DEVELOPMENT OF MULTIPARTICULATE METRONIDAZOLE USING POLYMER COMPOSITE OF SESAME LEAF AND OKRA POD GUMS FOR SUSTAINED RELEASE

Abstract: Background: Gastric retention and sustained drug delivery are targeted drug delivery systems aimed at achieving clinical outcomes that are farfetched with conventional drug delivery systems. This study aimed to design a sustained release hybrid multiparticulate metronidazole particulate delivery that is swell-able, floatable and bio-adhesive using natural polymer composites.

Methods: Sesame leaf and okra pod mucilages were precipitated with absolute ethanol (99%) and characterized for flow properties, swelling index, pH, proximate composition and compatibility using Fourier’s Transformed Infrared spectroscopy (FTIR). F1-F8 metronidazole multiparticulates were prepared by extruding the drug-polymer blend into a cross-linking agent. The polymer composites were made of  sodium alginate and sesame leaf gum or okra pod gum in 10:3, 5:2, 2:1 and a combination of all the polymers in 5:1:1 and 4:1:1 in which the polymer composites were pre-gelatinized at 50°C. The formed particles were evaluated for swelling index, floating properties, ex vivo bio-adhesion, effect of particle size and polymer concentration on drug release, morphology using scanned electron microscopy (SEM), X-ray diffraction (XRD) for compatibility and stability, drug content, entrapment efficiency and in-vitro dissolution studies.  

Results: The pH of sesame leaf and okra pod gums was 6.41±0.00 and 7.16±0.00 respectively, an acceptable biological range. Sesame leaf gum had a poorer flow property with Carr’s Index 50°±0.06 and Hausner’s ratio 1.67°±0.06, when compared with okra pod gum of Carr’s Index 19.4°±0.06 and Hausner’s ratio of 1.24°±0.06. Also, the swelling index of sesame leaf gum (1390±0.02%) was close to three times that of okra pod gum (480±0.03%). The FTIR showed no significant change between the spectra of dry powder mix and F7 (polymer composite 5:1:1) as the functional groups were consistent in all the spectra. The XRD showed no significant changes in the diffractograms as B type crystallinity occurred at 22° for pure metronidazole and F7. The percentage yield ranges from 19.6 to 30.3% and swelling index range 40.9 to 107.2% of the particles. Floating buoyancy was 74.5% for F4 and 10.2% for F8 while the floating lag time for F4 (polymer composite 10:3 of sodium alginate and okra pod gum) and F8 (polymer composite 4:1:1) were 336±29s and 933±45s respectively. The ex vivo bio-adhesion showed F3 (polymer composite 5:2 of sodium alginate and sesame leaf gum) and F7 with 129.3±8.1s and 941.7±40.1s detachment time respectively. Entrapment efficiencies also range from 34.2% to 51.7% with F2 having the highest drug entrapment. From the dissolution studies, 4.1-7.9µg/ml of metronidazole was constantly released over 24 h, and at 95% confidence interval using anova test, the particle size and the polymer concentration 4.8-6% w/v has statistically significant effect on the amount of drug release per time. Sustained release model was Higuchi’s and the mechanism of drug release was quasi-Fickian diffusion.

Conclusion: The metronidazole multiparticulates (sodium alginate and sesame leaf gum or okra pod gum in 10:3, 5:2, 2:1  and a combination of all polymers in 5:1:1 and 4:1:1) were all swellable and sustained release over 24 h maintaining a narrow range of release 4.1-7.9 mcg/ml per time. The best bio-adhesive formulation was F7 while best floating behavior was exhibited by F4 with floating buoyancy of 74.5% and the best swellable hollow spheres was F6.

Keywords: Sesame leaf gum, okra pod gum, sodium alginate, sustained release and Gastro retention.

Title: DEVELOPMENT OF MULTIPARTICULATE METRONIDAZOLE USING POLYMER COMPOSITE OF SESAME LEAF AND OKRA POD GUMS FOR SUSTAINED RELEASE

Author: Ogianakhu A.S., Azubuike C. P., Ologunagba M., Igwilo C. I.

International Journal of Novel Research in Healthcare and Nursing

ISSN 2394-7330

Vol. 10, Issue 2, May 2023 - August 2023

Page No: 58-76

Novelty Journals

Website: www.noveltyjournals.com

Published Date: 09-June-2023

DOI: https://doi.org/10.5281/zenodo.8020630

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