17-α Hydroxyprogesterone Nanoemulsifying Preconcentrate-Loaded Vaginal Tablet: A Novel Non-Invasive Approach for the Prevention of Preterm Birth
Preterm birth (PTB) is a major cause of infant mortality in the United States and around the globe. Makena<sup>®</sup>—once-a-week intramuscular injection of 17-α Hydroxyprogesterone caproate (17P)—is the only FDA approved treatment for the preventio...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/7/335 |
| _version_ | 1798039556644143104 |
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| author | Manali Patki Kiersten Giusto Samir Gorasiya Sandra E. Reznik Ketan Patel |
| author_facet | Manali Patki Kiersten Giusto Samir Gorasiya Sandra E. Reznik Ketan Patel |
| author_sort | Manali Patki |
| collection | DOAJ |
| description | Preterm birth (PTB) is a major cause of infant mortality in the United States and around the globe. Makena<sup>®</sup>—once-a-week intramuscular injection of 17-α Hydroxyprogesterone caproate (17P)—is the only FDA approved treatment for the prevention of PTB. Invasive delivery of 17P requires hospitalization and expert personnel for injection. Vaginal delivery of 17P would be preferable, because of high patient compliance, reduced systemic exposure, fewer side effects, and no need for hospitalization. The objective of the present study was to prepare and evaluate a self-nanoemulsifying vaginal tablet of 17P. A solid self-nanoemulsifying preconcentrate (S-SNEDDS) of 17P and dimethylacetamide (DMA) was developed using medium chain triglycerides, a non- immunogenic surfactant, and co-processed excipient (PVA-F100). The tablet prepared was characterized for emulsification time, particle size, solid state properties, and drug release. The formulation showed >50% inhibition of TNF-α release from LPS-stimulated RAW 264.7 cells. Importantly, there were significant differences in rates of PTB and average time to delivery between control and vaginal 17P-treated groups in LPS-stimulated timed pregnant E15.5 mice. Considering the lacuna of therapeutic approaches in this area, vaginal delivery of 17P for the prevention of preterm birth has significant clinical relevance. |
| first_indexed | 2024-04-11T21:55:31Z |
| format | Article |
| id | doaj.art-11291dec7bc143519a43d0bf16d27427 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T21:55:31Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-11291dec7bc143519a43d0bf16d274272022-12-22T04:01:07ZengMDPI AGPharmaceutics1999-49232019-07-0111733510.3390/pharmaceutics11070335pharmaceutics1107033517-α Hydroxyprogesterone Nanoemulsifying Preconcentrate-Loaded Vaginal Tablet: A Novel Non-Invasive Approach for the Prevention of Preterm BirthManali Patki0Kiersten Giusto1Samir Gorasiya2Sandra E. Reznik3Ketan Patel4Pharmaceutical Sciences, St. John’s University, Queens, NY 11439, USAPharmaceutical Sciences, St. John’s University, Queens, NY 11439, USAPharmaceutical Sciences, St. John’s University, Queens, NY 11439, USAPharmaceutical Sciences, St. John’s University, Queens, NY 11439, USAPharmaceutical Sciences, St. John’s University, Queens, NY 11439, USAPreterm birth (PTB) is a major cause of infant mortality in the United States and around the globe. Makena<sup>®</sup>—once-a-week intramuscular injection of 17-α Hydroxyprogesterone caproate (17P)—is the only FDA approved treatment for the prevention of PTB. Invasive delivery of 17P requires hospitalization and expert personnel for injection. Vaginal delivery of 17P would be preferable, because of high patient compliance, reduced systemic exposure, fewer side effects, and no need for hospitalization. The objective of the present study was to prepare and evaluate a self-nanoemulsifying vaginal tablet of 17P. A solid self-nanoemulsifying preconcentrate (S-SNEDDS) of 17P and dimethylacetamide (DMA) was developed using medium chain triglycerides, a non- immunogenic surfactant, and co-processed excipient (PVA-F100). The tablet prepared was characterized for emulsification time, particle size, solid state properties, and drug release. The formulation showed >50% inhibition of TNF-α release from LPS-stimulated RAW 264.7 cells. Importantly, there were significant differences in rates of PTB and average time to delivery between control and vaginal 17P-treated groups in LPS-stimulated timed pregnant E15.5 mice. Considering the lacuna of therapeutic approaches in this area, vaginal delivery of 17P for the prevention of preterm birth has significant clinical relevance.https://www.mdpi.com/1999-4923/11/7/33517-α hydroxyprogesterone caproatepreterm birthself-nanoemulsifying systempreterm laborvaginal deliverynanoparticlevaginal tablet |
| spellingShingle | Manali Patki Kiersten Giusto Samir Gorasiya Sandra E. Reznik Ketan Patel 17-α Hydroxyprogesterone Nanoemulsifying Preconcentrate-Loaded Vaginal Tablet: A Novel Non-Invasive Approach for the Prevention of Preterm Birth Pharmaceutics 17-α hydroxyprogesterone caproate preterm birth self-nanoemulsifying system preterm labor vaginal delivery nanoparticle vaginal tablet |
| title | 17-α Hydroxyprogesterone Nanoemulsifying Preconcentrate-Loaded Vaginal Tablet: A Novel Non-Invasive Approach for the Prevention of Preterm Birth |
| title_full | 17-α Hydroxyprogesterone Nanoemulsifying Preconcentrate-Loaded Vaginal Tablet: A Novel Non-Invasive Approach for the Prevention of Preterm Birth |
| title_fullStr | 17-α Hydroxyprogesterone Nanoemulsifying Preconcentrate-Loaded Vaginal Tablet: A Novel Non-Invasive Approach for the Prevention of Preterm Birth |
| title_full_unstemmed | 17-α Hydroxyprogesterone Nanoemulsifying Preconcentrate-Loaded Vaginal Tablet: A Novel Non-Invasive Approach for the Prevention of Preterm Birth |
| title_short | 17-α Hydroxyprogesterone Nanoemulsifying Preconcentrate-Loaded Vaginal Tablet: A Novel Non-Invasive Approach for the Prevention of Preterm Birth |
| title_sort | 17 α hydroxyprogesterone nanoemulsifying preconcentrate loaded vaginal tablet a novel non invasive approach for the prevention of preterm birth |
| topic | 17-α hydroxyprogesterone caproate preterm birth self-nanoemulsifying system preterm labor vaginal delivery nanoparticle vaginal tablet |
| url | https://www.mdpi.com/1999-4923/11/7/335 |
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