Swelling-controlled release system for the vaginal delivery of miconazole (original) (raw)
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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.
Aim of present research work was to develop polycarbophil based mucoadhesive vaginal gel comprising of novel combination of Miconazole nitrate (MIZ) & Metronidazole (MNZ) for the treatment of vaginitis. FT-IR studies revealed no interactions. Gel formulations were characterized for pH, spreadability, viscosity, rheological properties, mucoadhesive force, drug content, in vitro drug release study, drug release kinetics studies & antimicrobial efficacy studies. The pH & spreadability was found to be 4.19 & 5.5 to 8.1 cm, which is compatible with vaginal pH & indicates easy spreadability. F5 & F8 were selected as the best formulations with optimum gel viscosity of 22480 & 24800 cps respectively. The detachment stress of the optimized batch was found to be 81.06 & 88.11 respectively. Drug release was non-diffusion controlled. Microbiological studies revealed faster release of drugs than the commercial markets product of Metronidazole & Miconazole nitrate, expressed as inhibition zone. The stability study as per ICH guidelines revealed that the optimized batch holds promise for a high stability. It can be concluded that formulation batch F5 & F8 was considered optimized since it showed better release pattern of both drugs along with other parameters such as viscosity & mucoadhesive properties.
IN VITRO RELEASE AND PREDICTED IN VIVO BEHAVIOR OF METRONIDAZOLE VAGINAL FORMULATIONS
International Journal of Applied Pharmaceutics, 2023
Objective: To document the in vitro release and to predict the in vivo behavior of metronidazole ovules (reference and generic formulations) using USP Apparatus 1 and 4. Prediction of metronidazole plasma concentrations was proposed with the Inverse Release Function approach. The information generated can be considered for the development of new metronidazole vaginal drug products. Methods: Dissolution profiles were obtained using USP Apparatus 1 at 100 rpm and 900 ml of pH 4.5 acetate buffer. Additionally, USP Apparatus 4 at 16 ml/min was used. Drug was quantified at 278 nm every 10 min until 60 min. Mean dissolution time (MDT) and dissolution efficiency (DE) were calculated. Mathematical models such as Korsmeyer-Peppas, Makoid-Banakar, Peppas-Sahlin, Logistic and Weibull were used to fit in vitro data. Percent of prediction error (%PE) for Cmax and AUC0-inf were calculated. Results: Metronidazole ovules of reference formulation released<2% at 60 min in both dissolution methods. Generic formulation released>85%. Values of DE and MDT using USP Apparatus 1 and 4 were 40.40%, 31.94 min, 70.91% and 15.44 min, respectively. In vitro release of generic drug product was better described by Weibull function. %PE for Cmax and AUC0-inf were <15%. Conclusion: Due to limited drug release of reference formulation it was not possible to know the in vitro behavior of this drug product. Generic formulation showed a better in vitro performance by being able to characterize the main dissolution parameters DE and MDT and a release kinetics well defined by a mathematical equation.
Bioadhesive Controlled Release Systems of Ornidazole for Vaginal Delivery
Pharmaceutical Development and Technology, 2006
Background and Objectives: Ornidazole is widely used as an antiprotozoal and antiamoebic drug and its onset of action is within 2 h. The major extent of the drug is metabolized in the liver and excreted in the urine and faeces. Hence, the present study of suppository formulation for sustained systemic delivery of ornidazole is significant which could minimize abdominal disturbances and nausea and delayed onset of action particularly after oral administration. Methods: Bioadhesive suppository formulations were prepared for systemic delivery of ornidazole via rectal and vaginal route. Results: The physical drug-excipient-interaction was confirmed by in-silico docking study. The affinity between drug-HPMC and drug-PEG was found to be-2 and-0.9 k cal/mol respectively. In vitro drug release of the suppositories varied depending on the viscosity grade of HPMC used and all have followed mostly diffusion controlled mechanism. The formulation containing HPMC K100 showed the most sustained release of ornidazole in both the dissolution fluid of pH 7.4 and 4.5 (54.53 and 41.89 % respectively after 360 min). Conclusion: In conclusion, present bio adhesive suppositories could be utilized for sustained systemic delivery of ornidazole via rectal and vaginal route. The findings of this work will contribute to the current knowledge and encourage future pre-clinical research.
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.
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.
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.
A New In-Situ Gel Formulation of Itraconazole for Vaginal Administration
Pharmacology Pharmacy, 2012
In this paper, mucoadhesive in-situ gel with poloxamer and hydroxypropylmethylcellulose formulations of itraconazole were prepared for vaginal application. In addition, rheological, mechanical and mucoadhesive properties and syringeability of the formulations were characterized. The mixtures of Poloxamer 407 and 188 with two different types of hydroxypropylmethylcellulose were used as polymers for gel formulations. Flow rheometry studies and oscillatory analysis of each formulation were performed at 20˚C ± 0.1˚C and 37˚C ± 0.1˚C. All formulations exhibited pseudoplastic flow and typical gel-type mechanical spectra (G′ > G″) after the determined frequency value at 37˚C. Texture profile analysis presented that F3 formulation containing 20% poloxamer 407, 10% poloxamer 188 and 0.5% hydroxypropylmethylcellulose appeared to offer more suitable mechanical and mucoadhesive performance. Using different hydroxypropylmethylcellulose type in formulations didn't significantly change syringeability values. The evaluation of the entire candidate formulations indicated that vaginal formulation of itraconazole will be an alternative for the treatment of vaginal candidiasis with suitable textural and rheological properties. Our results showed that the developed formulations were found worthy of further studies.
Formulation of Transdermal Patches of Miconazole Nitrate and Assesment for Drug Release
Adhesive transdermal patches containing Miconazole Nitrate were prepared as an antifungal therapy. Eudragit RS 100 and Eudragit RL 100 were used in combination as matrix polymers. The patches were assessed for release using a model drug as Miconazole Nitrate by diffusion method. Subsequently, the permeation enhancement effect of DMSO and 2-pyrrolidone was studied. The patches have shown significant controlled release property of the model drug which can be used for a prolonged effect of the drug avoiding the first pass deactivation of Miconazole Nitrate. The patches were also evaluated using various parameters as weight variation, tensile strength, moisture uptake, moisture loss, drug content and other significant parameters. Selected formulations were subjected for their ex-vivo studies on rodent skin.