Optimization and validation of polyherbal formulation by applying Box-Behnken design for the treatment of Inflammatory bowel disease in experimental animals.

Background: The use of herbal medicine in inflammatory bowel disease (IBD) had been increased significantly. Allopathic treatment of IBD leads too many side effects therefore use of the herbal formulation is promising. Aegle Marmelos, Bombax malabericum, and Hollarrhena antidysentrica plants have been used to treat IBD. Objective: To evaluate a designed polyherbal formulation in experimentally induced inflammatory bowel disease in rats and To validate mathematical model derived by Box-Behnken experimental design for optimized polyherbal formulation for the treatment of IBD in experimental rats by checkpoint analysis. Method: Three-level Box-Behnken design was selected to optimize the dose. Polyherbal formulation consist of plant extract of Aegle Marmelos (X1), Bombax malabericum (X2), and Hollarrhena antidysentrica (X3) in different ratios were selected as independent variable. Polynomial equations were established based on Analysis of variance (ANOVA). To validate the chosen polynomial equation checkpoint analysis were performed. The percentage of predictive error is presented. Results: ANOVA reveals that X2 plant does not have any significant impact on the response surface. The checkpoint batch showed the experimental value of CMDI and Disease activity index (DAI) as 1.33 and 0.66 respectively. It is worthwhile to note that the observed values were quite close to the calculated values of CMDI. A little difference in the value of DAI may be attributed to the inherent variation observed in animal studies. Conclusion: From this study, it was concluded that a dose of Aegle marmelos 100 mg/kg, a dose of Bombax malabericum 300 mg/kg, and a dose of Holarrhena antidysentrica 200 mg/kg will always be effective in IBD patients.

The spectrum of Cefditoren for Lower Respiratory Tract Infections (LRTIs) in Surabaya

Background: Empirical antibiotics among outpatients with Lower Respiratory Tract Infections (LRTIs) are scarcely allocated in Indonesia. The study aims to evaluate the pathogens causing LRTIs, drug sensitivity test and the minimum inhibitory concentrations of 90% (MIC90) of Cefditoren, Azithromycin, Amoxicillin-Clavulanic Acid, and Cefixime Methods: The study was performed in adult outpatients with LRTI that can be expectorated. Patients with diabetes mellitus, HIV, lung tuberculosis, renal or hepatic failure, and hemoptysis were excluded. We performed bacterial culture, antibiotic sensitivity, and MIC measurement of four antibiotics. Results: There were 126 patients with LRTIs, and 61 patients were eligible for the study. We identified 69 bacteria. We found Klebsiella pneumonia (n=16; 26.23%), Staphylococcus aureus (n=11; 18%), Pseudomonas aeruginosa (n=8; 13.11%), Acinetobacter baumanii complex (n= 4; 6.55%), Streptococcus pneumonia (n=3; 4.9%) and others bacteria as causa of LRTI. Testing MIC90 of Cefditoren and three empiric antibiotics on LRTI found that Cefditoren has a lower MIC of 90 for K. pneumonia (0.97(2.04) µg.mL-1) and S. pneumonia (0.06(0.00)µg.mL-1) than other antibiotics, but almost the same as Cefixime ((0.05(0.16)µg.mL-1) and (0.38(0.17)µg.mL-1). MIC90 Cefditoren for S.aureus (3.18(3.54)µg.mL-1) and P.aeruginosa (9.2(3.53)µg.mL-1) is lower than Cefixime but higher than Azithromycin and Amoxicillin-Clavulanic acid. Reference data MIC90 of Cefditoren for LRTI bacteria is lower than the other three oral empirical antibiotics. Conclusions: In vitro studies of an outpatient LRTI in Surabaya found gram-negative bacteria dominant. Cefditoren can inhibit K.pneumonia and S.pneumonia has lower MIC90 compared to other antibiotics. Cefditoren can inhibit gram-negative and positive bacteria causing LRTI.

Investigating the Effects of Aqueous and Alcoholic Extracts of Allium Hirtifolium and Allium Jesdianum on Keratinase Activity of Trichophyton Mentagrophytes

Background: Trichophyton spp., as pathogenic species to humans and animals, cause different forms of dermatophytosis through the production of particular enzymes, playing an essential role in tissue invasion. Among these, herein, keratinase was investigated, for the specific case of Trichophyton mentagrophytes, as a target of the effects of Allium hirtifolium and Allium jesdianum extracts, thus pharmacological potential of these plants was studied against keratinase activity. Methodology: Sampling was carried out on 20 bald patients from medical diagnostic laboratories and mycology centers, with suspected dermatophytosis of scalp. For confirming the presence of Trichophyton mentagrophytes in the specimens, different laboratory procedures were applied. Trichophyton mentagrophytes isolates were cultured on a screening medium containing keratin to verify production of the keratinase enzyme. The best enzyme-producing isolate was selected by measuring diameter of transparent halo around colony to be used in subsequent stages. Afterwards, the optimized conditions maximizing enzyme production and activity were determined. Finally, the inhibitory effect of different dilutions of aqueous and alcoholic extracts of Allium jesdianum and Allium hirtifolium on extracellular keratinase activity was studied. Results : Sixteen out of 20 fungal isolates were identified as the Trichophyton mentagrophytes. The most desirable reduction on keratinase activity was reported for dilution values of 50 and 100 mg/ml of both aqueous and ethanolic extracts of A.jesdianum, though much more significant decrease belonged to the latter, and for dilution values of 25 and 100 mg/ ml of both aqueous and ethanolic extracts of A.hirtifolium. Conclusion : Concerning our results, it is suggested that paying special attention to these natural compounds for the treatment of dermatophytosis could be remarkably effective, considering significant production of keratinase observed in T. mentagrophytes, and they are beneficial, as they have no side effects and offer an alternative to currently available medications, which are under the restriction of drug resistance.

Silibinin and Nano-Silibinin in Cuprizone Model of Multiple Sclerosis: Behavioral and Biochemical Investigation

Objectives: Multiple sclerosis (MS) is a long-lasting demyelinating inflammatory disease of the central nervous system (CNS). It has been shown that brain tissue in MS is exposed to oxidative stress during the disease period. Silymarin, a plant-derived flavonoid, can be extracted from Silybum marianum. The current experiment aimed to explore the effects of silibinin and especially nano-silibinin on neurobehavioral activity and biochemical antioxidant parameters in the cuprizone model of demyelination in mice for the first time. Methods: Demyelination was induced in mice by oral consumption of cuprizone 0.4%w/w for one week and then 0.2%w/w for four weeks. Treatment was performed with silibinin or nano-silibinin (70mg/kg body weight) for four weeks at the same time with cuprizone 0.2%w/w. After neurobehavioral tests (rotarod, tail flick, and open field), biochemical antioxidant parameters (glutathione level, superoxide dismutase activity, lipid peroxidation products, and total antioxidant capacity) were evaluated. Results: In this experiment, behavioral tests (rotarod and open field) displayed improvement in movement dysfunction using silibinin or nano-silibinin. Furthermore, silibinin and more efficiently nano-silibinin increased antioxidant parameters, such as superoxide dismutase (SOD) and glutathione (GSH) and total antioxidant capacity (TAC), and decreased lipid peroxidation. Conclusion: These data suggest that silibinin and nano-silibinin can improve movements in the cuprizone model of demyelination. Moreover, they may prevent cuprizone-induced oxidative stress. In conclusion, silibinin and more effectively, nano-silibinin, may exhibit therapeutic features in MS disease.

Preparation of Chitosan Particles as a Delivery System for Tetrahydrocurcumin: β-cyclodextrin Inclusive Compound for Colorectal Carcinoma

Background: Tetrahydrocurcumin is a hydrogenated active metabolite of curcumin that exhibits similar pharmacological effects to curcumin. However, its hydrophobic nature has limited its aqueous solubility and bioavailability. By incorporating the tetrahydro curcumin into β-cyclodextrin, its physiochemical property can be improved. Objective: To develop a chitosan composite loaded with tetrahydro curcumin inclusive complex, characterize the developed composites, and evaluate its effectiveness on cancer cells. Methods: Tetrahydrocurcumin was formulated into an inclusive complex with β-cyclodextrin in the ratio of 1:2 (Tetrahydrocurcumin: β-cyclodextrin). The tetrahydro curcumin inclusive complex loaded chitosan particles (THC IC-loaded CPs) were prepared using ionic gelation and later characterized using FTIR. Cytotoxicity of THC IC-loaded CPs in human colon cancer cells, Caco-2 cells, was examined using RTCA xCELLigence technology. The uptake of these particles by Caco-2 cells was also evaluated via fluorescing microscopy. Results: FTIR results confirmed the formation of the tetrahydrocurcumin inclusive complex and the loading of this complex into chitosan composites. The cytotoxic effect of THC IC-loaded CPs showed a dose-dependent relationship, and the IC50 found was 1.117mM and 0.959mM after 48 and 72 hours, respectively. THC IC-loaded CPs showed an immediate uptake by CaCo-2 cells, and the maximum uptake was observed after 1 hour of incubation. Conclusion: This study showed that THC IC-loaded CPs is a potential drug carrier to deliver tetrahydrocurcumin into cancer cells and able to produce a cytotoxic effect on cancer cells.

Synthesis and characterization of mesalamine silica nanoparticles

Background: Nanoparticles made of silica are new materials that can be used in a wide range of drug delivery methods because they are biocompatible and biodegradable. Mesalamine, a classic water-soluble medication, remains loaded into the synthesized silica nanoparticle and is considered for sustained release proficiency. Precipitation approach using high surface area and pore volume tetraethyl orthosilicate yielded mesalamine-loaded silica nanoparticles. Methods: The drug-loaded nanoparticle was created and produced using two different techniques. Fourier transform infrared spectrometry, differential scanning calorimetry, X-ray powder diffraction, Brauer Emmett teller, scanning electron microscopy, particle size measurements, and dissolution investigations have all been used to analyse the substance in some way or another. Results: Because of the high surface area, well-known results like the complete silica nanoparticle created using method-2 remained mesoporous. The onset peak of the method-2 formulation's DSC was 182.27°c, and the offset peak was 192.14°c, consistent with the DSC results. The particle size range varies from 205-225nm. The results demonstrate that the uptake of the mesalamine by burst release it for 30 minutes initial, followed by sustained maintenance of dose even after 240 minutes. The results indicate that the loading process has an effect on the extent of loading. When silica nanoparticles were impregnated with mesalamine, the amount of the drug contained was significantly higher than when they were wetted. Conclusion: In addition, the XRD results show that both the pure mesalamine and the formulation did not show any polymorphic deviation.

Repurposing of Neeri Ayurvedic tablet formulation against obesity: An in-vivo evaluation

Background : At present, 63 percent of women and 72 percent of men are obese. Obesity is a condition that causes increased rates of type 2 diabetes mellitus, heart disease, and arthritis, amongst other conditions. It was found that Neeri can control cholesterol and triglycerides levels which are associated with obesity. Therefore, Neeri has been assumed to treat obesity. Based on its efficacy to reduce cholesterol and triglycerides levels, it was assumed that it can be active against obese in-vivo. Methods : In-vivo studies were performed by utilizing albino Wistar rats (100–250g) approved and procured by IAEC resolution no. 2017/837/ac/MPH/12 from the animal house of the Institute of Foreign Trade and Management [IFTM] University, Moradabad, India. The Neeri was administered at different concentrations into five groups of obesity-induced albino Wistar rats, all the groups were treated for 42nd successive days accordingly and the in-vivo tests were performed on the 43rd day. Biochemical serum analysis was measured by ELISA assay. Results : Outcomes were expressed as Mean±SEM. The difference between experimental groups was compared by one-way analysis of variance (ANOVA) followed by Dennett’s test and was considered statistically significant when p<0.05. It was found a significant (p<0.05) decrease in total cholesterol triglycerides, low-density lipoprotein, and very high-density lipoprotein and along with increased high-density lipoprotein. Conclusion : Neeri can reduce body weight, cholesterol, triglycerides, low-density lipoprotein and very-low-density lipoprotein level, liver weight, heart weight, uterine fat, mesenteric fat, and kidneys weight level similar to the standard drug. It was concluded that Neeri Ayurvedic formulation can produce pharmacological action similar to the standard drug, Orlistat. In the future, further studies may proceed and Neeri tablets can be repurposed against obesity.

Solubility enhancement of glipizide and development of its fast-dissolving oral film

Background: Difficulty in swallowing tablet dosage form is common among all ages people, especially old and pediatrics. Fast dissolving oral films (FDOFs) may represent an innovative dosage type that settles the issue of gulping and supply fast onset of action. Objective: The objective of the present investigation was to increase the solubility of poorly soluble Glipizide (BCS Class II) by solid dispersion technique and develop its FDOFs. Methods: A solvent evaporation process was used to make a solid dispersion of the Glipizide. The saturation solubility of glipizide and its solid dispersion was determined in a different solvent. For the film preparation, solvent casting method was chosen. The excipients were selected based on pre-formulation data. The composition of the film was optimized based on a trial-and-error basis using different concentrations of plasticizer. The average weight, thickness, disintegration time, tensile strength, surface pH, folding endurance, drug content, and in-vitro dissolution analysis of the films were all taken into consideration. Results: There was no incompatibility between drug / solid dispersion and the excipients. The solid dispersion of the glipizide showed improved solubility by almost 10 folds. Many of the formulated films disintegrated in less than 30 seconds. At the end of 5 minutes, the optimized film had released more than 90% of the compound. The prepared films were found to be stable at room temperature. Conclusion: The solubility of Glipizide was improved successfully by solubilization technique using soluplus. The FDOFs of the glipizide were successfully formulated using pullulan as polymer.

Fixed Drug Eruptions Secondary to Fixed Drug Combination (ofloxacin/ornidazole): A Cross Sensitivity Case Report

Background: Fixed drug eruption (FDE) is an erythematous cutaneous patch caused by certain drugs through activation of immunologic reaction in the body. The onset of FDE is 30 minutes to 8 hours and is estimated to occur upto 16-21% of all cutaneous reactions. The irrational combination of fluoroquinolones and nitroimidazole is the most prescribed drug for diarrhea in India, and the drug is found to cause FDE either individually or in combination. Cross sensitivity is the major issue associated with Fluoroquinolones and nitroimidazole. Case repor: Our case is of a 45-year-old male who developed FDE due to a combination product of ofloxacin and ornidazole with past FDE history due to a combination product of norfloxacin and tinidazole. The patient presented with erythematous patches all over the body, swollen lips, mucosal erosion over the buccal cavity, and glans penis. Discussion: The patient was successively treated after the withdrawal of the culprit drug with oral Antihistamines, corticosteroids, and other topical creams and gels, which correlates with the standard management of FDE. Conclusion: Proper prescribing knowledge, documentation of drug allergies, and educating patient about allergic reaction play vital role to prevent future drug related problems.