Systems Approach to Vaginal Delivery of Drugs V: In Situ Vaginal Absorption of 1-Alkanoic Acids

Hwang, Shyh‐Lung; Owada, Eiji; Suhardja, L.; Ho, Norman F.H.; Flynn, Gordon L.; Higuchi, William I.

doi:10.1002/jps.2600660609

Cited by 17 publications

(2 citation statements)

References 8 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to pH, other physiological factors may impact the absorption and efficacy of vaginally delivered drugs. Cyclical changes, associates to age, phase of the menstrual cycle, and pregnancy are known to modify the epithelial thickness and composition of vaginal fluids (41)(42)(43)(44)(45)(46)(47). Certainly, barriers to successful drug delivery and targeting such as a changing epithelial barrier, presence of biological fluids at the surface of the tissue, enzymatic activity of vaginal fluid, and hydrogen peroxide as well as other constituents produced by normal microflora have the potential to reduce biological activity of microbicide candidates if not considered during product development (48).…”

Section: Physiology Of the Vagina And Barriers To Drug Deliverymentioning

confidence: 99%

Vaginal Drug Delivery Systems for HIV Prevention

Rohan

Sassi

2009

AAPS J

140

130

View full text Add to dashboard Cite

Abstract. Microbicides have become a principal focus for HIV prevention strategies. The successful design of drug delivery systems for vaginal microbicide drug candidates brings with it a multitude of challenges. It is imperative that the chemical and physical characteristics of the drug candidate and its mechanism of action be clearly understood and considered to successfully deliver and target drug candidates efficiently. In addition, an understanding of the dynamic nature of the vaginal environment, the tissue and innate barriers present, as well as patient preferences are critical considerations in the design of effective microbicide products. Although the majority of drug candidates clinically evaluated to date have been delivered using conventional semisolid aqueous-based gel dosage forms, drug delivery system design has recently been extended to include advanced delivery systems such as vaginal rings, quick-dissolve films, and tablets. Ultimately, it may be necessary to develop multiple dosage platforms for a single active agent to provide users with options that can be used within the constraints of their social environment, personal choice, and environmental conditions.

show abstract

Section: Physiology Of the Vagina And Barriers To Drug Deliverymentioning

confidence: 99%

Vaginal Drug Delivery Systems for HIV Prevention

Rohan

Sassi

2009

AAPS J

140

130

View full text Add to dashboard Cite

show abstract

“…Here, the surface area c,f the vagina was fixed by the use of fib-cage cells designed t'or intravaginal insertion through the vulval orifice and individualized to fit the vaginal dimensions of the monkey. Vaginal permeability studies in the rabbit doe with n-alkanols (Hwang et aL, 1976), n-alkanoic acids (Hwang et al, 1977) and steroids (Flynn et al, 1976) to characterize the membrane and w~th steroid-silicone rubber matrix (Flynn et al, 1976) have been extended to similar studies in the monkey *…”

Section: Introductionmentioning

confidence: 99%

Vaginal drug absorption in the rhesus monkey: Bioavailability method and assessment of estrogens

Park¹,

Langworthy²,

Behl³

et al. 1979

International Journal of Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Novel experimental and theoretical methods in evaluating the systemic bioavailability of estrogens delivered via the vaginal route have been developed. The approaches were demonstrated for estrone and estradiol in the rhesus monkey. These newly developed techniques have made it possible to quantify first pass vaginal membrane metabolism for estrone and for estradiol and to disthlguish this process from peripheral tissue metabolism. This was achieved by obtaining steady-state blood levels of the steroids and all significant metabolites resulting from identical zero-order infusion rates of the steroid by the vaginal and intravenous routes. Comparison of the blood levels gave rapid estimations of bioavailability. The modeling of the steady-state situation and quantification of the kinetic parameters were employed such that differences in blood levels from vaginal and intraven~aus drug infusion mirrored the membrane transport and metabolic events. Membrane metabolism of infused estrone and estradiol reduced the blood levels of these steroids by al~out 55 and 61%, respectively, of that expected in the absence of membrane metabolism. About 45% of vaginally administered estrone appeared directly in the blood, as estrone and 9% as estradiol and 46% as total conjugates. The dominant route of membrane metabolism of estrone was estrone conjugation rather than reduction to estiadiol. When estradiol was infused vaginally, 26% estradiol appeared in the blood and 35% as estrone and 39% as total conjugates; the dominant route of metabolism was the ,~xidation to estrone and not estradiol conjugation. * Manuscripts in preparation on vaginal absorption in rhesus monkey of n-alkanols, n-alkanoic acids, estrogens, progesterone and inplanted steroid-silicone rubber vaginal devices.

show abstract