Evaluation of polycaprolactone matrices for the intravaginal delivery of metronidazole in the treatment of bacterial vaginosis (original) (raw)
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Journal of pharmaceutical sciences, 2017
Poly(ɛ-caprolactone) (PCL) intra-vaginal matrices were produced for local delivery of a combination of antibacterials, by rapidly cooling a mixture of drug powders dispersed in PCL solution. Matrices loaded with different combinations of metronidazole (10, 15 and 20% w/w) and doxycycline (10% w/w), were evaluated in vitro for release behavior and antibacterial activity. Rapid 'burst release' of 8-15% of the doxycycline content and 31-37% of the metronidazole content occurred within 24 h when matrices were immersed in simulated vaginal fluid (SVF) at 37°C. The remaining drug was extracted gradually over 14 days to a maximum of 65-73% for doxycycline and 62-71% for metronidazole. High levels of antibacterial activity up to 89-91% against Gardnerella vaginalis and 84-92% against Neisseria gonorrhoeae, were recorded in vitro for release media collected on day 14, compared to 'non-formulated' metronidazole and doxycycline solutions. Based on the in vitro data, the minimum...
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 ...
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.
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.
Journal of Materials Science: Materials in Medicine, 2013
Acyclovir (ACV) as a model antiviral microbicide, was incorporated in controlled-release polycaprolactone (PCL) matrices designed for application as intra-vaginal ring inserts (IVRs). Microporous materials incorporating acyclovir up to a level of *10 % w/w were produced by rapidly cooling suspensions of drug powder in PCL solution followed by solvent extraction from the hardened matrices. Around 21, 50 and 78 % of the drug content was gradually released from matrices over 30 days in simulated vaginal fluid at 37°C, corresponding to drug loadings of 5.9, 7.0 and 9.6 % w/w. The release behaviour of matrices having the lowest drug loading followed a zero order model, whereas, the release kinetics of 7.0 and 9.6 % ACV-loaded PCL matrices could be described effectively by the Higuchi model, suggesting that Fickian diffusion is controlling drug release. Corresponding values of the diffusion co-efficient for ACV in the PCL matrices of 3.16 9 10 -9 and 1.07 9 10 -8 cm 2 /s were calculated. Plaque reduction assays provided an IC 50 value of 1.09 lg/mL for acyclovir against HSV-2 and confirmed the antiviral activity of released acyclovir against HSV-2 replication in primate kidney cells (Vero) at levels *70 % that of non-formulated acyclovir at day 30. Estimated minimum in vivo acyclovir concentrations produced by a PCL IVR (19 lg/mL) exceeded by a factor of 20 the IC 50 value against HSV-2 and the reported ACV vaginal concentrations in women (0.5-1.0 lg/mL) following oral administration. These findings recommend further investigations of PCL matrices for vaginal delivery of antiviral agents in the treatment and prevention of sexually transmitted infections such as AIDS.
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.
Pharmaceutical development and technology, 2018
Microporous polymeric matrices prepared from poly(ɛ-caprolactone) [PCL] were evaluated for controlled vaginal delivery of the antiprotozoal agent (tinidazole) in the treatment of the sexually transmitted infection, trichomoniasis. The matrices were produced by rapidly cooling co-solutions of PCL and tinidazole in acetone to -80 °C to induce crystallisation and hardening of the polymer. Tinidazole incorporation in the matrices increased from 1.4 to 3.9% (w/w), when the drug concentration in the starting PCL solution was raised from 10 to 20% (w/w), giving rise to drug loading efficiencies up to 20%. Rapid 'burst release' of 30% of the tinidazole content was recorded over 24 h when the PCL matrices were immersed in simulated vaginal fluid. Gradual drug release occurred over the next 6 days resulting in delivery of around 50% of the tinidazole load by day 7 with the released drug retaining antiprotozoal activity at levels almost 50% that of the 'non-formulated' drug in ...
Formulation and evaluation of metronidazole acid gel for vaginal contraception
Journal of Pharmacy and Pharmacology, 2003
In this study, the efficacy of metronidazole as a local spermicidal agent was investigated. The drug was formulated in a concentration of 5% as an acid gel for vaginal application as a local contraception. The minimum spermicidal concentration of metronidazole was evaluated in-vitro and found to be 0.2% w/v. The formulated gel showed instant immobilization and death of all sperm within 30 s. A clinical study was conducted to determine the drug concentrations in vaginal secretions of healthy women and women with symptoms suggesting genital tract infection every 15 min for a 1-h period after application of 1 g of the gel in the vagina. Drug concentrations in the infected group were significantly lower (P < 0.05) than those in the healthy group at all time intervals. The drug concentrations in vaginal secretions after 1 h of vaginal medication remained above the determined minimum spermicidal concentration (0.2%) in the two groups. Measurement of vaginal pH before and after medication revealed a significant drop (P < 0.05) in pH to its normal value in both healthy and infected groups as a result of gel application. In conclusion, the designed gel has potential advantages of achieving a long retention time and effective drug concentrations in the vagina for at least 1 h after application, and of maintaining vaginal pH within its normal range.