Formulation and evaluation of mucoadhesive vaginal gel containing novel combination of metronidazole and miconazole nitrate for the treatment of vaginitis (original) (raw)
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A B S T R A C T Vaginitis is a common infection caused by bacteria and fungi leading to inflammation, itching and redness in the vaginal mucosal region, which can be treated by antibacterial and antifungal drug therapy. The current work is focused on development of aerosol foam formulation of an in situ gel for treatment of vaginitis. For this purpose, in situ gel formulations were prepared using carbopol 940, carrageenan and cellulose polymers at different composition and converted to foam spray using sodium lauryl sulphate as foaming agent. The prepared formulations were evaluated for standard quality parameters and the results confirmed the significance of the optimized formulation to deliver the drug in vaginal region and provide sustained release for 8 h. Based on the results obtained, it was evident that the in situ gel formulations comprising of 0.45% of carbopol 940 with 0.35% HPMC K4M and the 0.35% of carbopol 940 with 0.35% HPC were optimum for gelation process. These formulations also released less than 50% of drug in simulated vaginal fluid at the end of 8 h. In conclusion, optimization of polymer concentration for the in vivo gelation process would be the efficient way to develop stable vaginal drug delivery systems.
Formulation and Evaluation of Metronidazole Microspheres-Loaded Bioadhesive Vaginal Gel
Asian Journal of Pharmaceutical and Clinical Research, 2017
ABSTRACTObjectives: The objective of the present work is to develop and characterize metronidazole microsphere-loaded bioadhesive vaginal gel to ensurelonger residence time at the infection site, providing a favorable release profile for the drug.Methods: Microsphere was prepared by solvent evaporation method in various ratios of metronidazole to poly-ε-caprolactone (PCL). Physicochemicalevaluation of microspheres includes determination of solubility in simulated vaginal fluid, partition coefficient (n-octanol/citrate phosphatebuffer pH 4.5), particle size distribution, entrapment efficiency, X-ray diffraction, and surface morphology by scanning electron microscopy (SEM).Drug excipient compatibility was established by Fourier transform infrared and differential scanning calorimetry studies. Bioadhesive gel wasprepared using Carbopol 934P and HPMC K4M in various concentrations, and methyl paraben was used as a preservative. The pH was adjustedwith triethanolamine which resulted in a ...
METRONIDAZOLE BIOADHESIVE VAGINAL SUPPOSITORIES: FORMULATION, IN VITRO AND IN VIVO EVALUATION
Drug administration via mucosal membranes, including the vaginal, has the advantage of by passing the hepatogastrointestinal first pass metabolism associated with oral administration. Metronidazole suppositories were prepared using different suppository bases viz., water soluble bases (PEGs and gelatin) emulsion and fatty bases. The physicochemical properties of most of the prepared MTZ suppositories comply with the pharmacopoeial limits and passed the quality control tests. In general, water soluble suppository bases gave higher release than did the emulsion in citrate buffer pH 4. PEG base (F14), gelatin base (Fl8) and emulsion base (F23) gave the highest drug release and selected for further investigation. The release of MTZ from polyethylene glycol bases followed, first and Higuchi order release model, while gelatin and emulsion obeyed first model. The tested suppository showed enhancement of drug absorption from tested suppository and the One way ANOVA analysis for AUC(0-∞) showed that the P value is 0.0502, considered not significant. The microbiological results showed that the bioadhesive formulae that released the concentration of 0.25 mg/ml of the drug and sustained this concentration for 120 min can be effective on C. albicans moreover bioavailability study was performed on flagyl ® vaginal suppository (market product) and the prepared pluronic127 –cp934 bioadhesive vaginal gel ,eight female rabbits were randomly divided into two groups, each containing four rabbits the results showed that the tested formulae did not exhibit enhancement in bioavailability in comparison to the market product which mean lower side effects and localized effect inside the vagina.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2018
The use of conventional vaginal formulations of miconazole nitrate (MN) in the treatment of deep-seated VVC (vulvovaginal candidiasis) is limited by poor penetration capacity and low solubility of MN, short residence time and irritation at the application site. Surface-modified mucoadhesive microgels were developed to minimize local irritation, enhance penetration capacity and solubility and prolong localized vaginal delivery of MN for effective treatment of deep-seated VVC. Solid lipid microparticles (SLMs) were prepared from matrices consisting of hydrogenated palm oil (Softisan® 154, SF) and super-refined sunseed oil (SO) with or without polyethylene glycol (PEG)-4000, characterized for physicochemical performance and used to prepare mucoadhesive microgels (MMs) encapsulating MN, employing Polycarbophil as bioadhesive polymer. The MMs were evaluated for physicochemical performance and in vitro drug release in simulated vaginal fluid (pH=4.2), whereas mucoadhesive, rheological and...
Iranian Journal of Pharmaceutical Sciences
Hydrogel-Based Metronidazole Bioadhesive Tablet (HMBT) was prepared as a novel vaginal delivery system to achieve Controlled release of drug from the tablet for vaginal candidiasis. The highly swollen hydrogel were prepared by dissolving chitosan in acetic acid solution containing drug, followed by neutralisation with sodium hydroxide and characterized by SEM, DSC and FT-IR and evaluated for % swelling. The drug loaded hydrogels were incorporated into tablet formulation by dry granulation method using bioadhesive polymers such as HPMC, sodium CMC and guar gum in different ratios. HMBT was tested for drug content, hardness, friability, weight variation, thickness, swelling studies, in vitro drug release, bioadhesive strength, in vivo studies and antifungal activity. The FT-IR and DSC spectra's revealed that there was no chemical interaction between drug and polymers used. SEM revealed that particles of hydrogels appeared small and irregular shaped with large numbers of pores. F3 formulation shows good in vitro release profile with highest bioadhesive strength. From the in vivo study in rabbit it was found that the HMBT hold the tablet for more than 12 hours inside the vaginal tube. It may be concluded from present study that HMBT can be used as a novel delivery system for local therapy of vaginal candidiasis which can controlled the release of drug for prolong period of time.
Design and Evaluation Of Metronidazole Vaginal Tablet For Once Daily Administration
International Journal of ChemTech Research
In this study bioadhesive sustained release tablets of metronidazole for once daily administration were formulated. This formulation helps to increase the localized effect of metronidazole by formulating the vaginal bioadhesive tablet and to increase the ease of application when compared to various types of vaginal gels and creams that are available in the market.Metronidazole is a nitro imidazole derivative class of anti-protozoal drug used to treat amoebiasis, vaginitis, trichomonal infections, trepenomal infections and giardisis. The objective of the present study is to formulate the bioadhesive controlled release drug delivery system which would remain in contact with the vaginal tissue for prolonged period of time in view to maximize the bioavailability and therapeutic efficacy of the drug.Bioadhesive tablets were prepared using metronidazole and sodium alginate in different proportions by wet granulation method. The prepared tablets were evaluated for weight variation, hardness, friability, dissolution and swelling studies.The release of drug from various vaginal bioadhesive tablets exhibited the following order F4>F1>F3, but F2 exhibited faster drug release compared to other formulations, which is not a desired characteristic for the treatment of vaginosis. By observing the above results, more ca +2 ions became available to bind with sodium alginate during the wet granulation stage of the preparation. As a result better and stronger gel was formed when high amount of calcium carbonate was used. As the concentration of ca +2 ions increases, stronger gel of calcium alginate is formed that delay the influx of the dissolution medium and efflux of the dissolved drug out the matrix. As a result drug is released in amore sustained manner.
Formulation and In Vitro Evaluation of In Situ Gels Containing Secnidazole for Vaginitis
Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan, 2009
Gel dosage forms are successfully used as drug delivery systems considering their ability to prolong the drug release. The main objective is to formulate and evaluate in situ vaginal gels of secnidazole, based on ion activated systems. The system utilizes polymers that exhibit sol-to-gel phase transition due to change in speciˆc physico chemical parameters. Ion triggered system using gellan gum (0.1 0.75％ w/v) along with sodium carboxymethylcelluose was used to prolong the release of secnidazole (1％ w/v). Formulations were evaluated for gelling capacity, viscosity, gel strength, mucoadhesive force, spreadability, microbiological studies and in vitro release studies. The transformation of sols occur in the presence of monovalent/divalent cations in the dissolution medium. EŠect of calcium carbonate and other process parameters were optimized and found that increase in calcium ions produce stronger gels. The drug content, clarity, and pH of formulation were found to be satisfactory. The viscosity was found to be in the range of 0.005 to 0.085 for sols, whereas for the gels 16 Pa･s. Formulation showed pseudoplastic ‰ow with thixotrophy. The gel strength (using texture analyzer) and mucoadhesion was found to be up to 6.5 g and 4 g respectively. The optimized formulations were able to release the drug for 360 min. The gels are expected to improve the administration at the site of infection and decrease frequency.
FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration
International Journal of Pharmaceutics, 2009
Topical administration of the antibacterial metronidazole (MET) represents the most common therapy in the treatment of bacterial vaginosis (BV). The formulations generally available for BV therapy are creams, gels, vaginal lavages and vaginal suppositories. In this study, a new dosage form, containing MET, was developed with the aim to realize vaginal mucoadhesive tablets by including bioadhesive polymers as chitosan (FG90C), polyvinylpyrrolidone (PVPK90) and polycarbophil (PCPAA1), blended in different ratios. All formulations were characterized by studies of DSC, friability, hardness, hydration, mucoadhesion, in vitro release and antibacterial activity.
Journal of Biomaterials Applications, 2014
Microporous, poly (e-caprolactone) (PCL) matrices loaded with the antibacterial, metronidazole were produced by rapidly cooling suspensions of drug powder in PCL solutions in acetone. Drug incorporation in the matrices increased from 2.0% to 10.6% w/w on raising the drug loading of the PCL solution from 5% to 20% w/w measured with respect to the PCL content. Drug loading efficiencies of 40-53% were obtained. Rapid 'burst release' of 35-55% of the metronidazole content was recorded over 24 h when matrices were immersed in simulated vaginal fluid (SVF), due to the presence of large amounts of drug on matrix surface as revealed by Raman microscopy. Gradual release of around 80% of the drug content occurred over the following 12 days. Metronidazole released from PCL matrices in SVF retained antimicrobial activity against Gardnerella vaginalis in vitro at levels up to 97% compared to the free drug. Basic modelling predicted that the concentrations of metronidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration of metronidazole against G. vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of metronidazole in the treatment and prevention of bacterial vaginosis.