Screening of mucoadhesive vaginal gel formulations

Rational design of vaginal drug delivery formulations requires special attention to vehicle properties that optimize vaginal coating and retention. The aim of the present work was to perform a screening of mucoadhesive vaginal gels formulated with carbomer or carrageenan in binary combination with a second polymer (carbomer, guar or xanthan gum). The gels were characterised using in vitro adhesion, spreadability and leakage potential studies, as well as rheological measurements (stress and frequency sweep tests) and the effect of dilution with simulated vaginal fluid (SVF) on spreadability. Results were analysed using analysis of variance and multiple factor analysis. The combination of polymers enhanced adhesion of both primary gelling agents, carbomer and carrageenan. From the rheological point of view all formulations presented a similar behaviour, prevalently elastic and characterised by loss tangent values well below 1. No correlation between rheological and adhesion behaviour was found. Carbomer and carrageenan gels containing the highest percentage of xanthan gum displayed good in vitro mucoadhesion and spreadability, minimal leakage potential and high resistance to dilution. The positive results obtained with carrageenan-xanthan gum-based gels can encourage the use of natural biocompatible adjuvants in the composition of vaginal products, a formulation field that is currently under the synthetic domain.

O planejamento racional de formulações para a liberação vaginal de fármacos requer atenção especial às propriedades do veículo, que otimizem o revestimento e a retenção vaginal. O objetivo do presente trabalho foi realizar uma triagem de géis vaginais mucoadesivos formulados com carbomero ou carragenina em combinação binária com um segundo polímero (carbomero, goma guár ou xantana). Os géis foram caracterizados usando estudos in vitro de aderência, espalhabilidade e potencial de vazamento, bem como medições reológicas (testes de varredura de tensão e frequência) e o efeito de diluição com fluido vaginal simulado (SVF) na espalhabilidade. Os resultados foram analisados utilizando a análise de variância e de fator múltiplo. A combinação de polímeros reforçou a adesão de ambos os agentes gelificantes primários, carbomero e carragenina. Do ponto de vista reológico todas as formulações apresentaram comportamento semelhante, predominantemente elástico e caracterizado por valores de tangente de perda bem abaixo de 1. Não se encontrou correlação entre as medições reológicas e o comportamento de adesão. Os géis de carbomero e carragenina contendo o maior porcentual de goma xantana apresentaram melhor mucoadesão e espalhabilidade, menor potencial de vazamento e maior resistência à diluição in vitro. Os resultados positivos obtidos com géis de carragenina-goma xantana podem incentivar o uso de adjuvantes biocompatíveis naturais na composição dos produtos vaginais, um campo de formulação atualmente sob o domínio de produtos sintéticos.

In vivo optical imaging of human vaginal gel thickness distributions with a probe-based, dual-modality instrument.

ABSTRACT. We used a probe-based dual-modality optical imaging instrument to measure in vivo coating thickness distributions of a gel distributed along the vaginal lumen, in a clinical study. The gel was a surrogate for one delivering an anti-HIV topical microbicide. Imaging data from Fourier-domain multiplexed low-coherence interferometry (mLCI) and fluorimetric measurements were compared to assess the feasibility and accuracy of mLCI in measuring in vivo gel coating thickness distributions. In each study session, 3.5 mL of Replens gel was inserted to the vaginal fornix while the participant was supine. The participant either: 1. remained supine (10 or 60 min); or 2. sat up (1 min), stood up (1 min), sat down (1 min) and returned to the supine position; net elapsed time was 10 or 60 min after which the gel distribution was imaged. Local coating thickness distributions were qualitatively and quantitatively similar. Here mLCI did not accurately measure thicker gel coatings (>0.8 mm), a limitation not seen with fluorimetry. However, mLCI is capable of measuring in vivo microbicide gel distributions with resolution on the order of 10 µm, without the need for exogenous contrast agents, and can accurately capture relevant summary coating measures in good agreement with fluorimetry.

Advances in development, scale-up and manufacturing of microbicide gels, films, and tablets.

Vaginal HIV microbicides are topical, self administered products designed to prevent or significantly reduce transmission of HIV infection in women. The earliest microbicide candidates developed have been formulated as coitally dependent (used around the time of sex) gels and creams. All microbicide candidates tested in Phase III clinical trials, so far, have been gel products with non-specific mechanisms of action. However, recently, research is focusing on compounds containing highly potent and specific anti-retrovirals. These specific anti-retrovirals are being formulated as primary dosage forms such as vaginal gels or in alternative dosage forms such as fast dissolve films and tablets. Recent innovations also include development of combination products of highly active antiviral drugs such as reverse transcriptase inhibitors and entry inhibitors, which would theoretically be more effective and would reduce the possibility of drug resistance. In this article, an overview of recent advances in the microbicide gel, film, and tablet formulations and issues pertaining to scale-up, formulation, and evaluation challenges and regulatory guidelines have been presented. This article forms part of a special supplement covering presentations on gels, tablets, and films from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA.

Vaginal gel adsorption and retention by human vaginal cells: visual analysis by means of inorganic and organic markers.

To improve efficiency and prolong protection, modern gynecological preparations frequently incorporate polymeric molecules that add a certain degree of viscosity in order to increase adhesion with vaginal cells and prolong local delivery of active molecules. The aim of this study was to investigate the possibility of visualising the ability of a commercial medicated gynecological gel to bind to and be retained by human vaginal cells. The gel formulation included the essential oils of Thymus vulgaris and Eugenia cariophylla, which contain active molecules such as thymol and eugenol that are known to have useful antibacterial and antimycotic activities. The adherence of different dilutions of the gel to human vaginal cells was visualised by means of Nomarski interference contrast microscopy and scanning electron microscopy using ferric oxide particles and Escherichia coli as inorganic and organic markers, both of which made it possible to visualise the binding of the thin transparent layer of gel and the retaining effect, which was proportional to the degree of dilution.

Analise do terconazol em formulacoes farmaceuticas por cromatografia liquida de alta eficiencia (CLAE) / Analysis terconazole in pharmaceutical formulations by liquid chromatography (HPLC)

Cromatografia liquida de alta eficiencia e utilizada para identificacao do terconazol na materia prima e determibacao quantitativa deste farmaco nas especialidades farmaceuticas de creme e ovulo. A analise do terconazol por CLAE apresenta resultados que comprovam a exatidao e precisao do metodo proposto. os resultados de recuperacao analisados, com valor medio de 99,33 por cento e 99,89 por cento para as especialidades farmaceuticas ovulos e creme, respectivamente, nos permitem indicar a cromatografia liquida de alta eficiencia como metodo ideal para determinacao do terconazol nas formas farmaceuticas comercializadas no Brasil

Analysis of conjugated estrogens in a vaginal cream formulation by capillary gas chromatography.

A capillary gas-chromatographic method is described for the quantitative analysis of nine equine estrogens in a vaginal cream formulation. The sodium sulfate ethers of the estrogens were selectively extracted from the formulation, subjected to enzyme hydrolysis, and derivatized to their oxime-trimethylsilyl esters. Resolution of the resulting derivatives was achieved on short (15 m) capillary column, wall-coated with cyanopropylmethyl silicon stationary phase.