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Estradiol–progesterone interaction during the preparation of vaginal rings

Authors

  • Saleh I. Saleh,

    Corresponding author
    1. The Population Council, CBR, 1230 York Avenue, New York, NY 10021
    Current affiliation:
    1. Department of Industrial Pharmacy, College of Pharmacy, Assiut University, Assiut, Egypt.
    • The Population Council, CBR, 1230 York Avenue, New York, NY 10021. Telephone: (966)1 4677372; Fax: (966)1 4676295
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  • Sayed H. Khidr,

    1. Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt
    Current affiliation:
    1. T3A Pharma Group, Abnoub Industrial Zone, P.O. Box 76, Assiut, Egypt.
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  • Sayed M. Ahmed,

    1. Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt
    Current affiliation:
    1. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
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  • Theodore M. Jackanicz,

    1. The Population Council, CBR, 1230 York Avenue, New York, NY 10021
    Current affiliation:
    1. 3802 N. Kenneth Avenue, Chicago, IL 60641.
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  • Harold A. Nash

    1. The Population Council, CBR, 1230 York Avenue, New York, NY 10021
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Abstract

An unexpected enhanced release, in vitro, of estradiol (E2) was observed on the preparation of vaginal rings containing E2 and progesterone (P) in a silicone elastomer. The present work deals with exploring the reason(s) behind this enhanced E2 release. The effect of the ring design (i.e., putting P and E2 in the same compartment or in adjacent or separate compartments) was studied. The effects of the curing temperature as well as the curing time were also investigated. The possible interaction(s) between P and E2 on simple heating of their mixtures was investigated using infrared (IR), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR) techniques. Also, the dissolution behavior of P, E2, and their mixture before and after heating was studied. The ring design, with respect to the position of the steroid layer(s), affected the release of P and E2 from the vaginal rings. Curing the rings at higher temperatures (≥140°C) for ≥30 min resulted in an enhanced release of the steroids, especially E2. The IR, DSC, phase diagram, and NMR results indicate that an interaction between P and E2, leading to the formation of a molecular complex, took place. It was concluded that putting P and E2 in the same compartment and curing by heating at a high temperature and for an extended time promoted this kind of interaction. The greater hydrophobicity of the interaction product, relative to that of E2, was considered the main reason behind the enhanced in vitro release of E2 from the vaginal rings. © 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:258–265, 2003

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