Locust Bean Gum and Chitosan on Metronidazole as Biopolymer Composite for Improved Colon Specific Drug Delivery

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Onugba, Joseph C. Oguegbulu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9499388/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Biopolymers like locust bean gum (LBG) and chitosan have been useful in developing controlled-release matrices for drugs. In this work, efforts were made to develop a biopolymer composite of chitosan and LBG as coating films on metronidazole for improved colon-specific delivery. Four coating levels of Chitosan/LBG coating solution, F1, F2, F3 and F4 , corresponding to 10%, 20%, 30% and 40%, respectively, of average tablet weight were prepared. A dip-coating method was used to coat metronidazole tablets in triplicates with the biopolymeric system. Simulated colonic fluid (pH 6.8) and simulated gastric fluid (pH 1.2) were prepared and used for drug release studies. F4-coated tablets (40% average tablet weight) showed the most controlled release in colonic medium (SCF), with the lowest drug release of 60.3% after 30 minutes, slowly peaking to 99.3% after 210 minutes. Paradoxically, an inverse relationship was observed between coating levels and %drug release in SGF (pH 1.2), with the highest maximum drug release after one hour (47.8%) observed for F4 coated tablets, followed by F3 (43.9%), F2 (34.9%), and F1 (30.6%). Overall, the coated tablets show significantly higher maximum % drug release (p = < 0.05) in colonic medium (SCF) (pH 6.8), compared to gastric medium (SGF), suggesting that our biopolymer system may be capable of controlled release of metronidazole and better delivery to the colonic site of action over gastric release. These findings hold strong implications for biopolymer composites in pharmaceutical formulations and drug delivery, improvement of metronidazole efficacy and larger implications for other drug formulations. Drug Delivery Biopolymers Locust Bean Gum Chitosan Dissolution Studies Drug Delivery Clostridium Difficile Figures Figure 1 Figure 2 Figure 3 Figure 4 Background In the treatment of clostridium difficile infections (CDI) which are responsible for 20% of diarrheal diseases [ 1 ], there have been reports of reduced efficacy of metronidazole – the erstwhile first line treatment for mild to moderate severe diarrhea [ 2 , 3 ]. This observation has been explained, first by a rise in the minimum inhibitory concentration (MIC) of metronidazole for this infection (perhaps due to resistance dynamics) and secondly as due to insufficient levels of metronidazole reaching the colon – the primary site of action [ 4 ]. Whereas the efficacy of metronidazole in the management of this disease and others is reduced due to drug delivery and availability issues, vancomycin shows more potency in the treatment of these conditions and is known to reach higher concentrations at the site of action than metronidazole. Early release of metronidazole to the upper gastrointestinal tract poses a challenge to targeted delivery of the drug, resulting in reduced therapeutic efficiency and potential side effects in the management of CDI and diarrheal infections. It therefore suggests that the improvement of metronidazole delivery can increase its efficacy [ 5 , 6 ]. The use of efficient Colon Specific Drug Delivery Systems (CSDSS) to maximize metronidazole’s therapeutic benefit and reduce systemic adverse effects is a recent strategy that seeks to improve the treatment of severe CDI [ 7 ]. Drug delivery systems incorporating therapeutic agents to ensure better availability of drugs at the specific targets are an important area of ongoing research [ 8 ]. An ideal drug delivery system should have the ability to deliver the loaded drug to the specific area and regulate drug release with the goal of reducing promiscuous drug activity and side effects [ 9 ]. Biopolymers composed of series of covalently linked monomers [ 10 ] have been utilized in drug delivery systems to varying degrees and success. Some biopolymers have more recently gained attention for their pharmaceutical applicability in the design and fabrication of drug delivery systems [ 11 ]. Their unique applications in a variety of novel formulations can be attributed to properties such as biodegradability, availability, a capacity for modification of their physicochemical properties, and their general eco-friendliness [ 12 , 13 ]. Chitosan – a linear polysaccharide derived from chitin – as well as locust bean gum (LBG), which consists chiefly of natural galactose- and mannose-based polysaccharide, have been previously employed in various drug delivery systems [ 14 ], with advantages ranging from control of drug release, improved biocompatibility, and better targeting of drug delivery vehicles to specific sites [ 15 ]. Chitosan has been classed as safe (“Generally Recognized as Safe" (GRAS)) and approved for use in drug delivery applications by the FDA with LD 50 greater than 16 g/kg in mice [ 16 ]. LBG obtained from the seeds of the ceratonia siliqua tree, has shown useful applications in drug delivery systems ranging from tablets to capsules, beads, microspheres, gels, and polymeric films, with its conventional use mostly based on gel-forming and stabilizing properties [17.18]. The reported use of LBG in metronidazole delivery systems is due to its biocompatibility and ability to protect metronidazole from premature release in the upper gastrointestinal tract, ensuring higher concentrations of the drug in the colon [ 7 ]. Biopolymer composites involving LBG have also been applied in controlled release matrix technologies to good effect [ 19 ]. In the work of Dionisio, M. and Grenha, A [ 17 ], LBG/Xanthan gum (1:1) (50%) was successfully applied in pain management therapy. Locust bean gum, being rich in hydroxyl groups, is able to gel synergistically with biopolymers such as chitosan to form uniform, strong continuous networks and functional films without crack or pores [ 20 ]. Meanwhile, Mazumder and others [ 21 ] reported that satrinadazole multi-unit pallets prepared in chitosan, LBG and xanthan gum composites achieved 81.69% bioavailability due to spectacular controlled release in intestinal medium and significantly higher colonic drug content than free administered drug. In the current study, fresh efforts were made to develop a biopolymer coating system using locust bean gum (LBG) and chitosan (CTS) to enhance the controlled release of metronidazole for colon targeting in the treatment of CDI conditions. Materials and Methods A. Materials Pure metronidazole API was obtained from the laboratory of the Department of Pharmaceutics and Pharmaceutical Technology of Bingham University, Karu, Nasarawa State. Chitosan was a gift from a colleague at the Department of Pharmaceutical and Medicinal Chemistry, Bingham University, Karu. Market-available metronidazole tablets were sourced over the counter. Locust bean plant was sourced from Auta-Balefi, in Karu Local Government Area of Nasarawa State, Nigeria. All reagents used were of analytical grade. B. Processing of locust bean gum (Acid Peeling Process) The locust bean seeds contained within their pods were removed from the pods, thoroughly washed and processed by carbonization under heat treatment. This was achieved by exposure to 0.75M sulfuric acid at 100℃ for 2 hours. The seeds were then scrapped off to reveal bare endosperm, and the kernels were removed from the hulls and dried in an oven at 80 0 C. They were carefully cracked open and pulverized in a blender to give an off-white gum which was stored at 4 0 C for further use. C. Fourier transform infrared spectroscopy A ThermoFisher FTIR spectrophotometer was used to record the infrared (IR) spectra of the biopolymers utilizing the KBr pellet technique. The FTIR spectra obtained for LBG, and chitosan were compared to reference. D. Preparation of polymeric coating solution Polymeric coating materials were prepared by dissolving an amount of chitosan corresponding to one third (1/3) of 10%, 20%, 30%, and 40% of average tablet weight (for coating levels F1, F2, F3 and F4 respectively) , in corresponding volumes of acetic acid (1% v/v) with continuous stirring until a homogeneous solution was obtained. Similarly, locust bean gum corresponding to two thirds (2/3) of 10%, 20%, 30%, and 40% of average tablet weight was dissolved in corresponding volumes of distilled water, while heating gently on a magnetic stirrer to ensure solubility. Average tablet weight was obtained as the mean of the weight of three random tablets. The two solutions were combined to obtain a final solution of 1:2 Chitosan/LBG for the coating process. A volume of plasticizer (Glycerol) equivalent to 25% of polymeric coating solution was added for each coating level and mixed. E. Metronidazole tablet coating A dip-coating method was used to coat three (3) metronidazole tablets (400 mg) each in the four (4) different coating levels (F1 – F4) of 10%, 20%, 30% and 40% average tablet weight. The three (3) tablets for each coating level were dipped in the coating solution for 2 min, removed and dried in the oven for 2 hrs (Fig. 1 ). F. Preparation of simulated gastric and colonic fluids without enzyme Simulated colonic fluid (SCF) was prepared according to the United State Pharmacopeia, 2012 [ 22 ]. Potassium dihydrogen phosphate (KH 2 PO 4 ) (29.54 g) was dissolved in distilled water (1.3 L). 1.25 L of the solution was placed in a 5 L volumetric flask and 0.2 M NaOH (0.56 L) was added to adjust the pH of the solution to 6.8. Water was then added to volume. Conversely, 0.1N HCl was used in lieu of simulated gastric fluid (SGF). G. Determination of λ max and calibration curve of metronidazole in simulated gastric fluid (SGF) and simulated colonic fluid (SCF) media A stock solution of 5 mg/10 ml was made by dissolving pure metronidazole (5 mg) in SGF (10 ml). Double dilution was used to prepare the standard solutions which were made by diluting the stock solution (5 ml) with SGF (5 ml). Dilutions of 2.5 mg/ml, 1.25 mg/ml, 0.625 mg/ml, 0.3125 mg/ml, 0.1562 mg/ml, 0.0781 mg/ml, 0.0390 mg/ml, 0.0195 mg/ml, and 0.0098 mg/ml were further prepared. Standard solutions were prepared by dissolving metronidazole (5 mg) in methanol (5 ml) and then SCF (5ml) fluid. The same was done in SGF. To determine the maximum wavelength (λ max ) of metronidazole in both mediums, the respective solvents used in the preparation of both standards were used as blanks. The standards were added to a cuvette, and the solution of 0.0098 mg/ml concentration was added to another cuvette. A wavelength scan from 400–800 nm was run on the solution using a BIOBASE – BK-D580 UV spectrophotometer and a graph of the wavelengths to their absorbance was obtained. The calibration curve was prepared by reading the absorbance of all standards solutions at 278 nm for SGF and 274.6 nm for SCF from the solution with lowest concentration to the highest concentration. A Beer’s plot of the concentration of the standard solution against absorbance was plotted and a line of best fit determined as y = mx + b. H. In-vitro drug release studies The drug release study was done using a USP paddle type dissolution device with 800 ml of dissolution fluid at 37°C ± 0.5°C, stirred at 100 rpm. The dissolution technique was performed by altering the pH of the dissolution medium at different time intervals while maintaining proper sink conditions. Coated tablets corresponding to 400 mg were dissolved in 800 ml of medium at pH 1.2 in SGF for 1 hr and pH 6.8 in SCF for 4 hrs. 23 At different time intervals, 1 ml of each sample was withdrawn and replaced with the same amount of medium in the basket. The volume was increased to 40 ml for SGF and 30 ml for the SCF medium. Thereafter, the drug contents were measured at 278 nm (SGF samples) and 274.6 nm (SCF samples), using a BIOBASE–BK-D580 UV spectrophotometer. The dissolution process was done for 1hr in SGF and the medium was immediately replaced with SCF and continued for next 4hrs. Results and Discussion Locust bean gum was obtained as an off-white gummy material with a percentage yield of 43.6% which is similar to Dakia et al . [ 24 ]. As seen in Fig. 2 , the FTIR spectrum of the obtained LBG showed its characteristic O-H stretching peak at 3280 cm -1 , the asymmetric stretching of ether (C–C and C–O) around 1059 cm -1 , the alkyl C-H peaks at 2851–2920 cm -1 and 1624 cm -1 (C–H rocking and C–C stretching). Chitosan on the other hand showed characteristic N-H and O-H stretching around 3291 cm -1 and 1557 cm -1 (N-H bend) with the alkyl C-H peaks at 2871 cm -1 and 1644 cm -1 (C–H rocking and C–C stretching). Analysis of the FTIR spectra showing distinct peaks for different groups on the biopolymers suggests that the polymers would remain chemically different within the composite, having been physically mixed, as variously and previously reported [ 25 ]. A. Metronidazole tablet coating The preparation of coating solutions was successfully done to give F1, F2, F3, and F4 corresponding to 10%, 20%, 30% and 40% of average table weights respectively. The four (4) batches were arranged according to formulation components with 1:2 ratio of chitosan to LBG polymeric coating for each as presented in Table 1 . The three metronidazole tablets dip-coated at each coating level presented with film formation after drying to constant weight. Table 1 Coating composition for F1 - F4 with 1:2 ratio of chitosan (CTS) to locust bean gum (LBG) Batch code % of avg. table weight (%) Average weight of 3 random tablets Total Coating weight (mg) (CTS + LBG) CTS coating weight (mg) (CTS 1:2 LBG) x 3 tablets LBG coating weight (mg) (CTS 1:2 LBG) x 3 tablets F1 10 662 66.2 66.3 132.3 F2 20 652 130.4 130.5 260.7 F3 30 668 200.4 200.4 400.8 F4 40 653 261.2 261.3 522.3 B. Calibration Curves of Metronidazole in SGF and SCF media The maximum wavelength of absorption (λ max ) of the drug in SGF and SCF, upon measurement on a spectrophotometre were obtained as 278 nm and 274.6 nm respectively. The calibration curves of pure metronidazole in SGF and SCF are shown in Fig. 3. Figure 3: a) Calibration curve of biopolymer-coated metronidazole in simulated gastric fluid. b) Calibration curve of biopolymer-coated metronidazole in simulated colonic fluid. The Beer’s plot shows intercepts near zero in both scenarios and slopes of 0.092 and 0.036 for SGF and SCF media respectively C. In-vitro drug release studies The determination of drug amounts dissolved in SGF or SCF media at different time intervals for each the four coating levels F1 – F4 was done using equations 1 and 2: \(\:y=0.092*x\) (SGF medium) - - - - - - - - - (1) \(\:y=0.036*x\) (SCF medium) - - - - - - - - - (2) Where y = Absorbance, x = Concentration (µg/ml) The absorbance readings of coated sample drugs in SGF and SCF at different time intervals are presented in Tables 2 and 3 . Table 2 Absorbance of dip coated drug in SGF medium at different time intervals Batch code Abs 5 min Abs 10 mins Abs 15 mins Abs 30 mins Abs 45 mins Abs 60 mins F1 0.163 0.234 0.276 0.315 0.341 0.352 F2 0.198 0.243 0.280 0.321 0.354 0.401 F3 0.202 0.278 0.291 0.344 0.364 0.505 F4 0.230 0.289 0.294 0.390 0.461 0.550 Table 3 Absorbance of dip coated drug in SCF medium at different time intervals Batch code Abs 30 min Abs 60 min Abs 120 min Abs 180 mins Abs 210 mins F1 0.482 0.486 0.518 0.577 0.580 F2 0.472 0.513 0.520 0.568 0.587 F3 0.499 0.596 0.601 0.610 0.612 F4 0.392 0.522 0.537 0.566 0.596 The amount of drug dissolved for both media was therefore calculated accordingly as; \(\:Amount\:Dissolved=C*BV*\left(\frac{DF}{1000}\right)\) - - − 3 Where C = Concentration, BV = Bar Volume (800ml), DF = Dilution factor (40 in SGF medium and 30 in SCF medium) And the percentage of drug released as follows; \(\:\%\:Drug\:Released=\frac{Amount\:dissolved}{Drug\:amount\:\left(400\:mg\right)}*100\) - − 4 The dissolution curves for dip-coated drugs in SGF and SCF are presented in Fig. 4. Overall drug release profiles of coated tablets show a statistically significantly higher maximum % drug release (p = 0.003 < 0.05) in colonic medium (SCF) compared to gastric medium (SGF), suggesting that our biopolymer system may be capable of controlled release of metronidazole and better delivery to the colonic site of action over gastric release. In SCF (pH 6.8), F4-coated tablets (40% average tablet weight) showed the most controlled release with the lowest drug release of 60.3% after 30 minutes, slowly peaking to 99.3% after 210 minutes. Meanwhile, F3-coated tablets (30% average tablet weight) inexplicably showed the maximum possible drug release (100%), peaking after 1hr. Paradoxically, there seemed to be an inverse relationship between coating levels and % drug release in SGF (pH 1.2). A maximum drug release of 47.8% after one hour was observed for F4 coated tablets, followed by F3-coated tables (43.9%) and F2 tablets (34.9%), while F1 coated tablets (30.6%) showed the minimum drug release. This appears counterintuitive and in contrast to previous findings [ 21 ]. Figure 4 a) In vitro drug release profile in SGF medium b) In vitro drug release profile in SFC medium It may be attributed to issues with plasticiser-to-polymer ratio, especially going from thinner to thicker coatings. With Chitosan/LBG, plasticiser concentrations optimal for thin coats may be insufficient for thicker coats, leading to film flexibility and permeability and allowing faster drug release. Furthermore, pH may play a role in the dissolution or degradation of coatings as much as the ionic character of metronidazole. The pH-sensitive Chitosan may dissolve more in acidic conditions while the hydrophilic LBG may increase swelling, synergistically leading to potential coating failure, drug solubilization and release. Alternatively, the observation may be more simply attributable to composition issues in our simulated gastric fluid with the absence of such components as KCl, KH 2 PO 4 , NaHCO 3 , NaCl, MgCl 2 (H 2 O) 6 , (NH 4 ) 2 CO 3 , HCl, CaCl 2 (H 2 O 2 ) 2 in the preparation of our SGF [ 26 ]. Conclusion Further efforts on this theme will be focused on studies of the physicochemical properties of the biopolymer composite to provide further insight into optimum matrix parameters such as coating ratios, thickness, stability, environmental conditions as well as providing ideas for suitable new polysaccharides and biopolymer composites. Studies of drug-polymer interactions, in vivo pharmacokinetic and pharmacodynamic studies, colon-targeting efficiency in animal models, biocompatibility and toxicology will elucidate system performance for pharmaceutical applications. In the current study, the overall drug release profiles of our biopolymer coated tablets show significantly higher drug release in colonic medium compared to gastric medium suggesting site specific delivery. This holds strong implications for applications of biopolymer composites in pharmaceutical formulations and drug delivery, as well as for the improvement of metronidazole efficacy in managing infections. Declarations Conflict Of Interest The authors declare no conflict of interest. Funding The authors received no funding for this work. Author Contributions The authors have accepted responsibility for the entire content of this manuscript and approved its submission. 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Food Hydrocoll 22(5):807–818. https://doi.org/10.1016/j.foodhyd.2007.03.007 Grala D, Biernacki K, Freire C et al (2022) Effect of Natural Deep Eutectic Solvent and Chitosan Nanoparticles on Physicochemical Properties of Locust Bean Gum Films. Food Hydrocoll 126:107460. https://doi.org/10.1016/j.foodhyd.2021.107460 Brodkorb A, Egger L, Alminger M et al (2019) INFOGEST Static in Vitro Simulation of Gastrointestinal Food Digestion. Nat Protoc 14(4):991–1014. https://doi.org/10.1038/s41596-018-0119-1 Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9499388","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":627942957,"identity":"7a7cfcbf-51be-4505-9dcc-4ab57a7943f2","order_by":0,"name":"TItus E. Onugba","email":"","orcid":"https://orcid.org/0009-0000-1096-3503","institution":"Department of Chemical Sciences, Bingham University, Karu., Nigeria","correspondingAuthor":false,"prefix":"","firstName":"TItus","middleName":"E.","lastName":"Onugba","suffix":""},{"id":627943044,"identity":"d7869c68-2c89-49e9-b6ff-f71337fb17fd","order_by":1,"name":"Joseph C. Oguegbulu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABYElEQVRIie3RPWsCMRgH8OcIOJ245jjUr3ASsC1KP0ehi4egi0d7yy0dGhByi7RrpEP7ESxCcfS4oYvoeqCDItihi0VaLKXQnFdfAoJrofcfQhLyI0+eAMSJ8wej0PUgggCOIYXFMtoJx8RBgkHjB8jWrYkR7OzsI8h1J1O7A5nsWdl/tRk228M6m7x3Ts+NYZ3C3PHhKPUgXdDoEdLsAckFlUqhKcjTyHNJule2WiOPKrzvwwkfS4TXEnqSgfnIa3mSDElgMl1jyGoFJkVJ5otSuzKpvnxF5OJjRdp8Ra4j8r2PlPIoJPe4hqYhaWGTaW/Mj4gSkgGViHiLLp5ADHWWR7yPCR95TFfYs9UUxGv0q+qqh9vkRMcWNitmsm55urh0iunbO3emfbIr6yaoTsZLp5AxBlJhObr+ji4k8Kb16u8kPKsCLu2SbPSDYkIBzTflLqVSUtItceLEifPv8gNeYokZkwhiTQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-3787-4628","institution":"Department of Chemical Sciences, Bingham University, Karu, Nigeria","correspondingAuthor":true,"prefix":"","firstName":"Joseph","middleName":"C.","lastName":"Oguegbulu","suffix":""}],"badges":[],"createdAt":"2026-04-22 17:53:29","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9499388/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9499388/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107869896,"identity":"2bb7fa18-32c9-4062-a0f0-1b632ccd0ec4","added_by":"auto","created_at":"2026-04-27 07:38:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":105256,"visible":true,"origin":"","legend":"\u003cp\u003eDip coating process of metronidazole tablet\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9499388/v1/3f68e2dfab5ed7cb65f98ce6.png"},{"id":107750970,"identity":"18a82b3d-dca9-4ed0-89e1-46516cf0f3b5","added_by":"auto","created_at":"2026-04-24 17:16:55","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":95279,"visible":true,"origin":"","legend":"\u003cp\u003ea) FTIR curve of LBG. \u0026nbsp;b) FTIR Curve of Chitosan\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9499388/v1/5a6a5ae56184e86bd1e2ad00.jpg"},{"id":107869183,"identity":"8f5a4673-b425-4be2-bc1d-355144dcdd0b","added_by":"auto","created_at":"2026-04-27 07:36:21","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":93450,"visible":true,"origin":"","legend":"\u003cp\u003e\u0026nbsp;a) Calibration curve of biopolymer-coated metronidazole in simulated gastric fluid\u003cstrong\u003e. \u0026nbsp;\u003c/strong\u003eb) Calibration curve of biopolymer-coated metronidazole in simulated colonic fluid.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9499388/v1/82caf759aa4451a4ad271870.jpg"},{"id":107750972,"identity":"2446fd5a-957b-4197-a12e-e44839c37e2c","added_by":"auto","created_at":"2026-04-24 17:16:55","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":97056,"visible":true,"origin":"","legend":"\u003cp\u003ea) In vitro drug release profile in SGF medium b) In vitro drug release profile in SFC medium\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9499388/v1/c647c9606537c6b491c85f51.jpg"},{"id":107872192,"identity":"ab19cb8a-5f24-4637-8eb0-2f3fd060a994","added_by":"auto","created_at":"2026-04-27 07:56:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":657140,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9499388/v1/74966125-cf9f-4a45-9065-b90d9285387d.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eLocust Bean Gum and Chitosan on Metronidazole as Biopolymer Composite for Improved Colon Specific Drug Delivery\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eIn the treatment of \u003cem\u003eclostridium difficile\u003c/em\u003e infections (CDI) which are responsible for 20% of diarrheal diseases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], there have been reports of reduced efficacy of metronidazole \u0026ndash; the erstwhile first line treatment for mild to moderate severe diarrhea [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This observation has been explained, first by a rise in the minimum inhibitory concentration (MIC) of metronidazole for this infection (perhaps due to resistance dynamics) and secondly as due to insufficient levels of metronidazole reaching the colon \u0026ndash; the primary site of action [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Whereas the efficacy of metronidazole in the management of this disease and others is reduced due to drug delivery and availability issues, vancomycin shows more potency in the treatment of these conditions and is known to reach higher concentrations at the site of action than metronidazole.\u003c/p\u003e \u003cp\u003eEarly release of metronidazole to the upper gastrointestinal tract poses a challenge to targeted delivery of the drug, resulting in reduced therapeutic efficiency and potential side effects in the management of CDI and diarrheal infections. It therefore suggests that the improvement of metronidazole delivery can increase its efficacy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The use of efficient Colon Specific Drug Delivery Systems (CSDSS) to maximize metronidazole\u0026rsquo;s therapeutic benefit and reduce systemic adverse effects is a recent strategy that seeks to improve the treatment of severe CDI [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Drug delivery systems incorporating therapeutic agents to ensure better availability of drugs at the specific targets are an important area of ongoing research [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. An ideal drug delivery system should have the ability to deliver the loaded drug to the specific area and regulate drug release with the goal of reducing promiscuous drug activity and side effects [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBiopolymers composed of series of covalently linked monomers [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] have been utilized in drug delivery systems to varying degrees and success. Some biopolymers have more recently gained attention for their pharmaceutical applicability in the design and fabrication of drug delivery systems [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Their unique applications in a variety of novel formulations can be attributed to properties such as biodegradability, availability, a capacity for modification of their physicochemical properties, and their general eco-friendliness [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Chitosan \u0026ndash; a linear polysaccharide derived from chitin \u0026ndash; as well as locust bean gum (LBG), which consists chiefly of natural galactose- and mannose-based polysaccharide, have been previously employed in various drug delivery systems [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], with advantages ranging from control of drug release, improved biocompatibility, and better targeting of drug delivery vehicles to specific sites [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Chitosan has been classed as safe (\u0026ldquo;Generally Recognized as Safe\" (GRAS)) and approved for use in drug delivery applications by the FDA with LD\u003csub\u003e50\u003c/sub\u003e greater than 16 g/kg in mice [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLBG obtained from the seeds of the \u003cem\u003eceratonia siliqua\u003c/em\u003e tree, has shown useful applications in drug delivery systems ranging from tablets to capsules, beads, microspheres, gels, and polymeric films, with its conventional use mostly based on gel-forming and stabilizing properties [17.18]. The reported use of LBG in metronidazole delivery systems is due to its biocompatibility and ability to protect metronidazole from premature release in the upper gastrointestinal tract, ensuring higher concentrations of the drug in the colon [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Biopolymer composites involving LBG have also been applied in controlled release matrix technologies to good effect [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In the work of Dionisio, M. and Grenha, A [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], LBG/Xanthan gum (1:1) (50%) was successfully applied in pain management therapy. Locust bean gum, being rich in hydroxyl groups, is able to gel synergistically with biopolymers such as chitosan to form uniform, strong continuous networks and functional films without crack or pores [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Meanwhile, Mazumder and others [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] reported that satrinadazole multi-unit pallets prepared in chitosan, LBG and xanthan gum composites achieved 81.69% bioavailability due to spectacular controlled release in intestinal medium and significantly higher colonic drug content than free administered drug. In the current study, fresh efforts were made to develop a biopolymer coating system using locust bean gum (LBG) and chitosan (CTS) to enhance the controlled release of metronidazole for colon targeting in the treatment of CDI conditions.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eA. Materials\u003c/h2\u003e \u003cp\u003ePure metronidazole API was obtained from the laboratory of the Department of Pharmaceutics and Pharmaceutical Technology of Bingham University, Karu, Nasarawa State. Chitosan was a gift from a colleague at the Department of Pharmaceutical and Medicinal Chemistry, Bingham University, Karu. Market-available metronidazole tablets were sourced over the counter. Locust bean plant was sourced from Auta-Balefi, in Karu Local Government Area of Nasarawa State, Nigeria. All reagents used were of analytical grade.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eB. Processing of locust bean gum (Acid Peeling Process)\u003c/h3\u003e\n\u003cp\u003eThe locust bean seeds contained within their pods were removed from the pods, thoroughly washed and processed by carbonization under heat treatment. This was achieved by exposure to 0.75M sulfuric acid at 100℃ for 2 hours. The seeds were then scrapped off to reveal bare endosperm, and the kernels were removed from the hulls and dried in an oven at 80 \u003csup\u003e0\u003c/sup\u003eC. They were carefully cracked open and pulverized in a blender to give an off-white gum which was stored at 4\u003csup\u003e0\u003c/sup\u003eC for further use.\u003c/p\u003e\n\u003ch3\u003eC. Fourier transform infrared spectroscopy\u003c/h3\u003e\n\u003cp\u003eA ThermoFisher FTIR spectrophotometer was used to record the infrared (IR) spectra of the biopolymers utilizing the KBr pellet technique. The FTIR spectra obtained for LBG, and chitosan were compared to reference.\u003c/p\u003e\n\u003ch3\u003eD. Preparation of polymeric coating solution\u003c/h3\u003e\n\u003cp\u003ePolymeric coating materials were prepared by dissolving an amount of chitosan corresponding to one third (1/3) of 10%, 20%, 30%, and 40% of average tablet weight \u003cem\u003e(for coating levels F1, F2, F3 and F4 respectively)\u003c/em\u003e, in corresponding volumes of acetic acid (1% v/v) with continuous stirring until a homogeneous solution was obtained. Similarly, locust bean gum corresponding to two thirds (2/3) of 10%, 20%, 30%, and 40% of average tablet weight was dissolved in corresponding volumes of distilled water, while heating gently on a magnetic stirrer to ensure solubility. Average tablet weight was obtained as the mean of the weight of three random tablets.\u003c/p\u003e \u003cp\u003eThe two solutions were combined to obtain a final solution of 1:2 Chitosan/LBG for the coating process. A volume of plasticizer (Glycerol) equivalent to 25% of polymeric coating solution was added for each coating level and mixed.\u003c/p\u003e\n\u003ch3\u003eE. Metronidazole tablet coating\u003c/h3\u003e\n\u003cp\u003eA dip-coating method was used to coat three (3) metronidazole tablets (400 mg) each in the four (4) different coating levels (F1 \u0026ndash; F4) of 10%, 20%, 30% and 40% average tablet weight. The three (3) tablets for each coating level were dipped in the coating solution for 2 min, removed and dried in the oven for 2 hrs (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eF. Preparation of simulated gastric and colonic fluids without enzyme\u003c/h2\u003e \u003cp\u003eSimulated colonic fluid (SCF) was prepared according to the United State Pharmacopeia, 2012 [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Potassium dihydrogen phosphate (KH\u003csub\u003e2\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e) (29.54 g) was dissolved in distilled water (1.3 L). 1.25 L of the solution was placed in a 5 L volumetric flask and 0.2 M NaOH (0.56 L) was added to adjust the pH of the solution to 6.8. Water was then added to volume. Conversely, 0.1N HCl was used in lieu of simulated gastric fluid (SGF).\u003c/p\u003e \u003cp\u003e \u003cem\u003eG. Determination of λ\u003c/em\u003e \u003csub\u003e \u003cem\u003emax\u003c/em\u003e \u003c/sub\u003e \u003cem\u003eand calibration curve of metronidazole in simulated gastric fluid (SGF) and simulated colonic fluid (SCF) media\u003c/em\u003e\u003c/p\u003e \u003cp\u003eA stock solution of 5 mg/10 ml was made by dissolving pure metronidazole (5 mg) in SGF (10 ml). Double dilution was used to prepare the standard solutions which were made by diluting the stock solution (5 ml) with SGF (5 ml). Dilutions of 2.5 mg/ml, 1.25 mg/ml, 0.625 mg/ml, 0.3125 mg/ml, 0.1562 mg/ml, 0.0781 mg/ml, 0.0390 mg/ml, 0.0195 mg/ml, and 0.0098 mg/ml were further prepared. Standard solutions were prepared by dissolving metronidazole (5 mg) in methanol (5 ml) and then SCF (5ml) fluid. The same was done in SGF.\u003c/p\u003e \u003cp\u003eTo determine the maximum wavelength (λ\u003csub\u003emax\u003c/sub\u003e) of metronidazole in both mediums, the respective solvents used in the preparation of both standards were used as blanks. The standards were added to a cuvette, and the solution of 0.0098 mg/ml concentration was added to another cuvette. A wavelength scan from 400\u0026ndash;800 nm was run on the solution using a BIOBASE \u0026ndash; BK-D580 UV spectrophotometer and a graph of the wavelengths to their absorbance was obtained. The calibration curve was prepared by reading the absorbance of all standards solutions at 278 nm for SGF and 274.6 nm for SCF from the solution with lowest concentration to the highest concentration. A Beer\u0026rsquo;s plot of the concentration of the standard solution against absorbance was plotted and a line of best fit determined as y\u0026thinsp;=\u0026thinsp;mx\u0026thinsp;+\u0026thinsp;b.\u003c/p\u003e \u003cp\u003e \u003cem\u003eH. In-vitro drug release studies\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe drug release study was done using a USP paddle type dissolution device with 800 ml of dissolution fluid at 37\u0026deg;C\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u0026deg;C, stirred at 100 rpm. The dissolution technique was performed by altering the pH of the dissolution medium at different time intervals while maintaining proper sink conditions. Coated tablets corresponding to 400 mg were dissolved in 800 ml of medium at pH 1.2 in SGF for 1 hr and pH 6.8 in SCF for 4 hrs.\u003csup\u003e23\u003c/sup\u003e At different time intervals, 1 ml of each sample was withdrawn and replaced with the same amount of medium in the basket. The volume was increased to 40 ml for SGF and 30 ml for the SCF medium. Thereafter, the drug contents were measured at 278 nm (SGF samples) and 274.6 nm (SCF samples), using a BIOBASE\u0026ndash;BK-D580 UV spectrophotometer. The dissolution process was done for 1hr in SGF and the medium was immediately replaced with SCF and continued for next 4hrs.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eLocust bean gum was obtained as an off-white gummy material with a percentage yield of 43.6% which is similar to Dakia \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. As seen in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the FTIR spectrum of the obtained LBG showed its characteristic O-H stretching peak at 3280 cm\u003csup\u003e-1\u003c/sup\u003e, the asymmetric stretching of ether (C\u0026ndash;C and C\u0026ndash;O) around 1059 cm\u003csup\u003e-1\u003c/sup\u003e, the alkyl C-H peaks at 2851\u0026ndash;2920 cm\u003csup\u003e-1\u003c/sup\u003e and 1624 cm\u003csup\u003e-1\u003c/sup\u003e (C\u0026ndash;H rocking and C\u0026ndash;C stretching).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eChitosan on the other hand showed characteristic N-H and O-H stretching around 3291 cm\u003csup\u003e-1\u003c/sup\u003e and 1557 cm\u003csup\u003e-1\u003c/sup\u003e (N-H bend) with the alkyl C-H peaks at 2871 cm\u003csup\u003e-1\u003c/sup\u003e and 1644 cm\u003csup\u003e-1\u003c/sup\u003e (C\u0026ndash;H rocking and C\u0026ndash;C stretching). Analysis of the FTIR spectra showing distinct peaks for different groups on the biopolymers suggests that the polymers would remain chemically different within the composite, having been physically mixed, as variously and previously reported [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eA. Metronidazole tablet coating\u003c/h3\u003e\n\u003cp\u003eThe preparation of coating solutions was successfully done to give F1, F2, F3, and F4 corresponding to 10%, 20%, 30% and 40% of average table weights respectively. The four (4) batches were arranged according to formulation components with 1:2 ratio of chitosan to LBG polymeric coating for each as presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The three metronidazole tablets dip-coated at each coating level presented with film formation after drying to constant weight.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCoating composition for F1 - F4 with 1:2 ratio of chitosan (CTS) to locust bean gum (LBG)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBatch code\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e% of avg. table weight (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAverage weight\u003c/p\u003e \u003cp\u003eof 3 random tablets\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal Coating weight (mg)\u003c/p\u003e \u003cp\u003e(CTS\u0026thinsp;+\u0026thinsp;LBG)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCTS coating weight (mg)\u003c/p\u003e \u003cp\u003e(CTS 1:2 LBG)\u003c/p\u003e \u003cp\u003ex 3 tablets\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLBG coating weight (mg)\u003c/p\u003e \u003cp\u003e(CTS 1:2 LBG)\u003c/p\u003e \u003cp\u003ex 3 tablets\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e662\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e66.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e66.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e132.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e652\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e130.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e130.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e260.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e668\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e200.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e200.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e400.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e653\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e261.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e261.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e522.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eB. Calibration Curves of Metronidazole in SGF and SCF media\u003c/h2\u003e \u003cp\u003eThe maximum wavelength of absorption (λ\u003csub\u003emax\u003c/sub\u003e) of the drug in SGF and SCF, upon measurement on a spectrophotometre were obtained as 278 nm and 274.6 nm respectively. The calibration curves of pure metronidazole in SGF and SCF are shown in Fig.\u0026nbsp;3.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003cp\u003eFigure\u0026nbsp;3: a) Calibration curve of biopolymer-coated metronidazole in simulated gastric fluid. b) Calibration curve of biopolymer-coated metronidazole in simulated colonic fluid.\u003c/p\u003e \u003cp\u003eThe Beer\u0026rsquo;s plot shows intercepts near zero in both scenarios and slopes of 0.092 and 0.036 for SGF and SCF media respectively\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eC. In-vitro drug release studies\u003c/h2\u003e \u003cp\u003eThe determination of drug amounts dissolved in SGF or SCF media at different time intervals for each the four coating levels F1 \u0026ndash; F4 was done using equations 1 and 2:\u003c/p\u003e \u003cp\u003e \u003cspan class=\"InlineEquation\"\u003e \u003cspan class=\"mathinline\"\u003e\\(\\:y=0.092*x\\)\u003c/span\u003e \u003c/span\u003e (SGF medium) - - - - - - - - - (1)\u003c/p\u003e \u003cp\u003e \u003cspan class=\"InlineEquation\"\u003e \u003cspan class=\"mathinline\"\u003e\\(\\:y=0.036*x\\)\u003c/span\u003e \u003c/span\u003e (SCF medium) - - - - - - - - - (2)\u003c/p\u003e \u003cp\u003e \u003cem\u003eWhere y\u0026thinsp;=\u0026thinsp;Absorbance, x\u0026thinsp;=\u0026thinsp;Concentration (\u0026micro;g/ml)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe absorbance readings of coated sample drugs in SGF and SCF at different time intervals are presented in Tables \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAbsorbance of dip coated drug in SGF medium at different time intervals\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBatch code\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e5 min\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e10 mins\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e15 mins\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e30 mins\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e45 mins\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e60 mins\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.234\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.341\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.352\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.198\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.354\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.401\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.278\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.344\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.505\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.289\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.294\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.390\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.461\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.550\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAbsorbance of dip coated drug in SCF medium at different time intervals\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBatch code\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e30 min\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e60 min\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e120 min\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e180\u003c/p\u003e \u003cp\u003emins\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbs\u003c/p\u003e \u003cp\u003e210\u003c/p\u003e \u003cp\u003emins\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.518\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.577\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.580\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.472\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.520\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.568\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.587\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.499\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.601\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.610\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.612\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.392\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.522\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.537\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.596\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe amount of drug dissolved for both media was therefore calculated accordingly as;\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:Amount\\:Dissolved=C*BV*\\left(\\frac{DF}{1000}\\right)\\)\u003c/span\u003e\u003c/span\u003e - - \u0026minus;\u0026thinsp;3\u003c/h2\u003e \u003cp\u003e \u003cem\u003eWhere C\u0026thinsp;=\u0026thinsp;Concentration, BV\u0026thinsp;=\u0026thinsp;Bar Volume (800ml), DF\u0026thinsp;=\u0026thinsp;Dilution factor (40 in SGF medium and 30 in SCF medium)\u003c/em\u003e \u003c/p\u003e \u003cp\u003eAnd the percentage of drug released as follows;\u003c/p\u003e \u003cp\u003e \u003cspan class=\"InlineEquation\"\u003e \u003cspan class=\"mathinline\"\u003e\\(\\:\\%\\:Drug\\:Released=\\frac{Amount\\:dissolved}{Drug\\:amount\\:\\left(400\\:mg\\right)}*100\\)\u003c/span\u003e \u003c/span\u003e - \u0026minus;\u0026thinsp;4\u003c/p\u003e \u003cp\u003eThe dissolution curves for dip-coated drugs in SGF and SCF are presented in Fig.\u0026nbsp;4. Overall drug release profiles of coated tablets show a statistically significantly higher maximum % drug release \u003cem\u003e(p\u0026thinsp;=\u0026thinsp;0.003\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/em\u003e in colonic medium (SCF) compared to gastric medium (SGF), suggesting that our biopolymer system may be capable of controlled release of metronidazole and better delivery to the colonic site of action over gastric release. In SCF (pH 6.8), F4-coated tablets (40% average tablet weight) showed the most controlled release with the lowest drug release of 60.3% after 30 minutes, slowly peaking to 99.3% after 210 minutes. Meanwhile, F3-coated tablets (30% average tablet weight) inexplicably showed the maximum possible drug release (100%), peaking after 1hr.\u003c/p\u003e \u003cp\u003eParadoxically, there seemed to be an inverse relationship between coating levels and % drug release in SGF (pH 1.2). A maximum drug release of 47.8% after one hour was observed for F4 coated tablets, followed by F3-coated tables (43.9%) and F2 tablets (34.9%), while F1 coated tablets (30.6%) showed the minimum drug release. This appears counterintuitive and in contrast to previous findings [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003cp\u003e \u003cstrong\u003eFigure\u0026nbsp;4\u003c/strong\u003e \u003cp\u003ea) In vitro drug release profile in SGF medium b) In vitro drug release profile in SFC medium\u003c/p\u003e \u003c/p\u003e \u003cp\u003eIt may be attributed to issues with plasticiser-to-polymer ratio, especially going from thinner to thicker coatings. With Chitosan/LBG, plasticiser concentrations optimal for thin coats may be insufficient for thicker coats, leading to film flexibility and permeability and allowing faster drug release. Furthermore, pH may play a role in the dissolution or degradation of coatings as much as the ionic character of metronidazole. The pH-sensitive Chitosan may dissolve more in acidic conditions while the hydrophilic LBG may increase swelling, synergistically leading to potential coating failure, drug solubilization and release. Alternatively, the observation may be more simply attributable to composition issues in our simulated gastric fluid with the absence of such components as KCl, KH\u003csub\u003e2\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e, NaHCO\u003csub\u003e3\u003c/sub\u003e, NaCl, MgCl\u003csub\u003e2\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003eO)\u003csub\u003e6\u003c/sub\u003e, (NH\u003csub\u003e4\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003eCO\u003csub\u003e3\u003c/sub\u003e, HCl, CaCl\u003csub\u003e2\u003c/sub\u003e(H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e in the preparation of our SGF [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFurther efforts on this theme will be focused on studies of the physicochemical properties of the biopolymer composite to provide further insight into optimum matrix parameters such as coating ratios, thickness, stability, environmental conditions as well as providing ideas for suitable new polysaccharides and biopolymer composites. Studies of drug-polymer interactions, \u003cem\u003ein vivo\u003c/em\u003e pharmacokinetic and pharmacodynamic studies, colon-targeting efficiency in animal models, biocompatibility and toxicology will elucidate system performance for pharmaceutical applications.\u003c/p\u003e \u003cp\u003eIn the current study, the overall drug release profiles of our biopolymer coated tablets show significantly higher drug release in colonic medium compared to gastric medium suggesting site specific delivery. This holds strong implications for applications of biopolymer composites in pharmaceutical formulations and drug delivery, as well as for the improvement of metronidazole efficacy in managing infections.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict Of Interest\u003c/h2\u003e \u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors received no funding for this work.\u003c/p\u003e\u003ch2\u003eAuthor Contributions\u003c/h2\u003e \u003cp\u003eThe authors have accepted responsibility for the entire content of this manuscript and approved its submission.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e \u003cp\u003eThe authors wish to acknowledge the National Institute of Pharmaceutical Research and Development (NIPRD), Idu, FCT, Nigeria for their cooperation and support on this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDi Bella S, Sanson G, Monticelli J (2024) Clostridioides Difficile Infection: History, Epidemiology, Risk Factors, Prevention, Clinical Manifestations, Treatment, and Future Options. 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Food Hydrocoll 126:107460. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.foodhyd.2021.107460\u003c/span\u003e\u003cspan address=\"10.1016/j.foodhyd.2021.107460\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrodkorb A, Egger L, Alminger M et al (2019) INFOGEST Static in Vitro Simulation of Gastrointestinal Food Digestion. Nat Protoc 14(4):991\u0026ndash;1014. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41596-018-0119-1\u003c/span\u003e\u003cspan address=\"10.1038/s41596-018-0119-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Bingham University, Karu","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Locust Bean Gum, Chitosan, Dissolution Studies, Drug Delivery, Clostridium Difficile","lastPublishedDoi":"10.21203/rs.3.rs-9499388/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9499388/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBiopolymers like locust bean gum (LBG) and chitosan have been useful in developing controlled-release matrices for drugs. In this work, efforts were made to develop a biopolymer composite of chitosan and LBG as coating films on metronidazole for improved colon-specific delivery. Four coating levels of Chitosan/LBG coating solution, \u003cem\u003eF1, F2, F3\u003c/em\u003e and \u003cem\u003eF4\u003c/em\u003e, corresponding to 10%, 20%, 30% and 40%, respectively, of average tablet weight were prepared. A dip-coating method was used to coat metronidazole tablets in triplicates with the biopolymeric system. Simulated colonic fluid (pH 6.8) and simulated gastric fluid (pH 1.2) were prepared and used for drug release studies. F4-coated tablets (40% average tablet weight) showed the most controlled release in colonic medium (SCF), with the lowest drug release of 60.3% after 30 minutes, slowly peaking to 99.3% after 210 minutes. Paradoxically, an inverse relationship was observed between coating levels and %drug release in SGF (pH 1.2), with the highest maximum drug release after one hour (47.8%) observed for F4 coated tablets, followed by F3 (43.9%), F2 (34.9%), and F1 (30.6%). Overall, the coated tablets show significantly higher maximum % drug release \u003cem\u003e(p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/em\u003e in colonic medium (SCF) (pH 6.8), compared to gastric medium (SGF), suggesting that our biopolymer system may be capable of controlled release of metronidazole and better delivery to the colonic site of action over gastric release. These findings hold strong implications for biopolymer composites in pharmaceutical formulations and drug delivery, improvement of metronidazole efficacy and larger implications for other drug formulations.\u003c/p\u003e","manuscriptTitle":"Locust Bean Gum and Chitosan on Metronidazole as Biopolymer Composite for Improved Colon Specific Drug Delivery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-24 17:16:51","doi":"10.21203/rs.3.rs-9499388/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b4174c91-b608-4940-9986-484439c70fb9","owner":[],"postedDate":"April 24th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":66837624,"name":"Drug Delivery"},{"id":66837625,"name":"Biopolymers"}],"tags":[],"updatedAt":"2026-04-24T17:16:52+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-24 17:16:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9499388","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9499388","identity":"rs-9499388","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}