Gas-forming Agent Research Articles

Design and evaluation of effervescent floating tablets based on hydroxyethyl cellulose and sodium alginate using pentoxifylline as a model drug.

The aim of this work was to design and evaluate effervescent floating gastro-retentive drug delivery matrix tablets with sustained-release behavior using a binary mixture of hydroxyethyl cellulose and sodium alginate. Pentoxifylline was used as a highly water-soluble, short half-life model drug with a high density. The floating capacity, swelling, and drug release behaviors of drug-loaded matrix tablets were evaluated in 0.1 N HCl (pH 1.2) at 37°C±0.5°C. Release data were analyzed by fitting the power law model of Korsmeyer–Peppas. The effect of different formulation variables was investigated, such as wet granulation, sodium bicarbonate gas-forming agent level, and tablet hardness properties. Statistical analysis was applied by paired sample t-test and one-way analysis of variance depending on the type of data to determine significant effect of different parameters. All prepared tablets through wet granulation showed acceptable physicochemical properties and their drug release profiles followed non-Fickian diffusion. They could float on the surface of dissolution medium and sustain drug release over 24 hours. Tablets prepared with 20% w/w sodium bicarbonate at 50–54 N hardness were promising with respect to their floating lag time, floating duration, swelling ability, and sustained drug release profile.

Development of ranolazine loaded floating biomaterial gellan beads using Box-Behnken factorial design

The present work aimed at development of ranolazine loaded floating biomaterial gellan beads to enhance its site specific absorption. The beads obtained by ionotropic gelation method using sodium bicarbonate as gas-forming agent, calcium chloride and chitosan as a crosslinker were evaluated for physicochemical properties and in vitro performance. Yield and entrapment efficiency varied from 90 to 97% and 58 to 81% respectively. Surface topography revealed spherical microparticles with evenly distributed pores. Differential scanning calorimetry and powder X-ray diffraction pointed out amorphous nature of the drug. Effect of formulation variables on floating lag time and time required for 50% drug release was studied using Box-Behnken factorial design. The beads displayed good in vitro floatability in 0·1 N HCl with initial burst release followed by a controlled release up to 10 h whereas slow drug release was observed in phosphate buffer pH 6·8; probably due to decreased drug solubility and accelerated internal gelation through ionic crosslinking of gellan monomers. The beads, when studied in non-everted rat stomach and intestinal sac models, demonstrated twofold decrease in flux and apparent permeability coefficient as compared to pure ranolazine. Floating gellan beads proved advantageous for controlling the release and enhancing therapeutic activity of ranolazine.

Formulation and evaluation of gastroretentive floating drug delivery system of dipyridamole

A multiple-unit floating alginate bead drug delivery system with prolonged stomach retention time was developed in this study. The floating alginate beads were prepared by ionic cross-linking method, using CaCO3 as the gas-forming agent. Over 92% of the beads remained floating after 9 h. In order to prepare sustained-release dosage forms of dipyridamole, the solid dispersion technique was applied using a blend of Eudragit L100 and Eudragit RLPO. Afterwards, the solid dispersions of dipyridamole were incorporated into the floating alginate beads. The drug release was modified by changing the ratio of Eudragit RLPO and Eudragit L100 in the solid dispersions. The in vivo results showed that the relative bioavailability of alginate beads was enhanced by approximately 2.52-fold compared with that of the commercial tablet. Therefore, our study illustrated the potential use of floating alginate beads combined with the solid dispersion technique for the delivery of acid-soluble compounds, such as dipyridamole.

Gastro-floating tablets of cephalexin: Preparation and in vitro/in vivo evaluation

Gastro-floating tablets of cephalexin were developed to prolong the residence time in major absorption sites. Gastro-floating tablets were prepared and optimized using hydroxypropyl methylcellulose (HPMC K100M) as matrix and sodium bicarbonate as a gas-forming agent. The properties of the tablets in terms of floating lag time, floating time and in vitro release were evaluated. Furthermore, in vivo pharmacokinetic study in fed and fasted beagle dogs was performed. The gastro-floating tablets had short floating lag time and exhibited a satisfactory sustained-release profile in vitro. Compared with conventional capsules, the gastro-floating tablets presented a sustained-release behavior with a relative bioavailability of 99.4%, while the reference sustained-release tablets gave a relative bioavailability of only 39.3%. Meanwhile, the food had significant effect on the pharmacokinetics of sustained-release tablets. It was concluded that the gastro-floating tablets had a sustained-release effect in vitro and in vivo, as well as desired pharmacokinetic properties in both fed and fasted conditions.

Development of a floating multiple unit controlled-release beads of zidovudine for the treatment of AIDS

Zidovudine is the first approved compound for the treatment of AIDS, and having short biological half-life and poor bioavailability. The present research work an attempt has been made to design the zidovudine gas powered multiple unit drug delivery system for controlled release. Floating beads are often used for controlled drug release as they have a gastroretentive property without affecting the gastric emptying rate. In the present study zidovudine-controlled release beads were prepared with the help of the ionotropic gelation method, using sodium alginate containing KHCO3 as the gas-forming agent. The beads were subjected to in-vitro drug release, kinetic studies and stability studies. FTIR and DSC studies shown there was no interaction between drug and polymers. The percentage of zidovudine content from the beads was determined by UV-spectroscopy and ranged from 93.76 ± 0.44 to 98.14 ± 1.10. The in-vitro percentage release of zidovudine from the beads at the end of 12 h ranged from 86.10424 to 96.83746. The kinetic studies revealed that the drug was released by zero-order kinetics. The optimized formulations were subjected to stability studies and shown there were no significant changes in drug content, physicochemical parameters and release pattern. The floating beads designed for the gastroretentive dosage form could be suitable for controlled drug delivery.

Development of Novel Gastroretentive Floating Particulate Drug Delivery System of Gliclazide

The objective of present project was to improve the dissolution profile of gliclazide by developing floating alginate beads using various biodegradable polymers like gelatin, pectin and hydroxypropylmethylcellulose (HPMC). The floating beads were prepared by a simple ionotropic gelatin method using calcium carbonate as gas generating agent. The developed beads were characterized by Fourier transform infrared spectroscopy analysis, differential scanning calorimetry, X-ray diffraction analysis and scanning electron microscopy (SEM). The prepared beads showed good in vitro floatation, which was dependent on the concentration of gas-forming agent. SEM photomicrographs confirmed that the developed beads were spherical in shape and had particle size in the range of 730 to 890 μm. The incorporation efficiency was found to be in the range of 59.96 to 85.1%. The cumulative percent drug release from the beads after 10 h dissolution study at pH 1.2 and pH 5.8 was in the range of 33 to 46% and 82 to 95% respectively. The concentration of the gas generating agent was found to influence the release rate. The mechanism of drug release was Fickian diffusion with swelling. The in vivo sub-acute hypoglycemic study in high fat diet induced diabetic C57BL/6J mice demonstrated significant (p < 0.05) hypoglycemic effect over a period of 12 h and 24 h, respectively, with HPMC and pectin beads. A significant (p & 0.05) reduction in fasting and non-fasting blood glucose levels, reduction in fasting plasma insulin level and a significant improvement in glucose tolerance were observed in animals treated with formulations. The developed beads were suitable carriers for improving the systemic absorption of gliclazide and maintaining reduced blood glucose levels.

Test on the Mortar Mix Ratio with Aeolian Sand of Mu Us Desert

In this paper, series of mortar tests with Aeolian sand as its fine aggregate were launched. Result shows that the admixture flyash can effectively improve the liquidity and water capacity, hence to improve the workability of the mortar. As the mortar age increases, with the surface activity of flyash gradually brought into full play, the long-term mortar strength can be ensured. The compound additive with polycarboxylic as the water reducing agent, neopelex as the gas-forming agent and the sodium silicate, reduced the required water by about 15% without changing the consistency of the mortar mixture. United Expansive Agent (UEA) was used to reduce the shrinkage rate of the mortar mixture. The Cost Performance Indicator (CPI) was introduced to evaluate the cost performance of the mix mortar, suggesting that the CPI of the mix mortar is 1.38 times of that of the mortar with river sand. Test results of various index value shows that the mortar mix ratio obtained in this paper can meet the need of plastering and masonry engineering.

Floating Drug Delivery of Nevirapine as a Gastroretentive System

A multiple-unit floating drug delivery system based on gas formation technique was developed, in order to prolong the gastric residence time and to increase the overall bioavailability of the dosage form. The floating bead formulations were prepared by dispersing nevirapine together with calcium carbonate in a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as the alginate underwent ionotropic gelation by calcium ions, and carbon dioxide developed from the reaction of carbonate salts with acid. The obtained beads were able to float due to CO2-gas formation and the gas entrapment by the polymeric membrane. The prepared beads were evaluated for percent drug loading, drug entrapment efficiency, morphology, surface topography, buoyancy, in-vitro release, and release kinetics. The formulations were optimized for different weight ratios of the gas-forming agent and sodium alginate. The beads containing higher amounts of calcium carbonate demonstrated an instantaneous, complete, and excellent floating ability over a period of 24 hours. The increased amount of the gas forming agent did not affect the time to float, but increased the drug release from the floating beads, while increasing the coating level of the gas-entrapped membrane, increased the time to float, and slightly retarded the drug release. Good floating properties and sustained drug release were achieved. Finally, these floating beads seemed to be a promising gastroretentive drug delivery system.

Evaluation of drug release kinetics and physico-chemical characteristics of metronidazole floating beads based on calcium silicate and gas-forming agents

In the present investigation metronidazole-loaded alginate beads consisting of calcium silicate as a porous carrier or NaHCO3 as a gas-forming agent were prepared for local eradication of Helicobacter Pylori. Gelation method was used for preparation of conventional sodium alginate beads. Drug entrapment efficiency, drug loading, floating properties, drug release, crystallinity and release kinetic as well as morphology of the prepared beads were assessed. The silicate based beads showed slower release pattern, compared to the gas-forming beads due to network structure strengthening effect of the calcium silicate. Furthermore, the gas-forming-based beads had shorter initial buoyancy lag time, owing to the fact that the NaHCO3 produced larger pores than those of silicate treated ones. Drug entrapment efficiency ranged between 61.7 and 93.1% for the prepared formulations. The maximum value of drug loading for gas-forming and silicate-based beads were 66.64% and 34.97%, respectively. Kinetically, release pattern of metronidazole in simulated gastric fluid from the beads fitted best to Reciprocal powered time, Weibull and log-probability models with the respect overall mean percentage error values of 4.50, 5.30 and 7.76. By and large, these systems can float in the gastric condition and control the drug release from the beads.

Preparation and evaluation of novel metronidazole sustained release and floating matrix tablets

In the present study, metronidazole was used for preparing floating dosage forms that are designed to retain in the stomach for a long time and have developed as a drug delivery system for better eradication of Helicobacter Pylori in peptic ulcer diseases. For this means, various formulations were designed using multi-factorial design. HPMC, psyllium and carbopol in different concentrations were used as floating agents, and sodium bicarbonate was added as a gas-forming agent. Hardness, friability, drug loading, floating ability and release profiles as well as kinetics of release were assessed. Formulations containing HPMC as filler showed prolonged lag times for buoyancy. Adding psyllium to these formulations had reduced relative lag times. Overall, selected formulations were able to float immediately and showed buoyancy for at least 8 h. Meanwhile, sustained profiles of drug release were also obtained. Kinetically, among the 10 assessed models, the release pattern of metronidazole from the tablets fitted best to Power law, Weibull and Higuchi models in respect overall to mean percentage error values of 3.8, 4.73 and 5.77, respectively, for calcium carbonate-based tablets and, 2.95, 6.39 and 3.9, respectively, for calcium silicate-based tablets. In general, these systems can float in the gastric condition and control the drug release from the tablets.

In Vitro Release Kinetics and Bioavailability of Gastroretentive Cinnarizine Hydrochloride Tablet

An oral sustained release dosage form of cinnarizine HCl (CNZ) based on gastric floating matrix tablets was studied. The release of CNZ from different floating matrix formulations containing four viscosity grades of hydroxypropyl methylcellulose, sodium alginate or polyethylene oxide, and gas-forming agent (sodium bicarbonate or calcium carbonate) was studied in simulated gastric fluid (pH 1.2). CNZ release data from the matrix tablets were analyzed kinetically using Higuchi, Peppas, Weibull, and Vergnaud models. From water uptake, matrix erosion studies, and drug release data, the overall release mechanism can be explained as a result of rapid hydration of polymer on the surface of the floating tablet and formation of a gel layer surrounding the matrix that controls water penetration into its center. On the basis of in vitro release data, batch HP1 (CNZ, HPMC-K100LV, SBC, LTS, and MgS) was subjected to bioavailability studies in rabbits and was compared with CNZ suspension. It was concluded that the greater bioavailability of HP1 was due to its longer retention in the gastric environment of the test animal. Batch no. HP1 of floating tablet in rabbits demonstrated that the floating tablet CNZ could be a 24-h sustained release formulation.

Evaluation of drug release kinetics and physico-chemical characteristics of metronidazole floating beads based on calcium silicate and gas-forming agents

Evaluation of drug release kinetics and physico-chemical characteristics of metronidazole floating beads based on calcium silicate and gas-forming agents

Development and evaluation of new sustained-release floating microspheres

A type of multi-unit floating alginate (Alg) microspheres was prepared by the ionotropic gelation method with calcium carbonate (CaCO 3) being used as gas-forming agent. Attempts were made to enhance the drug encapsulation efficiency and delay the drug release by adding chitosan (Cs) into the gelation medium and by coating with Eudragit, respectively. The gastrointestinal transit of optimized floating sustained-release microspheres was compared with that of the non-floating system manufactured from identical material using the technique of gamma-scintigraphy in healthy human volunteers. It was found that the drug encapsulation efficiency of Cs–Alg microspheres was much higher than that of the Ca–Alg microspheres, and coating the microspheres with Eudragit RS could extend the drug release significantly. Both uncoating and coating microspheres were able to continuously float over the simulated gastric fluid (SGF) for 24 h in vitro. Prolonged gastricretention time (GRT) of over 5 h was achieved in the volunteer for the optimized coating floating microspheres (FM). In contrast, non-floating system (NFM) could be emptied within 2.5 h. In the present study, a multi-unit system with excellent floating ability, optimum drug entrapment efficiency and suitable drug release pattern has been developed.

Stomach-specific drug delivery of 5-fluorouracil using floating alginate beads

A multiple-unit-type oral floating dosage form (FDF) of 5-fluorouracil (5-FU) was developed to prolong gastric residence time, target stomach cancer, and increase drug bioavailability. The floating bead formulations were prepared by dispersing 5-FU together with calcium carbonate into a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as alginate undergoes ionotropic gelation by calcium ions and carbon dioxide develops from the reaction of carbonate salts with acid. The evolving gas permeated through the alginate matrix, leaving gas bubbles or pores, which provided the beads buoyancy. The prepared beads were evaluated for percent drug loading, drug entrapment efficiency, image, surface topography, buoyancy, and in vitro release. The formulations were optimized for different weight ratios of gas-forming agent and sodium alginate. The beads containing higher amounts of calcium carbonate demonstrated instantaneous, complete, and excellent floating ability over a period of 24 hours. The optimized formulation was subjected to in vivo antitumor studies to check the therapeutic efficacy of the floating dosage forms containing 5-FU against benzo(a)pyrene-induced stomach tumors in albino female mice (Balb/C strain). The multiple-bead FDF was found to reduce the tumor incidence in mice by 74%, while the conventional tablet dosage form reduced this incidence by only 25%. Results indicate that FDF performed significantly better than the simple tablet dosage form.

Development and evaluation of a novel floating in situ gelling system of amoxicillin for eradication of Helicobacter pylori

The aim of this study was to develop a new intra-gastric floating in situ gelling system for controlled delivery of amoxicillin for the treatment of peptic ulcer disease caused by Helicobacter pylori (H. pylori). Gellan based amoxicillin floating in situ gelling systems (AFIG) were prepared by dissolving varying concentrations of gellan gum in deionized water containing sodium citrate, to which varying concentrations of drug and calcium carbonate, as gas-forming agent, was added and dissolved by stirring. The formulation variables like concentration of gellan gum and calcium carbonate significantly affected the in vitro drug release from the prepared AFIG. The in vivo H. pylori clearance efficacy of prepared AFIG in reference to amoxicillin suspension following repeated oral administration to H. pylori infected Mongolian gerbils was examined by polymerase chain reaction (PCR) technique and by a microbial culture method. AFIG showed a significant anti-H. pylori effect in the in vivo gerbil model. It was noted that the required amount of amoxicillin for eradication of H. pylori was 10 times less in AFIG than from the corresponding amoxicillin suspension. The results further substantiated that the prepared AFIG has feasibility of forming rigid gels in the gastric environment and eradicated H. pylori from the gastrointestinal tract more effectively than amoxicillin suspension because of the prolonged gastrointestinal residence time of the formulation.

Use of pectin as a carrier for intragastric floating drug delivery: Carbonate salt contained beads

Pectin has been investigated as a carrier for an intragastric floating drug delivery by a means of calcium pectinate gel (CaPG) beads. The CaPG beads containing carbonate salt, as a gas-forming agent, were prepared by dispersing carbonate salt in pectin solution and then extruding into either neutral or acidified solution of calcium chloride. The effect of selected factors, such as type of carbonates, percentage of carbonates, degree of methylesterification (DE) of pectin, type of gelation medium, drug loading and drying method, on morphology, floating and release properties was investigated. Incorporation of sodium bicarbonate into pectin solution resulted in porous structured beads. Acidity of gelation medium increased the pores in the structure of beads containing calcium carbonate. This is due to carbon dioxide generated from reaction of carbonate salts with acid. Drug release from CaPG beads is clearly dependent upon the formulation and processing variables studied. It is obvious that the highly porous of the freeze-dried beads showed a good floating ability with fast drug release. The drug release could be prolonged by using pectin with lower DE, 10% calcium carbonate, acidified gelation medium, and high drug loading. However, their floating ability seemed to be decreased. It is suggested that the optimization of formulation and processing variables is further needed to obtain a good floating ability and a prolonged drug release.

Use of Natural Coralline Biomaterials As Reinforcing and Gas-Forming Agent for Developing Novel Hybrid Biomatrices: Microarchitectural and Mechanical Studies

Use of Natural Coralline Biomaterials As Reinforcing and Gas-Forming Agent for Developing Novel Hybrid Biomatrices: Microarchitectural and Mechanical Studies

Use of Natural Coralline Biomaterials As Reinforcing and Gas-Forming Agent for Developing Novel Hybrid Biomatrices: Microarchitectural and Mechanical Studies

This paper describes the first attempt in fabrication of three-dimensional macroporous composites of chitosan and natural coralline material with pore sizes of 300-400 microm, exceeding the upper pore size limit of 250 microm obtained with freeze-dried chitosan-based scaffolds. Natural coral particulates of less than 20 microm, which is mainly composed of calcium carbonate (CaCO3), was simultaneously used as reinforcing phase and gas-forming agent to obtain a structure with large pores and improved mechanical and biological properties. The reaction between the coralline material and the acidic chitosan polymer solvent, which produced carbon dioxide, was rapidly stopped by the subsequent thermally induced phase separation technique, leaving coralline particulates in the polymeric structure. Scaffolds containing five different proportions of coralline material (0, 25, 50, 75, and 100 wt%) were investigated. The coralline-chitosan weight ratio was studied for its effects on the physical properties of the scaffolds. The relation between scaffold microarchitecture and mechanical properties was assessed with scanning electron microscope (SEM), along with micro-CT imaging and compression testing. The scaffolds were used in bone marrow cell culturing experiments to assess the effect of composition on cell behavior through cell-material interaction and morphological observation by SEM. Higher coralline concentration increased the pore wall thickness and favored large pore formation. Varying the coralline particulate to chitosan polymer ratio from 0 to 75 wt% increased the average pore size from 80 microm to 400 microm while the porosity decreased from 91% to 78%. The compressive modulus was improved proportionally with the coralline content, and the 75 wt% composites had a significantly higher modulus than other chitosan-based scaffold groups. More cells were observed on scaffolds with higher coralline content. The cell culture experiments indicated that the scaffolds containing coralline material might have a high cell affinity, since it allowed fast cell attachment and spreading.

A Novel Drug Delivery System Design for Meloxicam

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.

The radiological management of oesophageal food bolus obstruction using a gas-forming agent and barium

Removal of an impacted food bolus in the lower oesophagus at rigid oesophagoscopy is challenging and carries a significant risk of perforation. We present two cases which were successfully disimpacted radiologically, in order to raise awareness among otolaryngologists of this therapeutic option.