrices at drug loads up to 30% (w/w). The addition of metronidazole did not lower processing temperatures, as the active pharmaceutical ingredient remained crystalline in the TPU matrix. Hydrophobic TPUs with a low ratio between the soft and hard segments (SS/HS ratio) in the polymer structure were suitable carriers for the lactic acid-eluting device over a 28-day period, while hydrophilic TPUs were needed to achieve the required release rate of metronidazole-eluting IVRs. IVRs manufactured with a TPU grade having a higher SS/HS ratio and lactic acid/TPU ratio exhibited a more elastic behavior. The addition of 25% (w/w) metronidazole did not affect the mechanical properties of the IVRs. Hydrophilic TPUs were most prone to biofilm formation by Candida albicans and Staphylococcus aureus, but the incorporation of metronidazole in the device prevented biofilm formation. Based on the drug eluting performance and mechanical tests, a mixture of lactic acid and Tecoflex (TM) EG-93A (20/80, w/w) and a combination of metronidazole and Tecophilic (TM) SP-93A-100 (25/75, w/w) were selected to design IVRs for the prophylaxis and treatment of bacterial vaginosis, respectively. Slug mucosal irritation tests predicted low irritation potency for both devices. (C) 2017 Elsevier B.V. All rights reserved.
Keywords
CONTRACEPTIVE VAGINAL RING, LOCAL TOLERANCE, METRONIDAZOLE, DELIVERY, RELEASE, DRUG, FORMULATIONS, DAPIVIRINE, ADHERENCE, MATRICES, Hot melt extrusion, Intravaginal rings, Bacterial vaginosis, Thermoplastic polyurethanes, Lactic acid, Metronidazole

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MLA
Verstraete, Glenn et al. “Thermoplastic Polyurethane-based Intravaginal Rings for Prophylaxis and Treatment of (recurrent) Bacterial Vaginosis.” INTERNATIONAL JOURNAL OF PHARMACEUTICS 529.1-2 (2017): 218–226. Print.
APA
Verstraete, Glenn, Vandenbussche, L., Kasmi, S., Nuhn, L., Brouckaert, D., Van Renterghem, J., Grymonpre, W., et al. (2017). Thermoplastic polyurethane-based intravaginal rings for prophylaxis and treatment of (recurrent) bacterial vaginosis. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 529(1-2), 218–226.
Chicago author-date
Verstraete, Glenn, L. Vandenbussche, Sabah Kasmi, Lutz Nuhn, D. Brouckaert, Jeroen Van Renterghem, W. Grymonpre, et al. 2017. “Thermoplastic Polyurethane-based Intravaginal Rings for Prophylaxis and Treatment of (recurrent) Bacterial Vaginosis.” International Journal of Pharmaceutics 529 (1-2): 218–226.
Chicago author-date (all authors)
Verstraete, Glenn, L. Vandenbussche, Sabah Kasmi, Lutz Nuhn, D. Brouckaert, Jeroen Van Renterghem, W. Grymonpre, Valérie Vanhoorne, Tom Coenye, Bruno De Geest, Thomas De Beer, Jean Paul Remon, and Chris Vervaet. 2017. “Thermoplastic Polyurethane-based Intravaginal Rings for Prophylaxis and Treatment of (recurrent) Bacterial Vaginosis.” International Journal of Pharmaceutics 529 (1-2): 218–226.
Vancouver
1.
Verstraete G, Vandenbussche L, Kasmi S, Nuhn L, Brouckaert D, Van Renterghem J, et al. Thermoplastic polyurethane-based intravaginal rings for prophylaxis and treatment of (recurrent) bacterial vaginosis. INTERNATIONAL JOURNAL OF PHARMACEUTICS. 2017;529(1-2):218–26.
IEEE
[1]
G. Verstraete et al., “Thermoplastic polyurethane-based intravaginal rings for prophylaxis and treatment of (recurrent) bacterial vaginosis,” INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 529, no. 1–2, pp. 218–226, 2017.
@article{8625457,
  abstract     = {The aim of the present study was to develop thermoplastic polyurethane (TPU)-based intravaginal rings (IVRs) for prophylaxis and treatment of bacterial vaginosis via hot melt extrusion/injection molding. Therefore, different TPU grades were processed in combination with lactic acid or metronidazole, targeting a sustained lactic acid release over a 28 day-period and sustained metronidazole release over 47 days. Hot melt extrusion of lactic acid/TPU combinations required a lower extrusion temperature due to the plasticizing properties of lactic acid, evidenced by the lower glass transition temperature (T-g) and cross-over point (T-tan delta (=) (1)) values. NIR-chemical imaging data showed a homogenous distribution of lactic acid in TPU matrices at drug loads up to 30% (w/w). The addition of metronidazole did not lower processing temperatures, as the active pharmaceutical ingredient remained crystalline in the TPU matrix. Hydrophobic TPUs with a low ratio between the soft and hard segments (SS/HS ratio) in the polymer structure were suitable carriers for the lactic acid-eluting device over a 28-day period, while hydrophilic TPUs were needed to achieve the required release rate of metronidazole-eluting IVRs. IVRs manufactured with a TPU grade having a higher SS/HS ratio and lactic acid/TPU ratio exhibited a more elastic behavior. The addition of 25% (w/w) metronidazole did not affect the mechanical properties of the IVRs. Hydrophilic TPUs were most prone to biofilm formation by Candida albicans and Staphylococcus aureus, but the incorporation of metronidazole in the device prevented biofilm formation. Based on the drug eluting performance and mechanical tests, a mixture of lactic acid and Tecoflex (TM) EG-93A (20/80, w/w) and a combination of metronidazole and Tecophilic (TM) SP-93A-100 (25/75, w/w) were selected to design IVRs for the prophylaxis and treatment of bacterial vaginosis, respectively. Slug mucosal irritation tests predicted low irritation potency for both devices. (C) 2017 Elsevier B.V. All rights reserved.},
  author       = {Verstraete, Glenn and Vandenbussche, L. and Kasmi, Sabah and Nuhn, Lutz and Brouckaert, D. and Van Renterghem, Jeroen and Grymonpre, W. and Vanhoorne, Valérie and Coenye, Tom and De Geest, Bruno and De Beer, Thomas and Remon, Jean Paul and Vervaet, Chris},
  issn         = {0378-5173},
  journal      = {INTERNATIONAL JOURNAL OF PHARMACEUTICS},
  keywords     = {CONTRACEPTIVE VAGINAL RING,LOCAL TOLERANCE,METRONIDAZOLE,DELIVERY,RELEASE,DRUG,FORMULATIONS,DAPIVIRINE,ADHERENCE,MATRICES,Hot melt extrusion,Intravaginal rings,Bacterial vaginosis,Thermoplastic polyurethanes,Lactic acid,Metronidazole},
  language     = {eng},
  number       = {1-2},
  pages        = {218--226},
  title        = {Thermoplastic polyurethane-based intravaginal rings for prophylaxis and treatment of (recurrent) bacterial vaginosis},
  url          = {http://dx.doi.org/10.1016/j.ijpharm.2017.06.076},
  volume       = {529},
  year         = {2017},
}

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