Mixture Of Mannitol Research Articles

Melting and Solidification Characteristic of Mixture of Two Types of Latent Heat Storage Material in Direct Contact Heat Exchanger

ABSTRACT The aim of this study is to develop a latent heat storage system designed to utilize waste heat from industrial processes in the mid-temperature range of 100–200°C. Mannitol and a mixture of mannitol and erythritol, both classified as sugar alcohols, were utilized as phase change materials in this study. The present study investigated the melting and solidification characteristics of the mixture of C M = 70mass% (with a composition of 70% mannitol and 30% erythritol by mass) for latent heat storage at approximately 150°C. Additionally, the study aims to experimentally establish the thermal performance of the mixture of C M = 70mass% in a direct contact heat exchanger during melting and solidification. Comparative analysis with mannitol was conducted to determine the melting and solidification behavior of the mixture of C M = 70mass%. Moreover, the heat transfer characteristics, including heat storage and heat release speed, were investigated. Finally, the heat transfer mechanism of each phase change material (PCM) was considered through the overall heat transfer rate. keyword : Phase change material(PCM), Direct contact heat exchanger, Mixture of C M =70mass%, melting & soidification behaviors, Overall coefficient of heat transfer.

Correlation of lactulose-to-mannitol ratios in plasma and urine for intestinal permeability assessment in pigs.

The lactulose-to-mannitol ratio test is a test to assess the disorders associated with gut permeability. The test requires an oral administration of the mixture of lactulose and mannitol and urine collection. The urinary ratio of lactulose to mannitol is an indicator of intestinal permeability. Due to the complexity of urine collection in animal studies, plasma exposure ratios of lactulose to mannitol compared to their urinary concentration ratios were evaluated following an oral administration of the sugar mixture in pigs. 10 pigs were orally dosed with a solution of lactulose and mannitol mixture. Plasma samples were collected at predose, 10 and 30 minutes and 2, 4, and 6 hours postdosing, and cumulated urinary samples were collected at 6 hours for liquid chromatography-mass spectrometry analysis. The ratios of pharmacokinetic parameters of lactulose to mannitol and the plasma sugar ratios at a single time point or the mean values of several time points were compared to their urinary sugar ratios. The results revealed that the lactulose-to-mannitol ratios of AUC0-6h, AUCextrap, and Cmax were correlated to the urinary sugar ratios, and the plasma sugar ratios of a single time point at 2, 4, or 6 hours and the mean values of those time points were also appropriate to replace their urinary ratios in pigs. Following an oral administration of lactulose and mannitol mixture, blood collection, and assay can be an option for assessing intestinal permeability, especially in animal studies.

Callus induction, suspension culture and protoplast isolation in Camellia oleifera

Camellia oleifera is a woody edible oil crop with economical importance. This study established an efficient protocol for the induction of callus, the multiplication of a suspension cell line, and the isolation and purification of protoplasts in Camellia oleifera. It is shown that the callus induction was best when anthers were treated with the hormone of 0.5 mg/L NAA (Naphthaleneacetic acid), 2.0 mg/L 2,4-D (2,4-Dichlorophenoxyacetic acid) and 0.5 mg/L 6-BA (6-Benzylaminopurine) at 4 °C for 15 days. Callus was further multiplied on MS (Murashige and Skoog) medium augmented with 5% coconut water, 2 mg/L 2,4-D, 0.5 mg/L 6-BA, pH 5.8. Though three types of induced callus transferred to the same liquid medium with the ratio of 1 g callus inoculated into 30 ml liquid medium, it was found that the suspension culture effect of loose particles callus was the best. The maximum yield (11.7 × 106/g·FW) and highest viability (95.1%) of protoplast were reached when cell suspension (cultured for 6 days) was inoculated for 14 h in enzyme solution made of 0.4 mol/L mannitol mixture solution, 1.0% (w/v) Cellulase R-10 and 1.0% (w/v) Macerozyme R-10. The study lays a foundation for future research in cell fusion and transient gene expression in Camellia oleifera.

Hydrophilic Sugars for Enhancing Dissolution Rate of Cilostazol: Effect of Wet Co-Processing

Background: Cilostazol is an anti-platelets drug with considerable antithrombotic effects in vivo. Therefore, it is widely used by elderly patients. However, it suffers from poor bioavailability due to its low aqueous solubility. The objective of this work was to enhance the dissolution of cilostazol with the aim of formulating fast dissolving tablets for geriatrics and those of swallowing difficulties. Methods: Ethanol-assisted co-grinding of cilostazol with sugar-based excipients was adopted. Sucralose and mannitol were used for this purpose as hydrophilic excipient as well as taste improving agents. The obtained products were investigated regarding differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction, scanning electron microscope (SEM) and in vitro drug dissolution. Fast disintegrating tablets were prepared and evaluated. Results: Thermal behavior of the developed products reflected reduced crystallinity, it also suggested possible existence of new crystalline species with sucralose. Eutexia was also suggested for mannitol mixtures, that was supported by X-ray diffraction data. SEM indicated size reduction with the deposition of the drug as submicron particles over the excipient surface. Co-processing markedly improved cilostazol dissolution compared to unprocessed drug. The optimized formulations were successively formulated into fast disintegrating tablets. Conclusion: This investigation introduced the wet grinding strategy with sugar excipients as a platform for the formulation of easy to use tablets with optimum drug release.

Preparation, Physicochemical Characterisation and DoE Optimisation of a Spray-Dried Dry Emulsion Platform for Delivery of a Poorly Soluble Drug, Simvastatin.

In the presented study, insight into the development and optimisation of the dry emulsion formulation and spray drying process is provided. The aim was to facilitate the dissolution of the poorly soluble, highly lipophilic drug, simvastatin, by forming spray-dried dry emulsion particles having adequate powder flow properties, while assuring sufficient drug content. Simvastatin and a mixture of caprylic, capric triglyceride and 1-oleoyl-rac-glycerol were employed as a model drug and solubilising oils, respectively. A matrix of the dry emulsions was composed at a fixed ratio mixture of mannitol and HPMC. Tween 20 was used in low amounts as the primary emulsion stabiliser. To facilitate process optimisation, a DoE surface response design was used to study the influence of formulation and process parameters on the particle size distribution, powder bulk properties, emulsion reconstitution ability, drug stability and process yield of spray-dried products. Two-fluid nozzle geometry was identified, studied and confirmed to be important for most product critical quality attributes. Models obtained after the study showed acceptable coefficients of determination and provided good insight in the relationship governing the process and product characteristics. Five model optimised products showed adequate process yield, suitable particle size distribution, good reconstitution ability and improved dissolution profile, when compared to a non-lipid-based tablet and the pure drug. However, the obtained dry emulsion powders exhibited poor flow character according to the Carr index. The optimised product was further analysed with NMR during lipolysis to gain insight into the species formed during digestion and the kinetics of their formation.

Co-spraying of carriers (mannitol-lactose) as a method to improve aerosolization performance of salbutamol sulfate dry powder inhaler

Although in dry powder inhaler (DPI) formulations a single carrier is used, a single carrier is not able to provide an excellent aerosolization performance when it is used in DPI formulations. Thereby, the aim of this study was to engineer a suitable ternary mixture of mannitol-lactose-leucine to be used in a DPI formulation with enhanced aerosolization performance. To this end, binary mixtures of mannitol:lactose containing a constant amount of leucine (5% w/w of carriers) were spray-dried as a single solution. Spray-dried samples were blended with salbutamol sulfate to determine the efficiency of their aerosolization performance. Interestingly, note that lactose was in its amorphous state stabilized by the presence of mannitol in the samples. Spray-dried mannitol without lactose showed a combination of the α- and β-polymorphic forms which was the case in all other ratios of mannitol:lactose. It was shown that the highest fine particle fraction (FPF) was 62.42 ± 4.21% which was obtained for the distinct binary mixtures (1:3 mannitol:lactose) compared to a single carrier. This study opens a new window to investigate further the implementation of binary mixtures of sugar carriers containing leucine in DPI formulations to overcome poor aerosolization performance the mentioned DPI formulations.

Optimization of microencapsulation conditions of transglutaminase by freeze drying.

Transglutaminase (TG), which is an important enzyme for food processing, can enhance the firmness, viscosity and water binding capacity of food products by catalyzing the cross-linking reaction of proteins. Since preservation of the enzyme activity is essential, the production of microencapsulated powder form of TG can be a great challenge to maintain its initial activity. In this study, TG was microencapsulated using a freeze drying technique and the effects of homogenization conditions and coating material ratios on the enzyme activity were investigated using D-optimal combined design. Mannitol, gum arabic and casein were chosen as coating materials and different homogenization times (1-5min) and homogenization rates (11,200-20,000rpm) were applied. The optimum conditions which ensure the maximum enzyme activity have been determined as 11,200 rpm of homogenization rate, 1.27min of homogenization time, and in addition a mixture of mannitol, gum arabic and casein with ratios 38.2, 40.2, and 21.6%, respectively. Most of the activity loss occurred in the homogenization stage and the coating materials preserved enzyme activity during freeze drying. At the optimum point, the remaining activity of the microencapsulated TG was 93% while that of the crude (without coating materials) TG was 64% at the same drying conditions. Moreover, the effects of the microencapsulation conditions on the physical properties of powder such as moisture content, color, particle, bulk and tapped densities, porosity and flowability were determined.

The Production of Reactive Oxygen Species in Human Erythrocytes during Cryopreservation with Glycerol and Polyethylene Glycol

Abstract—The production of reactive oxygen species in human erythrocytes during incubation in the presence of a glycerol–mannitol mixture and polyethylene glycol with a molecular weight of 1500 Da, as well as during hypothermic storage of cells cryopreserved under their protection, was studied. Analysis of the production of reactive oxygen species was carried out by flow cytometry using fluorescence indices of dichlorofluorescein. It was found that incubation in the glycerol–mannitol mixture, as well as cryopreservation and subsequent hypothermic storage, did not cause activation of the production of reactive oxygen species in erythrocytes. Polyethylene glycol caused the intensification of the production of reactive oxygen species both during incubation and storage of cryopreserved erythrocytes under hypothermia. Peculiarities of changes in the intensity of the production of reactive oxygen species in erythrocytes under the influence of cryoprotective agents and cryopreservation may have a significant impact on the stability of cells under stress and their ability to maintain functional integrity after returning to physiological conditions.

Fabrication of a Magnet-Assembled Alignment Device for the Amperometric Detection of Carbohydrates in Combination with CE

The article describes the preparation of a magnet-assembled alignment device for the amperometric detection of carbohydrates in combination with capillary electrophoresis (CE). It consists of a self-positioning copper disc detection electrode plate, an NdFeB magnet, a painted iron screw nut as well as a cap bearing a grounding electrode, an auxiliary electrode and a reference electrode. Coaxially aligned copper wire and stainless steel tube were enclosed between two poly(methyl methacrylate) plates by far infrared-assisted encapsulation to fabricate the self-positioning electrode plate. The performance and advantages of the alignment device were demonstrated by the separation and detection of standard mixtures of mannitol, sucrose, glucose and fructose by CE. The four carbohydrates were well separated within 13 min in a 40-cm long capillary at a separation voltage of 9 kV using a 75 mM NaOH aqueous solution. Good linearity was observed between the peak current and concentration of carbohydrates over three orders of magnitude with detection limits (S/N = 3) ranging from 0.7 to 0.9 µM. The present system exhibited long-term stability and reproducibility with relative standard deviations of less than 5% for peak currents (n = 15). The advantages of the magnet-assembled alignment device include its simple design and construction, high alignment reproducibility, ease of operation, high degree of integration, portability and low cost. The method has been successfully applied in the determination of carbohydrates in Zingiber officinale Roscoe. Coaxially aligned copper wire and stainless steel guiding tube were enclosed between two PMMA plates by far infrared-assisted encapsulation to prepare self-positioning copper disc detection plate that was sandwiched between a magnet and a painted iron screw nut to form magnet-assembled alignment device for the amperometric detection of capillary electrophoresis.

Characterization of mannitol granules and powder: A comparative study using two flowability testers

In the manufacture of tablets, especially in direct tableting processes, the flowability of excipient powders and formulated powders is one of the most important characteristics. In the past two decades, orally disintegrating tablets (ODTs) have been prepared as popular solid dosage forms for elderly patients. Many types of mannitol granules have been developed and marketed as new pharmaceutical excipients for ODTs, owing to the solubility and palatability of mannitol. Characterizing the flow behaviors of these mannitol granules is essential to their use.The flowability of mannitol excipients was the focus of the present study. A fine crystalline mannitol powder, eight commercial types of mannitol granules and four types of mannitol mixture granules were evaluated. Two flowability testers were used for comparing and analyzing the samples’ flowabilities. A variety of methodologies were used: an assessment using Carr’s index, a shear test and a dynamic flow test. Mannitol powder showed the lowest Carr’s index, meaning the lowest flowability. Spherical mannitol granules showed the lowest angle of internal friction in the shear test and extremely low basic flow energy in the dynamic flow test. Larger granules showed relatively high values for Carr’s index, but also a relatively high total flow energy.

Nitraria sibirica cell suspension culture: establishment, characterization and application

Nitraria sibirica Pall. is a shrub that grows in saline-alkali soil and has traditional medicinal value and potential commercial value. The objectives of this study include induction and multiplication of callus, establishment of a suspension cell line, and isolation of protoplasts from cell suspensions. Murashige and Skoog (MS) medium was used for callus induction from mature seeds of N. sibirica. Seed-derived calluses were further multiplied on MS medium augmented with 0.5 mg L−1 6-benzylaminopurine (6-BA) and 1.0 mg L−1 2,4-dichlorophenoxy (2,4-D) acetic acid. Suspension cultures of N. sibirica were initiated by transferring friable calli to the same liquid multiplication medium. Characterization of the suspension culture was assessed based on fresh mass, dry mass, cell viability and pH value of the culture. A typical growth curve was observed after inoculating 1.5 g of callus in 40 mL liquid medium, including a lag phase, an exponential growth phase, a stationary phase, and a negative acceleration phase. The effect of factors such as pre-plasmolysis, enzyme combination, enzymolysis time and mannitol concentration, on the isolation of cell-derived protoplasts were evaluated to determine the usefulness of suspension cultures. The maximum yield (9.79 × 106 cells/g) and highest viability (79.97%) of protoplast were reached when approximately 1 g of cell suspension (cultured for 6 days) was inoculated for 12 h in cell and protoplast washing solution made of 0.8 mol L−1 mannitol mixture solution, cellulose onozuka R-10 2% (w/v), hemicellulose 0.2%, macerozyme R-10 1%, and pectolyase Y-23 0.5%. Protoplast yield was significantly influenced by pre-plasmolysis and cellulose onozuka R-10 (P < 0.05).

Study on dimensional stabilization of 12,500-year-old waterlogged subfossil Scots pine wood from the Koźmin Las site, Poland

Abstract The study examines the efficiency of selected conservation treatments proposed for dimensional stabilization of 12,500-year-old waterlogged subfossil Scots pine (Pinus sylvestris L.) tree trunks found at the Koźmin Las site, Poland. The research was done on 198 samples drawn from various parts of the same trunk. Experimental material was characterized on the basis of annual ring width, percentage of latewood, maximum moisture content, density at maximum moisture content, basic density, and wood porosity. Waterlogged wood samples were pre-treated with aqueous solutions of polyethylene glycol (PEG) 300, mixtures of PEG 300 and PEG 4000, a mixture of lactitol and trehalose or a mixture of mannitol and trehalose (nine variants of impregnation) and then freeze-dried or air-dried. Dimensional changes in the wood samples were measured after seasoning to reach equilibrium moisture content at 50% relative humidity and 20 °C. In the majority of the tested conservation treatments, tangential and radial shrinkages or tangential and radial swelling of wood did not exceed 1%. However, differences in dimensional changes depended on the conservation method used and sampling location. Regardless of the state of wood preservation and macroscopic structure features, the best dimensional stability, evaluated on the basis of average anti-shrink efficiency indices, was observed in wood pre-treated with aqueous solutions of 10% PEG 300 + 5% PEG 4000, 10% PEG 300 + 10% PEG 4000 or 10% lactitol/trehalose mixture, and then freeze-dried.

MCC–mannitol mixtures after roll compaction/dry granulation: percolation thresholds for ribbon microhardness and granule size distribution

In roll compaction, the specific compaction force, the gap width and the roll speed are the most important settings as they have a high impact in the products obtained. However the mechanical properties of the mixture being compacted are also critical. For this reason, a multilevel full factorial design including these parameters as factors plus three repetitions of the center point was performed for microcrystalline cellulose, mannitol and five binary mixtures (15, 30, 50, 70 and 85% MCC). These two reference excipients were chosen in order to investigate the plastic/brittle behavior of mixtures for the roll compaction process. These materials were roll compacted in a 3-W-Polygran® 250/50/3 (Gerteis) and the ribbons obtained were collected and milled into granules which were characterized regarding granule size distribution. After statistical evaluation, it was found that the most critical factors affecting the D10, D50, D90 and the fines fraction from the granules were the gap width and the specific compaction force, as well as the proportion of MCC together with its quadratic effect and the interaction between force and proportion of MCC. The microhardness of the ribbons from the center point as well as the D10, D50, D90 and the fines fraction from the granules produced at these same conditions were characterized. In all the cases, the proportion of MCC, i.e. the composition of the mixture, showed also an important effect on these properties measured. In this sense, the percolation theory was applied in order to study further the importance of the plastic/brittle ratio by calculating the percolation threshold or the limit over which the behavior of the system changes. This resulted in values of 34% for the HU (expression of microhardness), 27% and 28% for the D10 and fines, respectively (percolation of MCC) and 84% and 85% for the D50 and D90, respectively (percolation of mannitol).

Optimasi Campuran Manitol-Sukrosa Untuk Tablet Hisap Ekstrak Daun Dewa (Gynura Procumbens (Lour) Merr)) Secara Granulasi Basah Dengan Metode Simplex Lattice Design

Abstract: Dewa Leaves, Lozenges, Simplex Lattice Design. Dewa is an Indonesian traditional medicinal plants are efficacious among others to the tonsils. Dewa leaf extract can be prepared as lozenges because it is more practical and effective than the traditional way in the form of infusion. This study aimed to get the optimum formula mannitol - sucrose using the simplex lattice design that has more value than triall error. Dewa leaf aqueous extract obtained by maceration leaf powder dewa with 70% ethanol and then evaporated to obtain a thick extract is dried with aerosil. This study is based on the method simplex lattice design with two components, namely FI (100% mannitol), F II (100% sucrose), F III (50% mannitol: 50% sucrose). The method used in the manufacture of leaf extract lozenges Dewa was wet granulation using the binder PVP. The granules tested flow rate, compactibility and granules ditablet to test the taste responses. Of the value of the response characteristics of the granules obtained the largest total selected as the optimum formula. Furthermore ditablet and tested physical properties which include uniformity of weight, hardness and friability of tablets. Data of physical properties of the granules suction of the optimum formula theoretically and statistically tested using the t test (T-test). The results showed that the optimum formula derived from a mixture of mannitol 70% - sucrosa 30%. From the results of the t test (T-test) and compactibility flow rate did not different significantly betwen theoretical experiment. To test the taste responses acceptable 98% of respondents. Dewa leaf extract lozenges optimum formula produced meets the physical properties of the tablet.

Melting and solidification characteristics of a mixture of two types of latent heat storage material in a vessel

In this study, we investigated the fundamental melting and solidification characteristics of mannitol, erythritol, and their mixture (70 % by mass mannitol: 30 % by mass erythritol) as potential phase-change materials (PCMs) for latent heat thermal energy storage systems, specifically those pertaining to industrial waste heat, having temperatures in the range of 100–250 °C. The melting point of erythritol and mannitol, the melting peak temperature of their mixture, and latent heat were measured using differential scanning calorimetry. The thermal performance of the mannitol mixture was determined during melting and solidification processes, using a heat storage vessel with a pipe heat exchanger. Our results indicated phase-change (fusion) temperatures of 160 °C for mannitol and 113 and 150 °C for the mannitol mixture. Nondimensional correlation equations of the average heat transfer during the solidification process, as well as the temperature and velocity efficiencies of flowing silicon oil in the pipe and the phase-change material (PCM), were derived using several nondimensional parameters.

Dimensional changes of waterlogged archaeological hardwoods pre-treated with aqueous mixtures of lactitol/trehalose and mannitol/trehalose before freeze-drying

Abstract The article presents research on changes in the dimensions of waterlogged archaeological oak and beech wood pre-treated with aqueous solutions of either a mixture of lactitol and trehalose or a mixture of mannitol and trehalose, and then vacuum freeze-dried or dried with the use of the conventional air-drying method. Uptake of impregnants, shrinkage and moisture content in wood after freeze-drying, and changes in dimensions and moisture content in all modified and dried wood samples after its seasoning in the air at relative humidity 50% and temperature of 18 °C were determined. It was shown that even at a low uptake of lactitol/trehalose or mannitol/trehalose mixture and vacuum freeze-drying, a considerable reduction in the shrinkage of the wood under research could be obtained.

Fast dissolving fillers in dry foam formulation

Dry foam technology was developed as alternative granulation technique to overcome insufficient oral bioavailability of poorly soluble and wettable active pharmaceutical ingredients (APIs). In recent studies the type of filler showed to have a distinct influence on dry foam morphology as well as dissolution characteristics. Isomalt for instance improved the initial dissolution rate of fenofibrate dry foam formulation tablets. In this study the hypothesis that fast dissolving low molecular weight fillers improve dissolution rate and alter dry foam morphology should be confirmed with two APIs with different aqueous solubility (indomethacin, orlistat), in three different filler combinations, namely maltodextrin 21D, isomalt and 1:1 mixture of mannitol and maltodextrin 21D. In addition the dissolution behaviour of dry foam tablets was compared to fluid bed granulation formulations with the same drug loading and to an orlistat marketed formulation (Alli® 60mg capsules) in FaSSIF using USP 2 paddle apparatus and HPLC analysis after filtration.Dry foams prepared with low molecular weight fillers revealed more compact and less porous structures compared to dry foams containing maltodextrin 21D. Interestingly, their rough surface still resulted in increased surface area compared to the other formulations. The initial dissolution behaviour of indomethacin and orlistat dry foam tablets was improved by using isomalt and the mannitol–maltodextrin mixture as filler. All indomethacin formulations reached complete dissolution of the applied dose, whereas the total amount of dissolved orlistat was increased compared to the fluid bed granule tablets and the marketed formulation Alli® by using low molecular weight fillers in dry foam formulations. The improved dissolution behaviour of Orlistat dry foam tablets using low molecular weight fillers was additionally confirmed in USP monography dissolution medium.

Systematic Screening of Compressed ODT Excipients: Cellulosic Versus Non-Cellulosic

The successful development of compressed ODTs utilises low compression forces to create a porous structure whereby excipients are added to enhance wicking/swelling action or provide strength to the fragile tablet framework. In this work, a systematic investigation comparing materials from two different categories was employed to understand their functionality in binary mixture tablets of the most commonly used diluent mannitol. Cellulose based excipients such as HPC (SSL-SFP), L-HPC (NBD-022) and MCC (Avicel PH-102) were compared with non-cellulosic materials such as PEO (POLYOX WSR N-10) and Crospovidone (XL-10). Pure excipient properties were studied using Heckel Plot, compressibility profile, SEM and XRPD, whereas the prepared binary mixture compacts were studied for hardness, disintegration time and friability. Results from our investigation provide insight into differences encountered in product performance of ODT upon inclusion of additional materials. For example, non-cellulosic excipients Polyox and Crospovidone showed higher plasticity (Py values 588 and 450MPa) in pure form but not in binary mixtures of mannitol. Cellulosic excipients, nonetheless, offer faster disintegration (<30 sec) specifically L-HPC and MCC tablets. Disintegration time for tablets with fully substituted-HPC was prolonged (200-500 sec) upon increasing concentration between 1-10% due to gelation/ matrix formation. It can be concluded that despite the reasonably good plasticity of both cellulosic and noncellulosic excipients in pure form, the mechanical strength in binary mixtures is negatively impacted by the fragmentation/ fracture effect of mannitol.

Improved oral bioavailability of core–shell structured beads by redispersion of the shell-forming nanoparticles: Preparation, characterization and in vivo studies

In order to increase the dissolution rate and oral bioavailability of bifendate, coated beads with core–shell structure were prepared via a combination use of wet media milling method and bead layering process. Hydroxypropyl cellulose (HPC-SL) and sodium lauryl sulfate (SLS) were found to be the best pair to stabilize the nanosuspension during milling process. A 10:1 ratio of mixture of mannitol and SLS was chosen as most suitable coating matrix to maintain the redispersability of dried nanoparticles in the shell of beads. The mean particle size of the nanosuspension was 139nm and the zeta potential was −20.2mV. Nanoscale bifendate particles with a mean diameter of 360nm could be generated when redispersing the prepared beads in water. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analysis indicated that the crystalline state of the drug was not changed. The stability test confirmed that coated beads showed no distinct difference in particle size and dissolution velocity during 6 month storage while liquid nanosuspension was stable no more than 3 weeks. Dissolution rate of coated beads was increased significantly compared with commercially available pills. Likewise, the Cmax and AUC (0→24) of nanosuspension based beads in beagle dogs were 2.40-fold and 1.66-fold greater than that of commercially available pills, respectively. The present work is a reliable approach to stabilize nanosuspension based product, and improve dissolution velocity and bioavailability of poor soluble drugs.

Orally disintegrating tablets prepared by a co-processed mixture of micronized crospovidone and mannitol using a ball mill to improve compactibility and tablet stability

Abstract The purpose of this study was to prepare orally disintegrating tablets (ODTs) by directly compressing a mixture of sugar alcohol (mannitol) and micronized crospovidone (M-CPVP). When the mixture of mannitol and M-CPVP was co-processed by ball milling, the physicochemical properties of the resultant tablets were considerably improved, particularly their stability during storage. Several types of coground mixtures using a different ratio of M-CPVP/mannitol and processing time were tested to determine the appropriate aggregates for designing the ODTs. Without this co-processing, the powder mixture had poor compactibility, and the stability of the tablet was inferior, probably due to the high hygroscopicity of M-CPVP. The ODTs containing coground M-CPVP/mannitol showed good stability for six months under humid conditions with rapid disintegration ( 1.0 MPa). Tablet stability could not be achieved using a physical mixture of M-CPVP/mannitol without including the coground process. We also demonstrated that ODTs containing an active ingredient, acetaminophen, could be prepared using this cogrinding method.