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Background Candida biofilm is a major cause of denture stomatitis. We aimed to compare the efficacy of low-molecular-weight chitosan solutions against Candida albicans biofilm on polymethyl methacrylate (PMMA) resin. Methods Various types of chitosan were tested for anti-Candida activity by broth dilution. Two types were selected for further testing on 24-hour C.albicans biofilm formed on PMMA specimens. Specimens were randomly distributed among experimental groups, including 0.1% and 0.2% acetic acid, 3 and 6 mg/mL of oligomer chitosan and 30 kDa chitosan solutions, effervescent tablet (Polident), and 0.2% chlorhexidine, and immersed for 5 min to 12 h. The viability of C. albicans after cleansing were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Remaining viability was calculated into percentage relative to respective controls and analyzed using ANOVA with Tukey post-hoc tests. Live/dead fluorescence microscopy was also performed. Results Chitosan solutions had high efficacy against C. albicans biofilm on PMMA. The mean relative viability compared to control after 12-h immersion was 6.60 ± 4.75% and 12.72 ± 6.96% for 3 and 6 mg/mL oligomer, respectively, and 11.68 ± 4.81% and 18.08 ± 6.20% for 3 and 6 mg/mL 30 kDa chitosan, respectively. Conclusions Low-molecular-weight chitosan solution is an effective antifungal denture cleanser that can significantly reduce C. albicans viability in biofilm on PMMA.

Introduction Ambroxol is used in the treatment of acute and chronic respiratory conditions characterized by abnormal mucus secretion and impaired mucus transport and is available in a variety of formulations. This study aimed to compare the steady-state (SS) pharmacokinetic characteristics of extended-release (ER) 75-mg retard capsules with two immediate-release (IR) formulations (60-mg effervescent tablets and 30-mg tablets) over a 24-h period. Methods An open-label, randomized, three-period, six-sequence crossover study was conducted in healthy volunteers aged 18–45 years who had a normal body mass index. The test (ER 75-mg retard capsule once daily) and reference treatments (half of IR 60-mg effervescent tablet twice daily or 30-mg IR tablet twice daily) were administered on days 1–5 of each treatment period. Meals were standardized and concomitant therapy was prohibited. Blood samples for pharmacokinetic assessment were collected on day 5 (SS) of each treatment period. The co-primary endpoints were exposure (AUCSS 0–24) and maximum plasma level (Cmax SS). Results Twenty-four participants received ambroxol (male n = 13, 54.2%; mean ± standard deviation [SD] age 25.0 ± 6.4 years) and 23 completed the study. ER retard capsules provided similar AUCSS 0–24 compared to IR tablets (geometric means ratio [GMR] 110.7%; 90% confidence interval [CI] 99.8%, 122.7%) and effervescent tablets (GMR 106.9%; 90% CI 100.3%, 114.0%). ER retard capsules provided similar Cmax SS compared to IR tablets (GMR 84.7%, 90% CI 77.0%, 93.3%), and lower Cmax SS compared to effervescent tablets (GMR 80.9%, 90% CI 73.9%, 88.6%). Time to Cmax SS (tmax SS) was longer with ER retard capsules (6.0 h) than with IR tablets (2.0 h) or effervescent tablets (1.0 h). Conclusions ER ambroxol 75-mg retard capsules given once daily showed a similar pharmacokinetic profile to IR ambroxol formulations and therefore can be used instead of these in the treatment of respiratory conditions. ClinicalTrials.gov identifier NCT02036775. Electronic supplementary material The online version of this article (10.1007/s41030-020-00116-7) contains supplementary material, which is available to authorized users., Plain Language Summary Ambroxol is used to relieve the symptoms of respiratory conditions in which abnormal mucus secretion is a problem, including the common cold, acute and chronic bronchitis, and chronic obstructive pulmonary disease. Different formulations of ambroxol are available, including tablets and effervescent tablets that release the drug as soon as they are digested, but need to be taken twice a day, or extended release (retard) capsules that release the drug slowly over 24 h and can be taken once a day. This randomized, three-period, six-sequence crossover study in 24 healthy volunteers compared the pharmacokinetics of three formulations of ambroxol: tablets, effervescent tablets, and retard capsules. The amount of drug in the bloodstream over 24 h was similar with all three formulations, but (as expected) the time to reach peak plasma concentration was longer with the retard capsules than both forms of tablet. These results show that people who take ambroxol for respiratory conditions will receive the same amount of ambroxol whether they take retard capsules, standard tablets, or effervescent tablets. Electronic supplementary material The online version of this article (10.1007/s41030-020-00116-7) contains supplementary material, which is available to authorized users.

In this work, an effervescent tablet containing ionic liquids was made and used in ultrasonic-assisted dispersive liquid–liquid microextraction for extraction and preconcentration of benzoylurea in...

Tableting of fruit powders is gaining popularity because of the advantages it brings in, such as ease of storage, transportation, and use, and effervescent tablets could be a good alternative to accomplish fast dissolving. The present study provides a specific effervescent tablet formulation that is appropriate for the delivery of mango, cactus, and Chlorella fruit powder. The direct compression method was employed. A series of disintegration time, tensile strength, and moisture content tests were performed on the different formulations at each stage. The effects of effervescent agents' ratio, fruit powder proportion, acid and alkali content, and mannitol and lactose content on tablet properties were investigated. The results indicated that the tablet properties were highly influenced by formulation, especially the ratios of effervescent agents, fruit powders, acid to alkali ratio, as well as mannitol to lactose ratio. The best performing formulation was as follows, 45% effervescent agents (citric acid monohydrate:sodium bicarbonate = 1.3:1), 35% adhesives (mannitol:lactose = 1:8), and 20% mixed fruit powders (mango:cactus:Chlorella fruit powders = 14:5:1). With this formula, the moisture content was 3.62% and the disintegration time was 154 s, as well as a sufficient tensile strength of 2.32 MPa. Our study presented useful findings regarding the specific effects of changing ingredient ratios on tablet strength and other properties and provided a basis for the potential of using mango, cactus and microalgae powders as novel functional ingredients for fruit powder effervescent tablets. This may be used as a basis for further research on tableting.

Ibuprofen is an analgesics-anti-inflammatory agent that is often prescribed, but it has gastrointestinal side effects. Effervescent tablet is expected to resolve that problem, but Ibuprofen has a low solubility in water. So it modified into a solid dispersion using Polyethylene-glycol 6000 as hydrophilic polymer to improved solubility in water. Direct compression method is suitable for solid dispersion, so it needs co-processed excipient. Starches were made by extracting Suweg tuber. Combination of Suweg starch and lactose are developed as co-processed excipient by Simplex Lattice Design method. Ibuprofen-PEG 6000 is formulated with variation of ratio 1:1, 1:1.5, 1:2, 1:3, and 2:1. Optimum ratio was confirmed by yield (%), solubility, drug content, FTIR profile, and SEM. Software Design Expert produce 8 formulas based on lower and upper value of Suweg starch and lactose ratio, with physical responses are hardness, friability and dissolving time. Optimum combination of co-processed excipient was confirmed by statistical analysis of one sample t- test based on physical responses compare to software prediction. Optimum ratio of ibuprofen-PEG 6000 is 1:1. FTIR analysis drug excipient compatibility showed no interaction with polymer and excipients. SEM analysis showed change of particle structure with highest solubility of solid dispersion is 0.37 mg/mL, drug content 99.16%, and yield 96.70%. Optimum proportion of Suweg starch: lactose are 64.32% : 35.68%. Optimum Formula of Effervescent Tablet meets good tablet quality standard and stability, there are : granular flow rate 4.7 6± 0.29 g/sec; angle of response 27.52 ± 0.95 °; dissolving time 211.67 ± 18.88 sec; hardness 2.11 ± 0.05 Kg; friability 0.47 ± 0.04%; pH 6.07 ± 0.02, moisture content 0.41 ± 0.2, and percentage of ibuprofen in tablet 98.54 ± 0.42%.

The present study is targeted to formulate and prepare effervescent tablets of Glipizide to provide more elegancy, comfortability, and improved pharmacokinetics in diabetic treatment than the conventional dosage. Three formulations (F1, F2, and F3) of the effervescent tablet of Glipizide (5mg) were formulated with different amounts and ratios of excipients. By wet granulation technique, 60 tablets for every formulation were prepared with a weight of 700mg per tablet. Then, the features of both granules and tablets were evaluated by published methods. The angle of repose, Hausner ratio, Carr's index, Loss on drying (LOD), and Moisture Content (MC) used to measure granules property successfully proved right follow ability and compressibility. In contrast, physical and drug content related investigation failed to determine the perfectness of all three formulations. Friability on the formulations was around 0.70%, indicating the expected USP limit of friability (0.5 to 1%). The mean disintegration time of the formulations was from 95s to 105s. The tablet potency assay found 95.20% for F1, 88.80% for F2, and 97.40% for F3. The dissolution pattern of the drug followed a linear relationship with time. After one and a half hours, the highest amount of 59.20% cumulative dissolution was determined for F3 that revealed its strategic improvement of the drug solubility. As Glipizide is a poorly water-soluble drug, the effervescent tablet might mitigate disintegration and dissolution-related limitations and, consequently, enhance the drug's bioavailability.

A novel approach using magnetic Fe3O4 @ porous activated carbon effervescent tablet-assisted deep eutectic solvent-based dispersive liquid–liquid microextraction (META-DES-DLLME) combined with HPLC was developed for the measurement of phenolic endocrine disrupting chemicals (bisphenol A, p-tert-octylphenol, nonylphenol) in environmental water. In the proposed method, deep eutectic solvents synthesized by 1-dodecanol and hexyltrimethylammonium bromide were applied as extraction solvent. A magnetic effervescent tablet, containing a foaming agent and a new magnetic material, combined the dispersion of the extraction solvent and the magnetic recovery into one step. The influence of parameters, including the composition and volume of DESs, the type and amount of acid, the amount of sodium bicarbonate, the composition and amount of Fe3O4 @ porous activated carbon, the pH, and the amount of sodium chloride, were optimized. Under the optimized conditions, accuracy and precision were demonstrated over the whole concentration range of 10–1000 μg L-1. The extraction recovery ranged from 81.0 to 94.7% with a relative standard deviation of 1.2–6.7%, and the LOD and LOQ ranged from 0.82 to 1.7 μg L-1 and 2.7–5.5 μg L-1, respectively. The method was successfully applied to extract and analyse the phenolic endocrine disrupting chemicals in environmental water.

This research is a formulation of the drug as an effervescent tablet by two methods (direct compression and wet granulation). The bitter taste was masked by saccharine as sweeting agent but by little concentration in compared to previous effervescent formula, furthermore the effervescent effect of citric acid, tartaric acid and sodium bicarbonate lead to improve the taste of the drug. Also the Guar was used as binder agent lead to hide the taste in higher concentration with tragacanthgum as mixture to improve rheological properties beside sustained release in compared to previous effervescent formula to enhance its therapeutics efficacy. The vanillin which was used as flavoring agent also enhances the palatability with more amount to previous formula. The formulated tablets were passed all the fundamental testes in the monograph, and also microbiological sensitivity test was done against (Escherichia coli, Salmonella typhi, Salmonella paratyphi and Staphylococcus aureus) and then the results were compared to select the suitable one. Also compression was done between two formula of wet granulation method (the binder increase concentration and die cavity when was change).This study was found that formulating the drug as effervescent tablet by wet granulation method (with more binder of rheological gum less saccharin) concentration and die cavity No thirteen or twenty is the more better than previous effervescent ciprofloxacin formula.

A novel and automated, stability-indicating, reversed phase ultra performance liquid chromatography (UPLC) method was developed and validated for the quantitative determination of erdosteine, its known impurities and two novel degradation products in a new pharmaceutical dosage form (effervescent tablets). The chromatographic separations were performed on a Waters Acquity UPLC HSS T3, 1.8µm (2.1mm × 150mm, I.D.) stainless steel column. The mobile phase consisted of 0.1% TFA in water and methanol under gradient elution conditions, at a flow rate of 0.29mL/min, for the assay and impurities analysis. UV detection was set at a wavelength of 238nm. Erdosteine raw material, placebo and effervescent tablets were subjected to forced degradation. The new degradation products (labeled OX1 and OX2) were found after oxidative treatment and characterized by ultra performance liquid chromatography mass spectrometry. The validation parameters such as linearity, limit of detection (LOD) and quantification (LOQ), accuracy, precision, specificity and robustness were highly satisfactory for all analyzed compounds. LOD (0.020 and 0.011–0.385µg/mL for erdosteine and impurities, respectively) and LOQ values show the high sensibility of the method. Specificity of the method was confirmed by testing the matrix components. The validated method demonstrated to be suitable for routine quality control purposes and for routine stability studies of erdosteine in effervescent formulations.

Risperidone is a poorly water soluble atypical antipsychotic drug. This work investigated the potential of developing risperidone effervescent tablets to facilitate drug administration and mask drug taste. The solid dispersion technique was selected to improve drug solubility due to its ease of scaling up, reproducibility and affordable cost. Thirty formulas were prepared adopting a 5(1).2(1).3(1) full factorial design. Trehalose, Inulin, pregelatinized starch, carboxymethylcellulose sodium and Eudragit E100 were used as hydrophilic carriers at different ratios. Rotovap, lyophilization and the kneading-oven were applied as solvent evaporation techniques. Differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy showed that the drug was present as amorphous material entrapped within the carrier matrix. Eight tablet blends were prepared using different effervescent mixture ratios with or without binder and lubricant/glidant mixture. All of the blends had acceptable flowability, acceptable effervescence times and immediate drug release that could not be achieved by any of the control formulas. The formula of choice contained 40% effervescent mixture, 5% starch, 1% boric acid, 1% aspartame and sufficient lactose. The relative bioavailability (RB) of risperidone from this formula was 161.41% with a significantly higher extent of absorption compared to the market conventional tablets. This formula may be promising in improving patient compliance and drug efficiency.

Background Tramadol/paracetamol is a fixed-dose combination prescribed for the relief of moderate to severe pain. The combination acts synergistically and guarantees the rapid onset of paracetamol and the prolonged analgesic effect of tramadol with good tolerability. These drugs are often used in various formulations in the treatment of patients with postoperative pain, e.g. after stomach resection. Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect the process of drug absorption. The aim of the research was an analysis of the pharmacokinetics of tramadol/paracetamol from effervescent and conventional tablets in patients after total gastrectomy. Methods The research was carried out on patients after gastrectomy with Roux-en-Y reconstruction. The patients received two tramadol/paracetamol fixed-dose combination tablets in a single orally administered dose of 75/650 mg (2 × 37.5/325 mg). The patients were subjected to one of the two study drug group with: I. effervescent tablet (ET) ( n = 14; mean [SD] age, 63.4 [10.1] years; weight, 75.5 [15.3] kg; and BMI, 26.0 [4.6] kg/m 2 ) and II. conventional tablet (CT) ( n = 12; mean [SD] age, 66.8 [7.7] years; weight, 79.8 [17.8] kg; and BMI, 27.4 [5.3] kg/m 2 ). Blood samples were collected within 10 h after the drug administration. The plasma concentrations of tramadol and paracetamol were measured with validated HPLC (high-performance liquid chromatography) method with UV detection. Results The comparison of the paracetamol and tramadol C max ratio for the ET group with that of the CT group gave ratios of 1.16 [90% confidence interval (CI) 1.06, 1.27] and 0.86 (90% CI 0.72, 1.02), respectively. The comparison of the paracetamol and tramadol AUC 0– t ratio for the ET group with that of the CT group showed ratios of 0.99 (90% CI 0.88, 1.10) and 1.00 (90% CI 0.82, 1.22), respectively. The comparison of the difference for the effervescent and conventional formulation gave an estimated decrease in t max of 0.5 h for paracetamol and 0.13 h for tramadol. Conclusions In view of the changes in the pharmacokinetics of paracetamol and tramadol in the patients after gastric resection for both formulations compared the conventional tablet seems to be more appropriate due to the comparable rate of absorption of both substances, higher concentrations of tramadol and comparable exposure to paracetamol.

A simple and sensitive procedure was proposed for spectrophotometric determination of ascorbic acid. It was found that the reduction of Ag+ to silver nanoparticles (Ag-NPs) by ascorbic acid in the presence of polyvinylpyrrolidone (PVP) as a stabilizing agent produce very intense surface plasmon resonance peak of Ag-NPs. The plasmon absorbance of the Ag-NPs at λ = 440 nm allows the quantitative spectrophotometric detection of the ascorbic acid. The calibration curve was linear with concentration of ascorbic acid in the range of 0.5–60 μM. The detection limit was obtained as 0.08 μM. The influence of potential interfering substances on the determination of ascorbic acid was studied. The proposed method was successfully applied for the determination of ascorbic acid in some powdered drink mixtures, commercial orange juice, natural orange juice, vitamin C injection, effervescent tablet, and multivitamin tablet.

Medications are often crushed and mixed with foods or fluids to aid drug delivery for those who cannot or prefer not to swallow whole tablets or capsules. Dysphagic patients have the added problem of being unable to safely swallow fluids, so thickeners are added to ensure safe swallowing. These thickened fluids are then also used to deliver crushed medications in replacement of water. This thesis explores the influence of thickened water co-administration on drug release in gastric fluid, the effect of rheological properties of these agents and their contribution to describing the mechanism of release. The literature review (Chapter 1) examines oral dosage form administration, rheological properties of these agents as a means to ensure medication delivery and mechanisms of drug release. It is highlighted that thickened fluids have the potential to alter drug release but prediction of the effect of co-administration is not currently reported. Chapter 2 investigates the delivery of medications with thickened fluids as an indicator for potential compromise of drug bioavailability. In vitro dissolution in simulated gastric fluid is investigated for crushed atenolol immediate release tablets mixed with thickened fluids. Five commercial viscosity-increasing agents of varied polysaccharide composition are used at three thickness levels prescribed for dysphagic patients (levels 150, 400, 900). All types of thickening agents are non-Newtonian shear thinning fluids. The greatest thickness (level 900) significantly restricts dissolution, and products that are primarily based on xanthan gum also significantly delay dissolution at the intermediate thickness level (level 400). The interactions of the polysaccharide chains, particularly the rigid rod type conformation of xanthan gum, traps drug molecules within it resulting in impaired dissolution. Under the conditions of this experiment, the higher concentrations of thickening agents remain in large lumps rather than disintegrating into the media. Drug release is generally affected to a greater extent by high-viscosity fluids than low-viscosity fluids at 50 s-1, but viscosity at this single shear rate of 50 s-1 is not a good indicator for effect on drug dissolution because viscosity changes with shear rate. The determination of other rheological parameters such as viscoelasticity and the effect of breaking up of the structures may be required. To investigate whether it is possible to improve drug release from thickened fluids, in Chapter 3 the effect of the state of aggregation of the active ingredient with thickened fluids is investigated. Paracetamol is the model drug because it is available in a range of formulations with the drug in solution (elixir, dissolved effervescent tablet) or dispersion (suspension). Xanthan gum, which causes the greatest restriction on dissolution (Chapter 2), is used at level 900 as the thickener. Crushed tablets with thickener are prepared using manual (i.e. the standard method in clinical practice) or mechanical mixing. The unthickened elixir and suspension exhibit different dissolution profiles (100% and 34% at 30 min, respectively), but once thickened they are very similar (12% and 14% at 30 min, respectively). The dissolved effervescent tablet has a very similar dissolution profile to the crushed tablets once it is thickened to level 900. Incorporation of the crushed tablets with thickener using an overhead stirrer causes a significant reduction in dissolution (27% at 30 min) compared to manual mixing using a spatula (36%). Thickened products are weak gels with high zero-shear viscosity, and the presence of apparent yield stress in combination with high G’ values compared to G” (viscoelasticity) impact drug release. The restriction on drug release is not influenced by the theoretical state of the drug (dissolved or dispersed), and the approach typically used in clinical practice cannot be improved by altering the order of incorporation or mixing method. Chapter 4 aims to consider the kinetics of drug diffusion through the thickened fluid in the absence of hydrodynamic effects. It is hypothesed that drug diffusion decreases as concentration of polysaccharide increases within the thickened system, rheology determines drug diffusion and drug release increases when the diffusion pathway is reduced. These postulates are studied using a vertical diffusion cell, rheology (viscoelasticity) and drug release from various drop sizes of thickened water. Diffusion of atenolol, not dissolution, controls the rate of its release from solutions of xanthan gum and guar gum and depends on the concentration of the gums in solution which relates to the polysaccharide chain entanglement and rheology. After concentration increases to a certain level, diffusion coefficient no longer reduces and rheological parameters are not good predictors of diffusivity. Reducing droplet size results in an improvement in drug release rate, indicating that shear forces within the gastrointestinal tract that cause thickened fluid droplets to break up are expected to increase drug release. In conclusion (Chapter 5), drug release from thickened water, used to aid delivery of medications, is restricted by the polysaccharide structure and break-up forces acting on it. This restriction is drug-dependent and likely to be affected by tablet excipients, and requires further consideration. Delivery of crushed medications in an alternative fluid would be advisable, for example an agent that changes its conformation in response to applied forces or the acidic environment that are typical of the stomach. Ultimately, assessment of in vivo drug release and absorption from crushed tablets delivered in thickened fluids is required for correlation with the in vitro data presented here.

Application of Quantifying Scoring Systems for the Determination of Changes of the Mucosa of the Upper Gastrointestinal Tract / A comparative study of a diclofenac effervescent tablet with conventional diclofenac preparations and acetylsalicylic acid after repeated administration Background and aim: A new diclofenac effervescent tablet (DIC-BT) was developed in order to circumvent the high variable delay in delivery of the drug in enteric coated tablets of diclofenac (CAS 15307-86-5). The gastrointestinal side effects of the effervescent tablet were investigated in comparison to two other galenic principles of DIC preparations (DIC entero coated dragees = DIC-mrD) and dispersible tablets (DIC-DispT) and to acetylic salicylic acid (ASA (CAS 50-78-2). For the assessment of gastrointestinal side effects, two score systems were used simultaneously. The Lanza-scores were compared with our HEU-criteria system (Haemorrhage, Erosion, Ulceration) to find out if the pattern and the localisation of the lesions differ between the drugs tested. Methods: In a single-blind, randomised, controlled, parallel study design healthy volunteers (27 females, 33 males; mean age 26.9 years, mean b.w. 72.5 kg, Helicobacter pylori antibody negative) were treated by 150 mg/d DIC or 1500 mg ASA (as positive control group) for 7 days. DIC-BT (n = 20 subjects), DIC enteric coated dragees (DIC-mrD) (n = 20), DIC-Dispers tablets (DIC-DispT) (n = 10) and ASA (n = 10) were administered t.i.d. The effects were investigated by videoendoscopy with chromoscopy before and after treatment. Mucosa lesions were assessed according to the Lanza-scores and HEU-criteria system. The results were calculated as pre-post comparison and assessed as paired test between treatment groups. Results: DIC preparations caused mostly erosions and scarcely haemorrhages, but different from ASA only few combined lesions of haemorrhages and lesions in Corpus ventriculi and Bulbus duodeni. The number of mucosal lesions was different with regard to the region (Antrum ventriculi > Corpus ventriculi > Bulbus duodeni). The spreeding with Helicobacter pylori (histological assessment at the end of study) varied between 20 % and 50 % (7/20 subjects in DIC-BT and DIC-msrD, respectively, 5/10 in DIC-dispT group, 2/10 subjects in the ASA group). Based on the HEU-criteria, erosions were seen in 9/20 subjects in DIC-BT, 10/20 subjects in DIC-mrD, 4/10 in DIC-DispT, and 3/10 subjects in ASA group, respectively, the combination of haemorrhages and erosions is seen in 2/ 20 subjects in DIC-BT, 6/20 in DIC-mrD, 4/10 subjects in DIC-DispT, and in 7/10 subjects in the ASA group, respectively. The difference is significantly between DIC-BT and ASA (p 2), (a) erosions were seen in 7/20 subjects in DIC-BT, 15/ 20 subjects in DIC-mrD, 7/10 in DIC-DispT, and 9/10 subjects in ASA group; (b) haemorrhages were seen in 0/20 subjects in DIC-BT, 5/20 subjects in DIC-mrD, 2/10 in DIC-DispT, and 4/10 subjects in ASA group, (c) combined type in 3/20 subjects in DIC-BT, 8/20 subjects in DIC-mrD, 5/10 in DIC-DispT, and 8/10 subjects in ASA group, respectively. Independent of the scoring systems, the difference was significant between DIC-BT and DIC-mrD, as well as between all DIC preparations and ASA At the end of the study Helicobacter pylori infections were observed by biopsy in 20–50 % of volunteers (DIC-BT and DIC-mrD in 7/20 subjects, each, and DIC-DispT in 5/10, and ASA in 2/10 subjects, respectively) and between Dic-BT and ASA (p Conclusion: Mucosal lesions induced by DIC-BT were significantly less than by DIC-mrD and DIC-DispT. The effect was confirmed by both scoring systems, i.e. Lanza scores and HEU-criteria system. Using the HEU-criteria the pattern and the localization of the lesions could be characterized. There were remarkable differences between the effects of DIC and ASA. The assessment of gastrointestinal side effects using the HEU-criteria was superior to Lanza-scores because there was no bias according to the type of lesion and the type of drug.

A rapid and simple method based on capillary electrophoresis was developed for the quality control of nutraceuticals containing resveratrol. Setting the UV detector at 280 nm, the optimisation involved the separation of 11 effervescent tablet components, including the active compounds vitamin C, vitamin B 2 , flavanones and hydroxycinnamic acids. Flufenamic acid was employed as internal standard. The effects of background electrolyte concentration, acetonitrile percentage and voltage were investigated by means of response surface methodology, considering as responses the critical resolution values and analysis time. The optimum conditions were found by Derringer desirability function. The background electrolyte consisted of 23 mM borate buffer, adjusted to pH 10.0 with 1 M sodium hydroxide, containing 7% (v/v) acetonitrile. Temperature and voltage were set at 25 °C and 26 kV, respectively. Applying these conditions, the analysis time was below 7 min. The performances of the method were tested in terms of selectivity, robustness, linearity and range, accuracy and precision and system suitability, following ICH guidelines.

Objectives.To characterize the pharmacokinetic profile of levodopa (L-dopa) and carbidopa after repeated doses of the effervescent tablet of melevodopa/carbidopa (V1512; Sirio) compared with standard-release L-dopa/carbidopa in patients with fluctuating Parkinson’s disease. Few studies assessed the pharmacokinetics of carbidopa to date.Methods.This was a single-centre, randomized, double-blind, double-dummy, two-period crossover study. Patients received V1512 (melevodopa 100 mg/carbidopa 25 mg) or L-dopa 100 mg/carbidopa 25 mg, 7 doses over 24 hours (Cohort 1), 4 doses over 12 hours (Cohort 2), or 2 doses over 12 hours in combination with entacapone 200 mg (Cohort 3). Pharmacokinetic parameters included area under the plasma-concentration time curve (AUC), maximum plasma concentration (Cmax), and time toCmax(tmax).Results.Twenty-five patients received at least one dose of study medication. L-dopa absorption tended to be quicker and pharmacokinetic parameters less variable after V1512 versus L-dopa/carbidopa, both over time and between patients. Accumulation of L-dopa in plasma was less noticeable with V1512. Carbidopa exposure and interpatient variability was lower when V1512 or L-dopa/carbidopa was given in combination with entacapone. Both treatments were well tolerated.Conclusions.V1512 provides a more reliable L-dopa pharmacokinetic profile versus standard-release L-dopa/carbidopa, with less drug accumulation and less variability. This trial is registered with ClinicalTrials.govNCT00491998.

Objective To investigate the efficacy and safety of two different budesonide formulations (effervescent tablet for orodispersible use (BET) and viscous suspension (BVS)) with different daily dosages for short-term treatment of eosinophilic oesophagitis (EoE). Design Adults with active EoE (n=76) randomly received 14 days’ treatment with either BET 2×1 mg/day (BET1, n=19) or BET 2×2 mg/day (BET2, n=19), or BVS 2×5 mL (0.4 mg/mL)/day (BVS, n=19) or placebo (n=19) in a double-blind, double-dummy fashion, with a 2-week follow-up. Primary end point was histological remission (mean of

A drug delivery system(DDS) for practically insoluble meloxicam was developed and evaluated by dissolution study. A novel DDS is two layered system, where the first layer is consisted of gas-forming agent for an immediate release and the second layer is composed of metolose SR(HPMC) for sustained release. This bilayered tablets were manufactured by using manual single punch machine. The results of dissolution study showed an initial burst release followed by sustained release for the experimental period time. From a pharmaceutical point of view, the designed DDS for meloxicam would be informative system in terms of poorly soluble analgesic medicines.

Near-infrared spectroscopy (NIRS) was used to determine acetylsalicylic acid (ASA) in three different effervescent tablet formulations. The nominal ASA concentrations were 14.9% in the single substance formulation (ASA Mono), 17.4% in the combination with ascorbic acid (ASA + C) and 8.7% in the combination with paracetamol and ascorbic acid (ASA Combi). In each case the tablet matrix was composed of seven excipients typical of effervescent tablets. All three formulations were measured as intact tablets in diffuse transmittance and reflectance and as powdered tablets in diffuse reflectance. Calibration was carried out by partial least square (PLS) regression of second derivative spectra. High-performance liquid chromatography (HPLC) was used as the reference method. The relative standard errors of calibration (RSEC) achieved for the three NIR methods were between 1.20 and 2.01% for ASA Mono, between 1.91 and 2.21% for ASA + C and between 2.41 and 4.50% for ASA Combi. The results obtained in transmittance mode were comparable with those obtained in reflectance mode, which is normally used in NIRS. In the test sets of ASA Mono and ASA + C relative root mean square (RRMS) values between 2.21 and 3.13% were obtained. The three NIR methods applied are thus suitable for the quantitative determination of ASA in effervescent tablets and have the advantage over HPLC of being rapid and simply carried out with little sample preparation; they are nondestructive and do not require any environmentally harmful reagents.

A rotatable central composite design is used to evaluate the effects of lubricants and compression force on the physical characteristics of effervescent tablets. Effervescent tablets lubricated with a combination of spray dried L-leucine and polyethylene glycol 6000 are prepared by direct compression and examined. Residual force, crushing strength and disintegration time are considered as response variables and related to the L-leucine and polyethylene glycol concentrations and to the compression force. The calculated models are used to assess the influence of the production factors on tablet properties. As increasing amounts of L-leucine, showing good lubricating properties, reduce the crushing strength and prolong tablet disintegration, the L-leucine concentration is kept at a low level. An optimum tablet formulation contains 2% L-leucine and 3% polyethylene glycol 6000. The tablets have a tensile strength of 0.47 MPa and disintegrate in less than 2 min. Predicted and experimental results are in agreement within a 95% CI.

Purpose: The present investigation is aimed at comparing the pharmacokinetic profile (Bioavailability) of aspirin in tablet formulations, which were prepared by using different effervescent excipients such as citric acid and malonic acid. Materials and Methods: The relative bioavailability and pharmacokinetics of citric acid based aspirin effervescent tablet (Product A) and malonic acid based aspirin effervescent tablet (Product B) formulations were evaluated for an in-vitro dissolution study and in-vivo bioavailability study, in 10 normal healthy rabbits. The study utilized a randomized, crossover design with a one-week washout period between doses. Blood samples were collected at 0, 1, 2, 4, 6, 8, 12 and 24 hours following a 100 mg/kg dose. Plasma samples were assayed by High Performance Liquid Chromatography. T max , C max , AUC 0-24 , AUC 0- ∞, MRT, K a, and relative bioavailability were estimated using the traditional pharmacokinetic methods and were compared by using the paired t-test. Result: In the present study, Products A and B showed their T max , C max , AUC 0-24 , AUC 0- ∞, MRT, and K a values as 2.5 h, 2589 ± 54.79 ng/ml, 9623 ± 112.87 ng.h/ml, 9586 ± 126.22 ng.h/ml, 3.6 ± 0.10 h, and 0.3698 ± 0.003 h -1 for Product A and 3.0 h, 2054 ± 55.79 ng/ml, 9637 ± 132.87 ng.h/ml, 9870 ± 129.22 ng.h/ml, 4.76 ± 0.10 h, and 0.3812 ± 0.002 h -1 for Product B, respectively. Conclusion: The results of the paired t-test of pharmacokinetics data showed that there was no significant difference between Products A and B. From both the in vitro dissolution studies and in vivo bioavailability studies it was concluded that products A and B had similar bioavailability.

A comparison of the bioavailability of disulfiram (DSF) after administration of non-effervescent Antabuse tablets (CP Pharmaceuticals, UK) and Antabuse effervescent tablets Antabuse (A/S Dumex, DK) has been made in two cross-over studies. The first study included 6 volunteers who were given 400 mg DSF after an overnight fast. The bioavailability of DSF after administration of non-effervescent was found to be only 27% of that achieved with effervescent tablets. The second study included 24 volunteers who were given 800 mg DSF after a light standardized meal. The relative bioavailability of DSF after administration of non-effervescent compared with effervescent tablets was found to be only 34%. In addition to the difference in bioavailability of DSF after administration of the two preparations, a considerable difference was seen between the two studies. A light meal seems both to increase the bioavailability of DSF and to reduce the interindividual variation. A two to threefold increase in the bioavailability of DSF was found. Thus, the bioavailability of DSF appears to depend on both the formulation (preparation) and the mode of administration. A lack of bioequivalence between the two investigated DSF preparations was found.

The pharmacokinetics of two 200 mg ibuprofen (IP) film-coated tablets and a 200 mg effervescent tablet were studied in cross-over fashion on 14 healthy volunteers. After ingestion of the novel film-coated tablet, absorption half life (0.6 h) was 42-50 % (p

Beclamide was microencapsulated in order to mask the taste, by a simple coacervation method using gelatin. Anhydrated sodium sulphate was used as coacervating agent. Glutaraldehyde, glutaraldehyde:isopropanol (8 : 32) and formaldehyde:isopropanol (8 : 32) were used as hardening agents. The optimum microencapsulation conditions were: 44 g water, 9 g beclamide and 47 g sodium sulphate as components at a temperature of 40 + 0.5 degrees C with glutaraldehyde (25 per cent w/v) as hardening agent. The dissolution rate of beclamide from prepared microcapsules was determined by a rotating basket and the dissolution kinetics were investigated according to the zero-order, Hixson-Crowell and Higuchi equations. The dissolution pattern of beclamide was first-order kinetic. Release rate constants, t50%, t90% and AUC values were calculated. All these values were discussed for differently obtained microcapsules. Beclamide was formulated in conventional, chewable and effervescent tablet forms. Physical tests were applied to all tablets. The paddle method was used as an in vitro dissolution test method for evaluation of conventional tablets.

The primary objective of this study was to compare the lubrication properties of micronized poloxamer 188 (Lmicrotrol micro 68) and micronized poloxamer 407 (Lmicrotrol micro 127) with certain conventional lubricants such as magnesium stearate and stearic acid. The secondary objective was to use these micronized poloxamers as water-soluble tablet lubricants in preparation of effervecsent tablets. The results showed that these micronized poloxamers have superior lubrication properties compared with stearic acid, with no negative effect on tablet hardness, friability, disintegration, or dissolution. Moreover, lubricant mixing time had no significant effect on tablet properties when poloxamers were used as lubricants. Effervescent tablets also were produced successfully using micronized poloxamers as lubricants. The micronized poloxamers had a better lubrication effect in comparison with that of water-soluble lubricant l-leucine.

Bioadhesive tablet formulations of ketoconazole for vaginal delivery were studied. Carbomer (Carbopol 974P, Carbopol 934P), hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) were used as candidate bioadhesive polymers. Effervescent was incorporated into the formulations as a disintegration agent. The swelling behavior and bioadhesive strength of the drug-free tablets were investigated. Carbopol 934P was selected as biopolymer in combination with HPMC or HPC at different ratios to develop five drug-loaded formulations. The swellings, tackiness and in vitro release were studied on the tablets. A good sustained effect and a moderate bioadhesion were obtained with the tablets. The formulation containing 100 mg of effervescent, with the Carbopol 934P:HPC ratio of 1:9, seemed to be the optimum one for the tablet. In vivo drug residence tests were carried out by administering the preferred formulation to female rats. The results showed that the drug remaining followed a one-order model. Even after 24 h of administration in vagina of rats, 17% of the original employed drug was retained on the vaginal tissue. Our study may provide a potential vaginal tablet formulation of ketoconazole against Candida albicans.

The oral solid dosage forms are the most popular way of taking medication despite having some disadvantages like slow absorption and hence prolong onset of action. These problems can be overcome by some drug delivery system like mouth dissolving tablets, dispersible tablets, effervescent tablets, etc. Aceclofenac is often used to relieve the inflammation, swelling, stiffness and joint pain which sometimes required fast onset of action. Aceclofenac effervescent tablet was prepared to enhance onset of action. Tablets were prepared using anhydrous citric acid, tartaric acid and effersoda as effervescent components by direct compression method. Solid dispersion of Aceclofenac with anhydrous lactose can be prepared to increase solubility of aceclofenac. The solid dispersions were evaluated for drug content, practical yield, solubility and DSC for drug complex study. Central composite design was used for optimization of aceclofenac effervescent tablet. The effervescent formulations were evaluated for physicochemical parameters, drug content, effervescent lag time, total effervescent time, in vitro drug release study, FTIR for compatibility and stability testing. Optimized formula showed more than 50% drug release after 5 min and hence faster onset of action. The study point of aceclofenac effervescent tablet is ease of administration, accuracy of dosing and faster onset of action.

Background: The histamine H2 receptor antagonist ranitidine is US FDA-approved for the treatment of gastroesophageal reflux disease and healing of erosive esophagitis in children ≥1 month of age. A low-dose strength of ranitidine is now available in a citrus-flavored 25mg effervescent tablet (dissolved in 5mL of water); this formulation was developed to facilitate use in infants and smaller children. Ranitidine syrup is available in a peppermint-flavored 15 mg/mL formulation. Objective: To compare taste preferences for ranitidine (Zantac®) syrup and ranitidine effervescent tablets dissolved in water (Zantac® EFFERdose®) in healthy children aged 4–8 years and their adult caregivers. Study Design and Methods: A randomized, single-blind, crossover, taste test trial was conducted in 102 children and 102 parents/legal guardians. All subjects received a single 45mg dose of each formulation. After tasting both preparations children were asked: “Now that you have tasted both medicines, which one of these medicines do you think tastes better?” Adults were asked four questions to assess whether they would administer the medication to the children. Results: Seventy-one percent (72/102) of the children preferred the taste of the ranitidine effervescent tablets compared with 29% (30/102) who preferred the syrup (p < 0.001). The majority of adults (71%) responded that they would prefer to administer the effervescent formulation based on taste. Adverse events consistent with product labeling were mild and were reported in four children and three adults: headache (n = 3), drowsiness (n = 1), abdominal pain/cramps (n = 2), and bloating/gas (n = 1). Conclusion: The taste of the ranitidine effervescent formulation dissolved in water is preferred over the ranitidine syrup. Better taste acceptance may facilitate ease of administration and compliance in pediatric patients.

A rapid reversed-phase high-performance liquid chromatographic procedure is developed and validated for the simultaneous quantitation of aspirin, salicylic acid, and caffeine extracted from an effervescent tablet. The method uses a Hypersil C18 column (5 micro m, 15 cm x 4.6 mm) for an isocratic elution in a water-methanol-acetic acid mobile phase at a wavelength of 275 nm. The tablets' buffering effects and acid neutralizing capacity require an extraction solvent of methanol-formic acid. The range of linearity for aspirin is 0.5-1.25 mg/mL, caffeine 0.065-0.195 mg/mL, and salicylic acid 0.4-6.0% of aspirin. The overall recovery is 100.2%, 100.7%, and 99.2% for aspirin, caffeine, and salicylic acid, respectively. Under the conditions of the method, aspirin, caffeine, and salicylic acid are adequately resolved with proper peak symmetry in less than 7 min.

The purpose of the present study was to develop a simple and accurate HPLC method to measure the amount of each agent in a multidrug pharmaceutical formulation. Three drugs, acetaminophen, acetylsalicylic acid and ascorbic acid, were analyzed simultaneously. A commercial pharmaceutical effervescent tablet was examined and the amount of each of these agents successfully determined. The present method appears to be more convenient than the current procedures described in American and British Pharmacopoeias in which each drug is assayed separately.

The surface acidities of pharmaceutical excipients are detected by color changes of acid-base indicators on the substrate's surface. To quantify the indicator's transition interval on the surface of hydrophilic excipients, as an organic solvent methanol is introduced for the preparation of indicator-excipient mixtures. The influence of the particle size on the determination of the surface acidity is investigated and particle size did not influence the determination within the particle size range investigated. Surface acidities of common excipients used in preparation of solid dosage forms are presented.

The aim of this study was to measure the efficacy of 150-mg ranitidine effervescent tablets compared with 20-mg famotidine wafers in the management of patients presenting to primary care physicians with episodic symptoms of gastro-oesophageal reflux disease (GORD).The study was of a multicentre, open, randomized, parallel-group design in which 32 Norwegian general practitioners participated. After a pre-treatment demographic and symptom assessment, eligible patients were allocated to either ranitidine effervescent tablet or famotidine wafer. Patients were then provided with the study medication, a stopwatch, and a 2-week symptom diary card. Efficacy was primarily determined by the time to adequate symptom relief for the first symptom episode.In total, 377 patients were recruited to the study; 187 patients received ranitidine effervescent, and 190 received famotidine wafer. More than 50% of the patients had daily GORD symptoms before recruitment. Median time to adequate symptom relief was 15 min in the ranitidine group and 18.5 min in the famotidine group (P = 0.005). Adequate symptom relief within 60 min was reported by 165 (92%) ranitidine patients and 156 (84%) famotidine patients (P = 0.02). The number of non-responders after 60 min was twice as great in the famotidine group: 30 (16%) versus 15 (8%). A greater proportion of patients in the famotidine group liked taking the wafer formulation: 173 (94%) versus 126 (70%) (P = 0.001).There was a statistically significant difference in favour of 150-mg ranitidine effervescent tablets in terms of time to adequate symptom relief and the proportion of patients who achieved adequate symptom relief for the first episode. A greater proportion of patients in the famotidine group liked the type of formulation than in the ranitidine group.

Intestinal absorption of calcium from three different labelled calcium preparations (all containing 500 mg elemental calcium) was determined using the whole body retention and urinary excretion of 47Ca in 14 normal subjects. Chewable calcium carbonate tablets showed a significantly (p less than 0.05) better mean minimum absorption of calcium (25.6% in exp. I, 22.8% in exp. II) than calcium given in the form of a lactogluconate/carbonate effervescent tablet, (17%), but similar to calcium in a chloride solution (24.7%). The minimum calcium absorption varied from 85 to 128 mg. All the preparations were taken with standardized low calcium test meals.

The aim of this work was to benefit from the advantageous technique of tablet manufacture by direct compression for the easy preparation of stable effervescent tablets. In order to overcome the bad flowability and low compressibility of sodium bicarbonate, a common carbon dioxide source in effervescent tablet formulation, a spray-drying technique was applied. The adjustment to achieve different conditions when operating the spray-dryer was described. Some additives such as polyvinylpyrrolidone and silicon oil were found to be essential to obtain direct compressible spray-dried sodium bicarbonate. The prepared spray-dried sodium bicarbonate showed good compression characteristics and excellent compressibility without being transformed into sodium carbonate.

SummaryA multi-centre, double-blind controlled study in eleven hospitals was carried out to assess the efficacy, tolerance and patients' acceptance of a new ‘Mycostatin’ effer-vescent vaginal tablet (E.V.T.). One hundred and ninety-one patients received the effervescent tablet and 96 patients the currently-available ‘Mycostatin’ pessary. Both formulations, containing 100,000 units of nystatin per pessary or tablet, were initially prescribed as one tablet or pessary nocte for 14 days. The patients selected had signs and symptoms of candidal vaginitis confirmed by either a positive wet smear or culture for Candida albicans.The new effervescent formulation disintegrated and dispersed completely, resulting in a more uniform distribution of the active material throughout the vaginal walls (p =0.002). After 14 days treatment 87% of the patients were clinically and mycologically clear of candidal vaginitis. A further 7 days therapy with one E.V.T. twice daily resulted in a complete cure in all but 5 patients (2....

Codeine phosphate in a paracetamol:codeine effervescent tablet was found to react at room temperature and 37 degrees C with the citric acid constituent to form citrate esters of codeine. The esterification was confirmed in a solid-state reaction at elevated temperature. The structures of the three possible monosubstituted esters (1-3) were elucidated from spectroscopic data (nuclear magnetic resonance and mass spectrometry) and by selective hydrolysis of the dimethyl esters to give symmetrical and asymmetrical dimethyl citrates. In the degradation reaction, formation of the symmetrically substituted citrate ester of codeine, 1, was found to predominate. Tartaric acid, which can be used in effervescent tablet formulations, was also found to give an ester with codeine phosphate in a similar nonsolvolytic reaction. A liquid chromatographic method was developed for the separation of the citrate esters of codeine.

A new dosage form of levodopa, which has the characteristics of loading high concentrations of levodopa at the upper part of the intestine, has been developed to improve its bioavailability. It is shown that an effervescent tablet formulation, coated with hydroxypropyl methylcellulose phthalate (carboxybenzoyl radical content: 20–24%) as the enteric material, is suitable for the purpose of dissolution. This was confirmed from animal experiments, which showed that tablets of this composition disintegrate instantly on reaching the upper part of the intestine. This tablet was considered appropriate for the bioavailability tests described in this paper.

A stability-indicating analytical method is described for determining acetaminophen and its degradation product, p-aminophenol, in an effervescent tablet. Tablets assayed by ion-pair high-performance reversed-phase liquid partition chromatography required no sample cleanup. The method applied to tablets containing 325 mg of acetaminophen yielded an average recovery of 99.6% with a relative standard deviation of 0.70% (n = 10). As little as 0.005% p-aminophenol could be detected.

To the Editor.— Despite previous widespread publicity concerning the hazards of enteric-coated potassium supplements, these preparations are still commercially available, prescribed, and dispensed. This was shown recently in a survey that we conducted of 25 pharmacies in the San Francisco metropolitan area. The notion that enteric-coated potassium salts are safer and less irritating to the gastrointestinal tract persists, and the hazards associated with their use are not generally recognized. Repeated reports have confirmed the association of intestinal as well as gastric ulceration with the administration of enteric-coated tablets of potassium chloride alone or in combination with thiazide diuretics. In addition to their hazards, the need for these preparations has been eliminated with the introduction of potassium-sparing diuretics and the availability of potassium supplementation in liquid and effervescent tablet forms. Initial report of small bowel ulceration associated with the administration of enteric-coated potassium supplements appeared in the mid 1960s. More recent reports

Fatal cinchophen poisonings due to various proprietary preparations have been reported quite extensively by Johnson, 1 Weir and Comfort, 2 Parsons and Harding, 3 and others in the recent literature. The case I am reporting is prompted by the peculiar circumstances involved in the patient's death, and by the fact that the preparation consumed is a rather recent addition to the proprietary cinchophen compounds. Cinsa-Vess, an effervescent tablet containing as its essential ingredients 5 grains (0.3 Gm.) of cinchophen and 1/200 grain (0.0003 Gm.) of colchicine, appeared for the first time on record in the files of the Council on Pharmacy and Chemistry in November 1930. 4 The patient consumed thirty tablets of this product over a period of three months prior to the first signs of jaundice, a quantity equivalent to 150 grains (10 Gm.) of cinchophen and one-sixth grain (0.01 Gm.) of colchicine.