Formulation and Evaluation of Metronidazole Microspheres-Loaded Bioadhesive Vaginal Gel

Abstract

Objectives: 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 translucent gel. The optimized metronidazole microsphere formulation was dispersed into the gel base.Microspheres in gel formulations were evaluated for pH, viscosity, spreadability, drug content, and gelling strength. Ex vivo mucoadhesive strength ofthe gel was determined on goat vaginal mucosa. In vitro drug release study was performed using cellophane membrane.Results: The optimized batch of microsphere F4 (drug-polymer ratio 1:4) showed entrapment efficiency of 72.62±3.66%, solubility of 1.5 mg/ml, andpartition coefficient of 0.12. Particle size of all the formulations was observed below 100 μm. Regular and spherical particles were observed in theSEM photomicrographs. The optimized gel formulation G5 (Carbopol and HPMC at 1: 0.25 ratio) showed viscosity of 7538 cps at 100 RPM, gel strengthrecorded as 35 secobds for a 1000.00 mg load, and spreadability of 4.6 g.cm/seconds. G5 showed 82.4% drug release at 10.0 hrs and mucoadhesivestrength of 6.5±1.2 g.Conclusion: The study results suggest that metronidazole-loaded PCL microsphere in mucoadhesive gel would provide a mean for sustainedtreatment of vaginal infections.Keywords: Microsphere, Metronidazole, Bioadhesive vaginal gel.

Tioconazole Loaded Mucoadhesive Microspheres for the Treatment of Vaginal Candidiasis

“…The results in This was in a great accordance with Kalita et al who found that metronidazole entrapment increased with an increase in HPMC K4 M concentration [4].…”

“…Hani et al formulated clotrimazole into intravaginal microspheres by the spray drying technique, which was inserted into a mucoadhesive gel for the local treatment of vaginal candidiasis [3]. Kalita et al increased the vaginal residence time of metronidazole through the preparation of PLC microspheres, which were incorporated into carbopol 934p and HPMC K4 M bioadhesive gel [4]. Khan and Thakur developed novel chitosan mucoadhesive microspheres for vaginal administration of tenofovir disproxil fumarate [5].…”

Formulation and Evaluation of Diazepam-Loaded Intravaginal Alginate Beads: An Investigation Study for the Treatment of Pelvic Floor Dysfunction

“…An increase in SA concentration led to an increase in the number of cross-linking points, so more drug would be entrapped and eventually a significant reduction in the total drug release from the resulting beads [39]. This could also be attributed to the formation of gelatinous mass on the surface of the formed beads on contact with the dissolution medium which hindered further penetration of the dissolution medium and increased the diffusional pass length [3,40].…”

“…The importance of the vagina as a route of drug administration comes from its rich blood supply, large surface area, high permeability to several drugs, in addition to the avoidance of the first-pass metabolism [3]. Mucoadhesion has been of great interest in the development of vaginal drug delivery systems to increase the residence time at the site of absorption [4].…”

Clinical comparative study of optimized metronidazole loaded lipid nanocarrier vaginal emulgel for management of bacterial vaginosis and its recurrence

“…Bacterial vaginosis (BV) is considered to be a major cause of vaginal discharge in females of childbearing age (Kenyon et al., 2013 ). BV is a clinical disorder recognized by a change in vaginal flora away from Lactobacillus species; which normally produce the lactic acid and hydrogen peroxide that maintain the acidic pH; toward various bacterial species, including different anaerobes such as Peptostreptococcus sp., Gardnerella vaginalis , Mycoplasma hominis , Staphylococcus sp., and the Enterobacteriaceae (Pandey et al., 2020 ).…”