Esra Baloğlu

Strategies to Prolong the Intravaginal Residence Time of Drug Delivery Systems

The vagina has been studied as a favorable site for local and systemic delivery of drugs for female-related conditions. There are a large number of vaginal medications on the market and most of them require frequent application due to their short vaginal residence time. A prolonged vaginal residence time of formulations is therefore a key parameter for improved therapeutic efficacy. Promising approaches to prolong the residence time base on mucoadhesion, in- situ sol-gel transition and mechanical fixation. Mucoadhesive drug delivery systems can be tailored to adhere to the vaginal tissue. In-situ gelling systems offer the advantage of increased viscosity in vaginal cavity and consequently reduce outflow from the vagina. Mechanical fixation needs specially shaped drug delivery systems and reduce the frequency of administration significantly. Within this review an overview on these different strategies and systems is provided. Furthermore, the techniques to evaluate the potential of these systems for prolonged vaginal residence time are described.

Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base

This study described the thermosensitive formulations composed of poloxamer mixtures for use as drug delivery platform via mucosal route. It also characterized the poloxamer mixtures’ rheological, mechanical and mucoadhesive properties. Poloxamer (Plx) 407 and Plx 188 were used alone and together for preparing the mucosal drug delivery platform. The mixtures of Plx 407 and Plx 188 in ratio of 15:15 (F5); 15:20 (F6); 20:10 (F7) existed liquid at room temperature, but gelled at physiological temperature. Flow rheometry studies and oscillatory analysis of each formulation were performed at 20 ± 0.1°C and 37 ± 0.1°C. F5 and F7 formulations exhibited typical gel-type mechanical spectra (G′ > G″) after the determined frequency value at 37°C whereas F6 behaved as weakly cross-linked gel. Texture profile analysis presented that F5 and F7 showed similar mechanical properties and can be used as base for mucosal dosage form. Mucoadhesion studies indicated the difference among the formulations and the effect of the mucosal surface on mucoadhesive properties. Mucin disc, bovine vaginal and buccal mucosa were used as mucosal platform for mucoadhesion studies. It is suggested that these investigations may be usefully combined to provide a more rational basis for selecting the ratio of Plx to prepare a topical thermosensitive drug delivery system for mucosal administration.

An in vitro investigation for vaginal bioadhesive formulations: bioadhesive properties and swelling states of polymer mixtures.

Bioadhesive tablet formulations have been developed for mucosal application. Sixteen different bioadhesive tablet formulations were prepared and evaluated. Their bioadhesion to vaginal mucosa were studied by tensile testing method. The swelling behaviour of the tablets in three different solutions was also investigated. In addition, the effect of the formulations on pH of the medium was followed. The most favorable formulation resulted a mixture of Carbopol 934 and Pectin (2:1). The highest bioadhesive strength, the highest swelling volume and the lowest pH reduction were obtained with this formulation.

In-situ gel formulations of econazole nitrate: preparation and in-vitro and in-vivo evaluation

Objectives  This study describes the in‐situ gelling of econazole nitrate containing thermosensitive polymers composed of poloxamer 407 and 188 as a novel treatment platform for vaginal candidiasis.

The efficacy of three desensitizing agents in treatment of dentine hypersensitivity

Purpose:  The purpose of this study was to evaluate the efficacy of three desensitizing agents vs. placebo.

Bioadhesive Controlled Release Systems of Ornidazole for Vaginal Delivery

Our objective was to develop a bioadhesive vaginal tablet formulation of ornidazole by using different polymer mixtures, to evaluate the bioadhesive tablet properties, and to investigate the irritation potential of the formulations to the rat vaginal tissue. Vaginal tablets of ornidazole were directly compressed with bioadhesive and swellable polymer mixtures as release-controlled agents. Carbopol 934 (Cp), pectin (Pc), hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (Na CMC), and guar gum (GG) were used in different ratios. Bioadhesive properties, swelling capacity, release studies, and histological studies of the formulations were carried out. The bioadhesive strength between bovine vagina and surface of the tablets was determined by tensile experiments, and it was found to be dependent on Cp content. The release mechanism was described and found to be non-Fickian for all formulations. Dissolution data were evaluated statistically. No histological damage was found except one formulation containing high amount of guar gum.

Evaluation of chitosan based vaginal bioadhesive gel formulations for antifungal drugs

Abstract The aim of the present study was to evaluate chitosan as a vaginal mucoadhesive gel base for econazole nitrate and miconazole nitrate. To this aim, different types of chitosan with different molecular masses and viscosity properties [low molecular mass chitosan (viscosity: 20,000 mPa s), medium molecular mass chitosan (viscosity: 200,000 mPa s), high molecular mass chitosan (viscosity: 800,000 mPa s)] have been used. First, rheological studies were conducted on chitosan gels. Mechanical, syringeability and mucoadhesive properties of chitosan gels were determined. Release profiles of econazole nitrate and miconazole nitrate from chitosan gels were obtained and evaluated kinetically. In addition, anticandidal activities of formulations were determined. Finally, vaginal retention of chitosan gels in rats was evaluated by in vivo distribution studies. Based on the results, it can be concluded that gels prepared with medium molecular mass chitosan might be effectively used for different antifungal agents in the treatment of vaginal candidiosis, since it has high mucoadhesiveness, suitable mechanical and release properties with good vaginal retention

Mucoadhesive in situ gel formulation for vaginal delivery of clotrimazole: formulation, preparation, and in vitro/in vivo evaluation

Abstract The purpose of this study was to develop a suitable mucoadhesive in situ gel formulation of clotrimazole (CLO) for the treatment of vaginal candidiasis. For this aim, the mixture of poloxamer (PLX) 407 and 188 were used to prepare in situ gels. Hydroxypropyl methylcellulose (HPMC) K100M or E50 was added to in situ gels in 0.5% ratio to improve the mucoadhesive and mechanical properties of formulations and to prolong the residence time in vaginal cavity. After the preparation of mucoadhesive in situ gels; gelation temperature/time, viscosity, mechanical, mucoadhesive, syringeability, spreadibility and rheological properties, in vitro release behavior, and anticandidal activities were determined. Moreover vaginal retention of mucoadhesive in situ gels was investigated with in vivo distribution studies in rats. Based on the obtained results, it was found that gels prepared with 20% PLX 407, 10% PLX 188 and 0.5% HPMC K100M/E50 might be suitable for vaginal administration of CLO. In addition, the results of in vivo distribution studies showed that gel formulations remained on the vaginal mucosa even 24 h after application. In conclusion, the mucoadhesive in situ gels of CLO would be alternative candidate for treatment of vaginal candidiasis since it has suitable gel properties with good vaginal retention.

Microencapsulation of Melaleuca alternifolia (Tea Tree) Oil by Using Simple Coacervation Method

Abstract Glutaraldehyde (GA) crosslinked gelatin (G) microcapsules containing tea tree oil (TTO) were prepared by the simple coacervation technique. The effects of variations in concentrations of the G, TTO and GA used during the microencapsulation process, on the oil load of the microcapsules, the oil content, the encapsulation efficiency and the release rate of oil were determined. The size distribution and the morphology of the microcapsules were characterized by optical and scanning electron microscopy. It was determined by FTIR studies that there was no evidence for any significant interaction between G and TTO

The effect of the type and the concentration of the lipophilic surfactant on the stability and release kinetics of the W/O/W multiple emulsions

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