Design of a semisolid vaginal microbicide gel by relating composition to properties and performance.
OBJECTIVE
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.
Mahalingam
Alamelu
A
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112-5820, USA.
Smith
Eric
E
Fabian
Judit
J
Damian
Festo R
FR
Peters
Jennifer J
JJ
Clark
Meredith R
MR
Friend
David R
DR
Katz
David F
DF
Kiser
Patrick F
PF
D000890:Anti-Infective Agents / Q000008:administration & dosage*; D005260:Female; D005782:Gels; D006801:Humans; D014621:Vagina
D000890:Anti-Infective Agents; D005782:Gels