PMC:7532132 / 6259-11576 JSONTXT

{"project":"2_test","denotations":[{"id":"33006710-16233912-28305","span":{"begin":238,"end":240},"obj":"16233912"},{"id":"33006710-17826969-28306","span":{"begin":2230,"end":2232},"obj":"17826969"}],"text":"MATERIALS AND METHODS\n\nMaterials\nIbuprofen sodium salt [\u003e 98%] purchased from Sigma-Aldrich, PVA [molecular weight (Mw) = 146,000–186,000 g/mol, 87–89% hydrolyzed] purchased from Sigma-Aldrich, and PHEA was synthesized in lab previously (32,33). Buffer tablets pH 6.8 and ethanol were purchased from Sigma-Aldrich.\n\nSample Preparation: Aqueous Solution\nAqueous solutions of PVA with a concentration of 5% w/v and 7.5% w/v were prepared by stirring PVA in distilled water using a magnetic stirrer. Distilled water was heated at a temperature of 90°C, and PVA granules were added and stirred for 2 h at 80°C. PHEA at a concentration of 2.5% w/v was added to already made PVA solutions and stirred for 12 h using a magnetic stirrer. Ibuprofen sodium at a level of 10% w/v was then added to PVA and PHEA solution and stirred for 2 h.\n\nSample Preparation of Pharmaceutical Films\nThe pharmaceutical films were prepared by casting 5 mL of the solution, described in “Sample Preparation: Aqueous Solution,” in a 60-mm plastic petri dish and placing petri dishes in a fume cupboard for 48 h to allow the solvent to evaporate. After 48 h, the film was dried and was subsequently peeled off gently from petri dish using forceps. Films were then cut into 1 cm × 1 cm square pieces. Films were produced according to the ratio reported in Table I.\nTable I Concentration of PVA, PHEA, and Ibuprofen Sodium Used to Prepare Pharmaceutical Films\nFilm PVA (% w/v) PHEA (% w/v) Ibuprofen sodium (% w/v)\nF1 5.0 – –\nF2 7.5 – –\nF3 5.0 2.5 –\nF4 7.5 2.5 –\nF5 5.0 2.5 10.0\nF6 7.5 2.5 10.0\nPVA polyvinyl alcohol, PHEA poly-N-hydroxyethyl-aspartamide\n\nScanning Electron Microscopy\nSEM studies were conducted on F5 and F6 films to analyze the morphology of particles and to calculate particle size. Images were collected on 1 cm × 1 cm film section using a Hitachi S5000 Field Emission Gun SEM with a tungsten tip. Before analysis, film samples were coated with 10 nm of gold. All images were taken using the secondary electron detector. ImageJ software was used to calculate the average particle size of drug particles by taking 100 measurements. Particle distribution index (PDI) was calculated accordingly with the following formula: (PDI) = \u003cd2\u003e / \u003cd \u003e2 (34).\n\nAttenuated Total Reflection Fourier Transform Infrared Spectroscopy\nFTIR analysis was conducted using a Perkin Elmer Frontier FTIR spectrometer to identify any interactions occurring between molecules, such as hydrogen bonding. Diamond ATR crystal was wiped clean with ethanol, and a background scan was carried out. The sample was then placed onto the crystal. The pressure was applied at a force gauge of 70. A total of 16 scans were taken at a resolution of 2 cm−1 and using a wavelength range of 4000–600 cm−1. Two replicates were carried out for each sample.\n\nDifferential Scanning Calorimetry\nDSC analysis was conducted using a DSC 2920 machine (TA instruments) to obtain melting temperature and determine whether materials are present in an amorphous or crystalline form. DSC analysis was conducted at a rate of 5°C/min, and samples were heated to 250°C. Nitrogen purge gas used had a flow rate of 130 mL/min. Samples were also held isothermally for 5 min. The sample was weighed and placed inside aluminum pans, and the lid was crimped to ensure it was securely closed. Pan was set in DSC instrument with an empty pan as a reference. Two replicates were carried out for each sample.\n\nDrug Content Studies\nUV analysis was used to produce a calibration curve of known concentrations of ibuprofen sodium. Absorbance values were measured using a Perkin Elmer Lambda 35 UV/VIS spectrometer. 0.05 g of ibuprofen sodium was weighed and dissolved in 100 mL of ethanol to form a stock solution, then diluted. A small volume of each solution was placed in a 4-mL quartz cuvette to measure absorbance values at a wavelength of 263 nm and obtain a calibration curve. Drug content was determined in 1 cm × 1 cm film samples that were weighed and dissolved in 10 mL of ethanol. Film samples with a weight of approximately 0.03 g were used. Samples were left in ethanol for 3 days, and the solution was then filtered through a 0.45-μm filter. Samples were then analyzed spectrophotometrically at 263 nm to determine drug content.\n\nIn Vitro Dissolution Studies\nDrug release from the film was investigated through dissolution studies; those were conducted using 100 mL of buffer pH 6.8 solution as a dissolution media. A paddle apparatus was used for this study, and dissolution media was heated to 37°C using a magnetic stirrer and stirred at 100 rpm. A 1 cm × 1 cm film section was weighed and placed in dissolution media. Film samples with a weight of approximately 0.03 g were used. At set time intervals, 10 mL was drawn out and replaced with 10 mL of same dissolution media at the same temperature. Time intervals used were 0, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 120, and 180 min. Solutions were then analyzed spectrophotometrically at 263 nm. Three replicates were carried out for dissolution of F5 and F6 films, and an average was calculated. Same dissolution method was used to carry out dissolution studies for ibuprofen sodium alone. Weight of ibuprofen sodium used was approximately 0.002 g. Statistical analysis was performed using two-way ANOVA to calculate the p value."}