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Design of a Semisolid Vaginal Microbicide Gel by Relating Composition to Properties and Performance

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ABSTRACT

Purpose

Develop a preclinical in vitro algorithm enabling de novo design of semisolid vaginal drug delivery gels, by using biomechanical modeling of gel spreading in the vaginal canal and empirically relating gel composition to mechanical properties and predicted performance.

Methods

Gel performance was defined through a multivariate objective function constructed from gels’ mechanical properties and selected performance criteria for gel spreading within the vaginal canal. Mixture design of experiment was used to establish a semi-empirical relationship linking composition-property and property-performance relationships for gels with varying concentrations of hydroxyethylcellulose and Carbopol 974P. This permits definition of a local optimum for gel composition and volume of administration, within a defined gel composition space.

Results

Rheological behavior and, consequently, the value of the objective function varied broadly with composition. The algorithm indicated a 3.0 wt% HEC gel as the near optimal composition for a 3.5 mL applied volume for gels designed to spread throughout the vagina.

Conclusions

The algorithm introduced herein is a novel tool that facilitates an understanding of the composition-property-performance relationship for vaginal semisolid drug delivery gels. This approach has promise as a scientific methodology for evaluation and optimization of vaginal gels prior to in vivo investigations.

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Abbreviations

A:

vaginal area coated by the gel

A* :

value of A at which the score becomes zero

Amax :

area of the vaginal canal

API:

active Pharmaceutical Ingredient

CPPR:

composition-property-performance relationship

HEC:

Hydroxyethylcellulose

MDOE:

mixture design of experiment

RSM:

response surface modeling

S:

score

Scombined :

average of Sundiluted and Sdiluted

Sdiluted :

score for gels diluted 1:4 with VFS

Sundiluted :

score for undiluted gels

TFV:

Tenofovir

V:

volume of the gel

VFS:

vaginal fluid simulant

VL :

volume of the gel leaked

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ACKNOWLEDGMENTS

This work was generously supported by CONRAD under a Cooperative Agreement with USAID (HRN-A-00-98-00020-00). The views expressed by the authors do not necessarily reflect those of USAID.

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Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112-5820, USA

    Alamelu Mahalingam & Patrick F. Kiser

  2. Department of Bioengineering, University of Utah, Salt Lake City, UT, 84112-5820, USA

    Eric Smith, Judit Fabian, Festo R. Damian & Patrick F. Kiser

  3. Department of Biomedical Engineering, Duke University, Durham, NC, 27708-0281, USA

    Jennifer J. Peters & David F. Katz

  4. CONRAD, 1911 North Fort Myer Drive, Suite 900, Arlington, VA, 22209, USA

    Meredith R. Clark & David R. Friend

  5. Department of Bioengineering, University of Utah, 20 S. 2030 E., Rm. 108, Salt Lake City, UT, 84112-9458, USA

    Patrick F. Kiser

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  1. Alamelu Mahalingam
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  3. Judit Fabian
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Correspondence to Patrick F. Kiser.

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Mahalingam, A., Smith, E., Fabian, J. et al. Design of a Semisolid Vaginal Microbicide Gel by Relating Composition to Properties and Performance. Pharm Res 27, 2478–2491 (2010). https://doi.org/10.1007/s11095-010-0244-1

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  • DOI: https://doi.org/10.1007/s11095-010-0244-1

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