17-α hydroxyprogesterone nanoemulsifying preconcentrate-loaded vaginal tablet: A novel non-invasive approach for the prevention of preterm birth

Manali Patki, Kiersten Giusto, Samir Gorasiya, Sandra E. Reznik, Ketan Patel

Research output: Contribution to journalArticle

Abstract

Preterm birth (PTB) is a major cause of infant mortality in the United States and around the globe. Makena®—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.

Original languageEnglish (US)
Article number335
JournalPharmaceutics
Volume11
Issue number7
DOIs
StatePublished - Jul 2019

Fingerprint

Foams and Jellies Vaginal Creams
17-alpha-Hydroxyprogesterone
Premature Obstetric Labor
Premature Birth
Nanoparticles
Hospitalization
Excipients
Intramuscular Injections
Infant Mortality
Patient Compliance
Particle Size
Surface-Active Agents
Tablets
Triglycerides
Tumor Necrosis Factor-alpha
Injections
17-alpha-hydroxy-progesterone caproate
Therapeutics

Keywords

  • 17-α hydroxyprogesterone caproate
  • Nanoparticle
  • Preterm birth
  • Preterm labor
  • Self-nanoemulsifying system
  • Vaginal delivery
  • Vaginal tablet

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

17-α hydroxyprogesterone nanoemulsifying preconcentrate-loaded vaginal tablet : A novel non-invasive approach for the prevention of preterm birth. / Patki, Manali; Giusto, Kiersten; Gorasiya, Samir; Reznik, Sandra E.; Patel, Ketan.

In: Pharmaceutics, Vol. 11, No. 7, 335, 07.2019.

Research output: Contribution to journalArticle

@article{31f16a909b194bdba761ca594f6f7da2,
title = "17-α hydroxyprogesterone nanoemulsifying preconcentrate-loaded vaginal tablet: A novel non-invasive approach for the prevention of preterm birth",
abstract = "Preterm birth (PTB) is a major cause of infant mortality in the United States and around the globe. Makena{\circledR}—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.",
keywords = "17-α hydroxyprogesterone caproate, Nanoparticle, Preterm birth, Preterm labor, Self-nanoemulsifying system, Vaginal delivery, Vaginal tablet",
author = "Manali Patki and Kiersten Giusto and Samir Gorasiya and Reznik, {Sandra E.} and Ketan Patel",
year = "2019",
month = "7",
doi = "10.3390/pharmaceutics11070335",
language = "English (US)",
volume = "11",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "7",

}

TY - JOUR

T1 - 17-α hydroxyprogesterone nanoemulsifying preconcentrate-loaded vaginal tablet

T2 - A novel non-invasive approach for the prevention of preterm birth

AU - Patki, Manali

AU - Giusto, Kiersten

AU - Gorasiya, Samir

AU - Reznik, Sandra E.

AU - Patel, Ketan

PY - 2019/7

Y1 - 2019/7

N2 - Preterm birth (PTB) is a major cause of infant mortality in the United States and around the globe. Makena®—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.

AB - Preterm birth (PTB) is a major cause of infant mortality in the United States and around the globe. Makena®—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.

KW - 17-α hydroxyprogesterone caproate

KW - Nanoparticle

KW - Preterm birth

KW - Preterm labor

KW - Self-nanoemulsifying system

KW - Vaginal delivery

KW - Vaginal tablet

UR - http://www.scopus.com/inward/record.url?scp=85070196433&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070196433&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics11070335

DO - 10.3390/pharmaceutics11070335

M3 - Article

AN - SCOPUS:85070196433

VL - 11

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 7

M1 - 335

ER -