Bioadhesive mini-tablets for vaginal drug delivery.

Marianne Hiorth,Susanne Nilsen,Ingunn Tho

doi:10.3390/pharmaceutics6030494

Marianne Hiorth, Susanne Nilsen + Show 1 more

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https://doi.org/10.3390/pharmaceutics6030494

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Abstract

Different non-ionic cellulose ethers (methyl cellulose, MC; hydroxyethyl cellulose, HEC; hydroxypropyl cellulose, HPC; hydroxypropylmethyl cellulose, HPMC) and microcrystalline cellulose (MCC) were investigated as matrix formers for preparation of mini-tablets targeting vaginal drug delivery. Hexyl aminolevulinat hydrochloridum (HAL) was used as a model drug. The mini-tablets were characterized with respect to their mechanical strength, bioadhesion towards cow vaginal tissue in two independent tests (rotating cylinder test, detachment test using texture analyzer), and dissolution rate in two media mimicking the pH levels of fertile, healthy and post-menopausal women (vaginal fluid simulant pH 4.5, phosphate buffer pH 6.8). Mini-tablets with a matrix of either HPMC or HPC were found to possess adequate mechanical strength, superior bioadhesive behavior towards vaginal tissue, and pH independent controlled release of the model drug, suggesting that both systems would be suited for the treatment of women regardless of age, i.e., respective of their vaginal pH levels. Bioadhesive mini-tablets offer a potential for improved residence time in the vaginal cavity targeting contact with mucosal tissue and prolonged release of the drug.

Highlights

The vagina is an important application site for drug delivery, especially for local therapy of different diseases, such as bacterial, fungal and protozoa infections, for HIV prevention, delivery of contraceptives, spermicides or labor-inducers and for the treatment of precancerous lesions [1,2].It may serve an alternative route for systemic drug delivery [3]. the vaginal tissue is referred to as mucosal, the vagina does not have secretory glands.a mixture of fluids originating from a number of different sources comprises a moist film coating the vaginal surface
The composition, volume, pH and viscosity of the vaginal fluids are affected by age, cyclic hormone changes, and sexual activity; factors that may influence the effect of vaginally applied drug delivery systems or dosage forms
The filling volume was kept constant for all formulations; since the polymers have different density, the mass of the mini-tablets varied between the formulations, with microcrystalline cellulose (MCC) producing the heaviest and Hydroxypropyl cellulose (HPC) the least heavy units

Summary

Introduction

The vagina is an important application site for drug delivery, especially for local therapy of different diseases, such as bacterial, fungal and protozoa infections, for HIV prevention, delivery of contraceptives, spermicides or labor-inducers and for the treatment of precancerous lesions [1,2].It may serve an alternative route for systemic drug delivery [3]. the vaginal tissue is referred to as mucosal, the vagina does not have secretory glands.a mixture of fluids originating from a number of different sources comprises a moist film coating the vaginal surface. The vagina is an important application site for drug delivery, especially for local therapy of different diseases, such as bacterial, fungal and protozoa infections, for HIV prevention, delivery of contraceptives, spermicides or labor-inducers and for the treatment of precancerous lesions [1,2]. It may serve an alternative route for systemic drug delivery [3]. The composition, volume, pH and viscosity of the vaginal fluids are affected by age, cyclic hormone changes, and sexual activity; factors that may influence the effect of vaginally applied drug delivery systems or dosage forms. Changes due to infections or pregnancy may lead to different activity of drugs [3]

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