Development and Optimization of Microballoons Assisted Floating Tablets of Baclofen.

The objective of the present study was to develop microballoons aided gastro-retentive floating tablets of baclofen, a skeletal muscle relaxant with a low elimination half-life of ~ 3.5 h. Baclofen floating tablet was prepared to offer convenience by designing a tablet that would float in the stomach for a prolonged period and allow controlled drug release to enable once-a-day administration. Ethylcellulose microballoons (ECMBs) prepared by pseudo emulsion solvent diffusion method were employed as floating aid. The ECMBs were spherical with a size of 446.71 µm and a circularity index of 0.995. Buoyancy of 98.90 percent and good flowability reflected by an angle of repose of 23° suggested the feasibility of preparing floating tablets by direct compression. Directly compressed baclofen floating tablets comprised ECMBs, HPMC-K15M, and hydroxyl ethylcellulose as independent variables in the Box-Behnken design, however, performance characteristics of tablets such as in vitro drug release, floating lag time, and swelling index were selected as the dependent variables. Among the variables, ECMBs played a critical role in ensuring buoyancy. However, HPMC-K15M significantly influenced in vitro drug release. The optimized batch displayed Hickson-Crowell kinetics and exhibited a similar drug release profile as a marketed once-a-day formulation (f2, 91.03). Furthermore, optimized tablets showed a swelling index of > 300, floating lag time < 3 s, and total floating time > 24 h. Microballoons assisted floating tablets exhibited great promise for assured gastric retention of tablets.

Physical, Thermal, and Chemical Properties of Fly Ash Cenospheres Obtained from Different Sources.

Cenospheres are hollow particles in fly ash, a by-product of coal burning, and are widely used as a reinforcement when developing low-density composites called syntactic foams. This study has investigated the physical, chemical, and thermal properties of cenospheres obtained from three different sources, designated as CS1, CS2, and CS3, for the development of syntactic foams. Cenospheres with particle sizes ranging from 40 to 500 µm were studied. Different particle distribution by size was observed, and the most uniform distribution of CS particles was in the case of CS2: above 74% with dimensions from 100 to 150 µm. The CS bulk had a similar density for all samples and amounted to around 0.4 g·cm-3, with a particle shell material density of 2.1 g·cm-3. Post-heat-treatment samples showed the development of a SiO2 phase in the cenospheres, which was not present in the as-received product. CS3 had the highest quantity of Si compared to the other two, showing the difference in source quality. Energy-dispersive X-ray spectrometry and a chemical analysis of the CS revealed that the main components of the studied CS were SiO2 and Al2O3. In the case of CS1 and CS2, the sum of these components was on average from 93 to 95%. In the case of CS3, the sum of SiO2 and Al2O3 did not exceed 86%, and Fe2O3 and K2O were present in appreciable quantities in CS3. Cenospheres CS1 and CS2 did not sinter during heat treatment up to 1200 °C, while sample CS3 was already subjected to sintering at 1100 °C because of the presence of a quartz phase, Fe2O3 and K2O. For the application of a metallic layer and subsequent consolidation via spark plasma sintering, CS2 can be deemed the most physically, thermally, and chemically suitable.

Pneumatic Microballoons for Active Control of the Vibration-Induced Flow.

Vibration-induced flow (VIF), in which a mean flow is induced around a microstructure by applying periodic vibrations, is increasingly used as an active flow-control technique at the microscale. In this study, we have developed a microdevice that actively controls the VIF patterns using elastic membrane protrusions (microballoons) actuated by pneumatic pressure. This device enables on-demand spatial and temporal fluid manipulation using a single device that cannot be achieved using a conventional fixed-structure arrangement. We successfully demonstrated that the device achieved displacements of up to 38 µm using the device within a pressure range of 0 to 30 kPa, indicating the suitability of the device for microfluidic applications. Using this active microballoon array, we demonstrated that the device can actively manipulate the flow field and induce swirling flows. Furthermore, we achieved selective actuation of the microballoon using this system. By applying air pressure from a multi-input channel system through a connection tube, the microballoons corresponding to each air channel can be selectively actuated. This enabled precise control of the flow field and periodic switching of the flow patterns using a single chip. In summary, the proposed microdevice provides active control of VIF patterns and has potential applications in advanced microfluidics, such as fluid mixing and particle manipulation.

On the Role of Hollow Aluminium Oxide Microballoons during Machining of AZ31 Magnesium Syntactic Foam.

The role played by hollow ceramic thin-walled aluminium oxide microballoons on the shear deformation characteristics of AZ31 Magnesium syntactic foam is studied through high-speed machining. The ceramic microballoons embedded in the AZ31 matrix provides the necessary stiffness for these novel foams. The effect of hollow ceramic microballoon properties, such as the volume fraction, thin wall thickness to diameter ratio, and microballoon diameter, profoundly affects the chip formation. A novel force model has been proposed to explain the causes of variation in cutting forces during chip formation. The results showed an increase in machining forces during cutting AZ31 foams dispersed with higher volume fraction and finer microballoons. At a lower (Davg/h) ratio, the mode of microballoon deformation was a combination of bubble burst and fracture through an effective load transfer mechanism with the plastic AZ31 Mg matrix. The developed force model explained the key role played by AZ31 matrix/alumina microballoon on tool surface friction and showed a better agreement with measured machining forces.

Design and optimization of gastro-retentive microballoons for enhanced bioavailability of cinnarizine.

This study is focused on the design of gastro-retentive drug delivery system composed of hollow microspheres (microballoons) for the sustained delivery of cinnarizine (CIN). The microballoons (MBs) were prepared by the emulsion solvent diffusion method using cellulose acetate butyrate (CAB) as the hosting polymer and absolute ethanol (ETH) and dichloromethane (DCM) as solvents. A 3(3) full factorial experimental design was adopted to study the effect of different variables and to find an optimum formula with desired properties. Prepared microballoons showed high drug loading capacities and controlled release behaviour. The optimum formulation was chosen on the basis of achieving maximum values for both drug loading capacity and release efficiency as well as having suitable size. The optimized MB (MB-F21) was composed of 200 mg CIN and 400 mg CAB with a DCM/ETH ratio of 2:1. Scanning electron microscopy for the optimum formulation showed a spherical outline with internal porous structure. An in vivo study using human volunteers was performed by determination of CIN concentration in the plasma using the liquid chromatography-mass spectrometry (LC-MS) method. Results proved the superiority of the designed formulation over the market product Stuval® tablets in bioavailability parameters comprising T max as well as area under the plasma CIN concentration-time curve (AUC0-24 h) and AUC0-∞ values. Also, the significantly greater value of mean residence time (MRT) in case of MB-F21 indicates its higher gastric residence time and proves the advantages of micro-multiparticulate dosage forms over conventional one.

Hollow Superparamagnetic Microballoons from Lifelike, Self-Directed Pickering Emulsions Based on Patchy Nanoparticles.

Herein, the formation of hollow microballoons derived from superparamagnetic iron oxide nanoparticles with silica patches is reported. Depending on the experimental conditions, single- or multishelled superparamagnetic microballoons as well as multivesicular structures were obtained. We show how such structural changes follow a lifelike process that is based on self-directing Pickering emulsions. We further demonstrate that the key toward the formation of such complex architectures is the patchy nature of the nanoparticles. Interestingly, no well-defined ordering of patches on the particles surface is required, unlike what theorists formerly predicted. The resultant hollow microballoons may be turned into hollow carbonaceous magnetic microspheres by simple pyrolysis. This opens the way to additional potential applications for such ultralightweight (density: 0.16 g·cm-3) materials.

Stomach specific polymeric low density microballoons as a vector for extended delivery of rabeprazole and amoxicillin for treatment of peptic ulcer.

The study was intended to develop a new intra-gastric floating in situ microballoons system for controlled delivery of rabeprazole sodium and amoxicillin trihydrate for the treatment of peptic ulcer disease. Eudragit S-100 and hydroxypropyl methyl cellulose based low density microballoons systems were fabricated by employing varying concentrations of Eudragit S-100 and hydroxypropyl methyl cellulose, to which varying concentrations of drug was added, and formulated by stirring at various speed and time to optimize the process and formulation variable. The formulation variables like concentration and ratio of polymers significantly affected the in vitro drug release from the prepared floating device. The validation of the gastro-retentive potential of the prepared microballoons was carried out in rabbits by orally administration of microballoons formulation containing radio opaque material. The developed formulations showed improved buoyancy and lower ulcer index as compared to that seen with plain drugs. Ulcer protective efficacies were confirmed in ulcer-bearing mouse model. In conclusion, greater compatibility, higher gastro-retention and higher anti-ulcer activity of the presently fabricated formulations to improve potential of formulation for redefining ulcer treatment are presented here. These learning exposed a targeted and sustained drug delivery potential of prepared microballoons in gastric region for ulcer therapeutic intervention as corroborated by in vitro and in vivo findings and, thus, deserves further attention for improved ulcer treatment.

Formulation and characterization of floating microballoons of nizatidine for effective treatment of gastric ulcers in murine model.

BACKGROUND: The purpose of the present study was to formulate and characterize Nizatidine-encapsulated microballoons for enhancing bioavailability and increasing the residence time of drug in the gastrointestinal tract. METHODS: Microballoons were prepared using emulsion solvent diffusion method using Eudragit S-100 and HPMC as the polymer. The formulation process was optimized for polymer ratio, drug: polymer ratio, emulsifier concentration, stirring speed, stirring time. Optimized formulation was subjected to scanning electron microscopy, drug entrapment, buoyancy studies, in-vitro drug release and in-vivo floating efficiency (X-ray) study. In-vivo antiulcer activity was assessed by ethanol-induced ulcer in murine model. RESULTS: The microballoons were smooth and spherical in shape and were porous in nature due to hollow core. A sustained release of drug was observed for 12 h. Examination of the sequential X-ray images taken during the study clearly indicated that the optimized formulation remained buoyant and uniformly distributed in the gastric contents for a period of 12 h. In ethanol-induced ulcer model, drug-loaded Microballoon-treated group showed significant (p < 0.01) ulcer protection index as compared to free drug-treated group. CONCLUSION: Nizatidine-loaded floating microballoons may serve as a useful drug delivery system for prolonging the gastric residence time and effective treatment of gastric ulcers.

Formulation and Evaluation of Controlled Release Floating Microballoons of Stavudine.

The aim of this study was to formulate and evaluate stavudine floating microballoons for controlled drug release. Initially, the drug-loaded low-density granular pellets were prepared with hydroxypropyl methylcellulose E5 grade and by using isopropyl alcohol as a granulating fluid. Further, the low-density granular pellets were subjected to microencapsulation by an emulsion evaporation technique using ethyl cellulose 7 cps and Eudragit S 100 as coating polymers and 1% w/v polyethylene glycol 400 as aqueous phase. The prepared microballoons were characterized for their particle size analysis, angle of repose, and compressibility index. The in vitro release studies were performed in 0.1 N HCl as medium. The prepared microballoons were free-flowing and spherical in shape. From all the formulations, F5E and F5F can be considered as promising controlled release floating microballoons of stavudine providing first-order release over a period of 12 hours, with a minimum floating lag time of 1 minute. It was found that the ratio of the drug & polymer, stirring speed, and concentration of surfactant were the most significant variables which influenced the size of the stavudine microballoons under the applied experimental conditions.

Gastroretentive microballoons of metformin: Formulation development and characterization.

The present study involves preparation and evaluation of floating microballoons with metformin as model drug for prolongation of gastric residence time. The microballoons were prepared by the solvent evaporation method using polymers hydroxypropylmethyl cellulose and ethyl cellulose. The shape and surface morphology of prepared microballoons were characterized by optical and scanning electron microscopy, respectively. In vitro drug release studies were performed and drug release kinetics was evaluated using the linear regression method. Effects of stirring rate during preparation, polymer concentration, solvent composition and dissolution medium on the size of microballoons, and drug release were also observed. The prepared microballoons exhibited prolonged drug release (8 hours) and remained buoyant for >10 hours. The mean particle size increased and the drug release rate decreased at higher polymer concentration. No significant effect of the stirring rate during preparation on drug release was observed. In vitro studies demonstrated diffusion-controlled drug release from the microballoons.

In-vitro characterization of gastroretentive microballoons prepared by the emulsion solvent diffusion method.

Microballoons floatable on JPXIII No.1 solution were developed as a dosage form capable of floating in the stomach. Microballoons were prepared by the emulsion solvent diffusion method using enteric acrylic and other polymers with drug in a mixture of dichloromethane and ethanol. It was found that preparation temperature determined the formation of cavity inside the microsphere and the surface smoothness, determining the floatability and the drug release rate of the microballoons. The correlation between the buoyancy of microballoons and their physical properties, e.g. apparent density and roundness of microballoons were elucidated. The drug loading efficiency of microballoons was also determined. The optimum loading amount of metformin in the microballoons was found to impart ideal floatable properties to the microballoons. By fitting the data into zero order, first order and Highuchi model it was concluded that the release followed zero order release.