Formulation and evaluation of metronidazole acid gel for vaginal contraception (original) (raw)
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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.
Efficacy and tolerance of metronidazole and miconazole nitrate in treatment of vaginitis
International Journal of Gynecology & Obstetrics, 2008
Objective: To evaluate the efficacy and tolerability of a vaginal pessary containing 750 mg of metronidazole and 200 mg of miconazole nitrate used daily for 7 days in the treatment of vaginitis. Methods: Ninety-two women with vaginitis participated in this phase 3 study using one vaginal pessary daily for 7 days. Gynecological and microbiological evaluations were carried out prior to and following treatment. Results: Reductions occurred in symptoms and signs of vaginitis. Clinical cure rate was 87.7%, while the cure rates according to microscopy and Candida albicans culture were 81.8% and 73.9%, respectively. The cure rate for bacterial vaginosis was 75% and culture of Gardnerella vaginalis turned negative in 63.6% of cases following treatment. The medication was well tolerated. Conclusion: Use of a combination of 750 mg of metronidazole and 200 mg of miconazole in a single daily application was found to be effective in the treatment of the most common causes of vaginitis.
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.
Contraception, 2006
Background: ACIDFORM is a microbicidal and contraceptive candidate with strong buffering capacity. Methods: This was a Phase I blinded, randomized and crossover clinical study on two products, ACIDFORM and a commercial nonoxynol-9 (N-9) product (2%), evaluating their vaginal safety in 20 couples aged between 19 and 45 years. The women had regular menses, underwent previous tubal ligation, were not breast-feeding, had no vaginal sign and symptom and were in a stable partnership; both partners had no previous STI. Colposcopy, vaginal microbiology, inflammation markers and subject complaints were studied after coitus. Women were randomly assigned sequentially to receive ACIDFORM 0 -30 min (0 -30 min before intercourse), ACIDFORM 8 -10 h (8 -10 h before intercourse) or N-9 0-30 min after a control cycle. Results: Mild/moderate vulvar irritation was observed in five postcoital test colposcopies, burning and pruritus were reported in six treated cycles and non-irritation-related symptoms were found in five cycles with different treatments. No difference in vaginal pH, Nugent scores, H 2 O 2 -producing lactobacillus or leukocytes and interleukin 6 in the cervicovaginal lavage was found between the treatment and control cycles.
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.
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.
Safety Study of Three Concentrations of UniPron Vaginal Contraceptive Microbicidal Gel
American Journal of Biomedical Research, 2018
Background: UniPron is an antimicrobial and a spermicidal agent that contains citric acid as the active component. This study was designed to evaluate the effects of three different concentrations of UniPron in the baboon (Papio anubis) model. Methods: Twenty sexually mature female baboons were used in this study. Vaginal pH and microflora, blood chemistry, vaginal and cervical histology were evaluated at baseline and after administration of 15 ml of UniPron 0.4, 0.8 and 1.2 gm or placebo twice a week for eight weeks to each randomized treatment group. Results: Baseline vaginal pH was 5.2±0.8. There was no significant difference in the vaginal pH and blood chemistry parameters. The microflora composition was diverse and slight variation in percentage frequency between UniPron concentrations was observed. No detectable histological changes were observed in the vaginal or cervical sections. Conclusion: Repeated application of 15 ml of three UniPron concentrations appeared to be safe when administered intravaginally in the baboon model.
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.