High Resolution Determination of Ondansetron in Human Plasma by HPLC and Pharmacokinetics of Orally Disintegrating Tablets

Ahn To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets. Methods HPLC determination involved liquid-liquid extraction, separation on a CN column and ultraviolet detection at 310 ran with granisetron as an internal standard. Pharmacokinetics and bioequivalence of ondansetron in orally disintegrating tablets by direct compression and conventional 8 mg tablets were evaluated and compared in 20 healthy human male volunteers after a single oral dose in a randomized cross-over study. Results The limit of quantification was 0.25 ng· mL^-1. The recovery was about 85 % or over for ondan setron and about 90% for internal standard. Linearity was good within the concentration range of 0.5 - 50 ng·mL^-1 with r^2 ranging from 0.997 1 to 0.999 9. Intra- and inter-assay coefficients of variation ranged from 1.78% to 2.38% and 3.88% -5.19%, respectively. Accuracies for spiked concentrations of 2.0, 10.0, and 30.0 ng·mL^-1 were 104.7% ±4.4%, 102.2% ± 1.1%, and99.51% ±2.34%, respectively. Pharmacokinetic parameters of AUCo-t, AUCo-∞ , Cmax, Tmax, and T1/2 were 230.2 ± 78.0 ng·h·L^-1 , 265.2± 101.5 ng·h·mL^-1, 35.67 ± 8.94 ng·mL^-l, 1.51 ±0.79 h, and 5.00± 1.41 h for orally disintegrating tablets, respectively. The analysis of variance did not show any significant difference between orally disintegrating tablets and conventional tablets, and 90% confidence intervals fell within the acceptable range for bioequivalence. Conclusion High resolution HPLC method has been set up and applied in pharmacokinetic evaluation of ondansetron in orally disintegrating tablets.

Development and characterization of seed gums from Tamarindus indica and Cassia fistula as disintegrating agent for fast disintegrating Thai cordial tablet

Crude seed gum and their carboxymethyl derivatives from Tamarindus indica and Cassia fistula seeds were developed and characterized to apply as the pharmaceutical disintegrant in fast disintegrating Thai cordial tablet. The chemical structure of crude gum was chemically modified via carboxymethylation. Degree of substitution(DS) of carboxymethylated gums was determined. Carboxymethylated gums with minimum and maximum DS values were chosen for further application. IR absorption spectra of gum samples were observed to verify their chemical structure changes. In physical properties, the intrinsic viscosity and swelling property of all gum samples were evaluated. The results showed that carboxymethylated gums had higher intrinsic viscosity than those of crude gum. Moreover, they could swell and be soluble in cold water better than those of crude gums. In conclusion, the modified gums from both plants could provide higher hardness and be better used than that crude gums for fast disintegrating Thai cordial tablet. However, this is a preliminary assessment to expressing pharmaceutical application possibility of these gums as disintegrants, diluents and drug release controlling agents.

Formulation Study for Rotundine Rapidly Disintegrating Tablet

Aim The aim of the present study was to prepare tablets which can rapidlydisintegrate in saliva, containing active ingredient in high dose (37.5% W/W). Methods Rapidlydisintegrating tablets containing rotundine were prepared by direct compression, wet granulation andmoulding, respectively . Different disintegrants and excipients were decided by single factor test.The typical disintegration time measurement and a new method of wetting time measuring wereintroduced for assessing rapidly disintegrating tablets. Results The tablets (80 mg) prepared bydirect compression have the crushing strength of 4.0 kg ?mm^(-2) and rapidly disintegratewithin 15 s in the saliva of healthy volunteers; the tablets prepared by wet granulation also havesufficient strength, a little longer but acceptable disintegration time (within 25 s in saliva) ;and the tablets obtained by moulding show disintegration within 40 s in saliva but low strength (2kg·mm^(-2)) . Disintegration time profiles of tablets are similar to those of wetting time, and thedisintegration and wetting times in vitro are similar to the disintegration time in vivo, thelatter having higher correlation with that in oral cavity. Conclusion The rapidly disintegratingtablets can be prepared by using these three techniques and excipients. Both in vitro disintegrationtime and wetting time are necessary indexes for judgment of in vitro disintegration profile.

Predicting oral disintegrating tablet formulations by neural network techniques

Oral disintegrating tablets(ODTs) are a novel dosage form that can be dissolved on thetongue within 3 min or less especially for geriatric and pediatric patients. Current ODT for-mulation studies usually rely on the personal experience of pharmaceutical experts andtrial-and-error in the laboratory, which is inefficient and time-consuming. The aim of cur-rent research was to establish the prediction model of ODT formulations with direct com-pression process by artificial neural network(ANN) and deep neural network(DNN) tech-niques. 145 formulation data were extracted from Web of Science. All datasets were dividedinto three parts: training set(105 data), validation set(20) and testing set(20). ANN andDNN were compared for the prediction of the disintegrating time. The accuracy of the ANNmodel have reached 85.60%, 80.00% and 75.00% on the training set, validation set and testingset respectively, whereas that of the DNN model were 85.60%, 85.00% and 80.00%, respec-tively. Compared with the ANN, DNN showed the better prediction for ODT formulations.It is the first time that deep neural network with the improved dataset selection algorithmis applied to formulation prediction on small data. The proposed predictive approach couldevaluate the critical parameters about quality control of formulation, and guide researchand process development. The implementation of this prediction model could effectivelyreduce drug product development timeline and material usage, and proactively facilitatethe development of a robust drug product.

Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers

AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. METHODS: Eight H pylori-negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was perform- ed on the day of treatment. Blood samples were also collected after the administration of each drug. RESULTS: LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study. CONCLUSION: In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg.

Preparation and Characterization of Orally Fast-Disintegrating Mini-Tablets Containing Diphenhydramine Hydrochloride and Aspartic or Glutamic Acid as an Umami Amino Acid

The aim of this study was to prepare diphenhydramine hydrochloride (DPH)-loaded orally fast-disintegrating mini-tablets (OFDMTs) containing either L-aspartic acid (Asp) or L-glutamic acid (Glu) as bitterness-suppressant, to characterize the prepared tablets and to evaluate their bitterness under conditions mimicking those of the oral cavity. The preparation of five formulation batches of the OFDMTs involved mixing DPH, with or without two different concentrations of Asp or Glu, and a premix containing a disintegrating agent. When all ingredients were well mixed, the mixture was directly compacted to form small (4 mm diameter) DPH-loaded OFDMTs. There were only small differences between the tablets with respect to mass, diameter, width and hardness. The disintegration times of the five formulation batches of DPH-loaded OFDMTs were measured using the OD-mate, a disintegration test apparatus in which conditions resemble those of the oral cavity. The disintegration times were all within 10 s of exposure to a medium representing the inside of the oral cavity. Rapid release profiles were observed for DPH, Asp and Glu in these dissolution tests. The taste sensor outputs of samples taken at different times (5 - 30 s) from the dissolution test solutions of the four DPH-loaded OFDMTs containing Asp or Glu were significantly inhibited compared with those of control DPH-loaded OFDMT. These results suggest that the inclusion of Asp or Glu in DPH-loaded OFDMTs is sufficient to mask bitterness in the oral cavity for the first 30 s after the tablet is placed in the mouth. It is anticipated that swallowing will have taken place within 30 s.

PHARMACOKINETICS OF PARACETAMOL ORALLY DISINTEGRATING AND GENERAL TABLETS IN HEALTHY VOLUNTEERS

Objective To compare the pharmacokinetics and relative biological availability of Paracetatool orally disintegrating tablets and general tablets in healthy volunteers. Methods In a random two periods crossover study, 19 healthy male Chinses volunteers received a single dose of Paracetamol 500mg of two formularies respectively. The plasma concentration of paracetamol was determined by HPLC method. The pharmacokinetic parameters of the two preparation and the relative biological availability of Paracetamol orally disintegrating tablets and general tablets were caculated with statistical analysis. Results The main pharmacokinetic parameters of paracetamol orally disintegrating tablets and general tablets were （ 31436. 70 ± 7062. 80 μg · h^ -1· L^-1 and （29871.40 ± 7965.04） μg · h^ -1· L^-1 for AUC0-1 （33295. 7 ±7663. 10） μg · h^ -1· L^-1 and（31845. 20 ± 8830. 83 ） μg · h^ -1· L^-1 forAUC0-1（9. 71 ±2. 78） μg/ml and（10. 36 ±3. 86） μg/mlfor Cmax; （0. 82 ±0. 45）h and （0. 74± 0.67）hforTmax;（2.90±0. 42）h and （3. 13 ±0. 67）h for T1/2ke;（0.24 ±0.04） and （0.23 ±0.04） for Ke; （4. 1481±0. 4492 ） and （4. 0771 ±0. 8131 ） for mean residence time （ MRT） , respectively. Variance analysis showed that there was significant difference in AUC0-12 and Cmax between the two preparations. Conclusion The paracetamol orally disintegrating tablets and general tablets are bioequivalent and the relative biological availability of Paracetamol orally disintegrating tablets is （ 108 ± 19） %.

Debris falling forecast method for spacecraft disintegrating separation

Large spacecraft fall out of orbit and re-enter the atmosphere at the end of their lifetime,and they can break up into small debris upon re-entry.The spacecraft debris generated by the disintegration may lead to high risk when the surviving debris reaches the ground.One way to reduce the damage risk of spacecraft is to simulate the spacecraft disintegration process and accurately predict the falling area.Aerodynamics seriously affects the reentering process,especially in the continuous flow regime.Aerodynamic force and heat are the main factors leading to debris disintegration.High dynamic pressure leads to sharp changes in attitude and complex trajectories during debris fall.A numerical method based on an unstructured Cartesian grid was developed to simulate the disintegrating separation problem by coupling the Navier-Stokes equation and the six-degree-of-freedom trajectory equation.A method combining the numerical method for dynamic processes with numerical simulation based on a static aerodynamic/dynamic characteristic database was developed for forecasting the falling area.Spacecraft disintegrating separation from 60 km was simulated using the method,and the multibody aerodynamic interference and the separation trajectory were predicted.The falling process was forecast by a numerical simulation method based on the static aerodynamic database/dynamic characteristic database when the debris went out of the influence domain.This method has good forecasting efficiency while considering the aerodynamic interference,making it a valuable method for forecasting disintegrating separation and falling debris.

Optimization of Jiawei Qing'e Oral Fast Disintegrating Tablets Based on Response Surface-Central Composite Design

Abstract: Objective To apply the response surface-central composite design to developing and optimizing the oral fastdisintegrating tablets (ODT) formulation for Jiawei Qing’e, a kind of prescription of Chinese herbal medicine.Methods The bitterness of Jiawei Qing’e was masked using Eudragit E-100 by solvent evaporation technique.Response surface approach was applied to investigating the interaction of formulation parameters in optimizing theformulation. The independent variables were Eudragit E-100/drug ratio (X1), amount of disintegrants (X2), and theamount of diluents (X3). The disintegration time (Y1), hardness (Y2), and weight variations of the tablets werecharacterized. Results The models predicted levels of X1= 4.63%, X2= 5.25%, and X3= 34.33%, for the optimalformulation having a hardness of 3.0 kg with the disintegration time of 30 s within experimental region. The observedresponse of Y1= 26.5 s and Y2= 3.14 kg reasonably agreed with the predicted response. Conclusion Responsesurface methodology shows the good predictability and reliability in optimizing the formulation. The optimized ODTof Jiawei Qing’e has acceptable taste, rapid disintegrating ability, and good mechanical strength.

Influencer identification of dynamical networks based on an information entropy dimension reduction method

Identifying critical nodes or sets in large-scale networks is a fundamental scientific problem and one of the key research directions in the fields of data mining and network science when implementing network attacks, defense, repair and control.Traditional methods usually begin from the centrality, node location or the impact on the largest connected component after node destruction, mainly based on the network structure.However, these algorithms do not consider network state changes.We applied a model that combines a random connectivity matrix and minimal low-dimensional structures to represent network connectivity.By using mean field theory and information entropy to calculate node activity,we calculated the overlap between the random parts and fixed low-dimensional parts to quantify the influence of node impact on network state changes and ranked them by importance.We applied this algorithm and the proposed importance algorithm to the overall analysis and stratified analysis of the C.elegans neural network.We observed a change in the critical entropy of the network state and by utilizing the proposed method we can calculate the nodes that indirectly affect muscle cells through neural layers.

Impact of wetting-drying cycles and acidic conditions on the soil aggregate stability of yellow‒brown soil

Soil aggregate is the basic structural unit of soil,which is the foundation for supporting ecosystem functions,while its composition and stability is significantly affected by the external environment.This study was conducted to explore the effect of external environment(wetting-drying cycles and acidic conditions)on the soil aggregate distribution and stability and identify the key soil physicochemical factors that affect the soil aggregate stability.The yellow‒brown soil from the Three Gorges Reservoir area(TGRA)was used,and 8 wetting-drying conditions(0,1,2,3,4,5,10 and 15 cycles)were simulated under 4 acidic conditions(pH=3,4,5 and 7).The particle size distribution and soil aggregate stability were determined by wet sieving method,the contribution of environmental factors(acid condition,wetting-drying cycle and their combined action)to the soil aggregate stability was clarified and the key soil physicochemical factors that affect the soil aggregate stability under wetting-drying cycles and acidic conditions were determined by using the Pearson’s correlation analysis,Partial least squares path modeling(PLS‒PM)and multiple linear regression analysis.The results indicate that wetting-drying cycles and acidic conditions have significant effects on the stability of soil aggregates,the soil aggregate stability gradually decreases with increasing number of wetting-drying cycles and it obviously decreases with the increase of acidity.Moreover,the combination of wetting-drying cycles and acidic conditions aggravate the reduction in the soil aggregate stability.The wetting-drying cycles,acidic conditions and their combined effect imposes significant impact on the soil aggregate stability,and the wetting-drying cycles exert the greatest influence.The soil aggregate stability is significantly correlated with the pH,Ca^(2+),Mg^(2+),maximum disintegration index(MDI)and soil bulk density(SBD).The PLS‒PM and multiple linear regression analysis further reveal that the soil aggregate stability is primarily influenced by SBD,Ca^(2+),and MDI.These results offer a scientific basis for understanding the soil aggregate breakdown mechanism and are helpful for clarifying the coupled effect of wetting-drying cycles and acid rain on terrestrial ecosystems in the TGRA.

Classification and rating of disintegrated dolomite strata for slope stability analysis

Although disintegrated dolomite,widely distributed across the globe,has conventionally been a focus of research in underground engineering,the issue of slope stability issues in disintegrated dolomite strata is gaining increasing prominence.This is primarily due to their unique properties,including low strength and loose structure.Current methods for evaluating slope stability,such as basic quality(BQ)and slope stability probability classification(SSPC),do not adequately account for the poor integrity and structural fragmentation characteristic of disintegrated dolomite.To address this challenge,an analysis of the applicability of the limit equilibrium method(LEM),BQ,and SSPC methods was conducted on eight disintegrated dolomite slopes located in Baoshan,Southwest China.However,conflicting results were obtained.Therefore,this paper introduces a novel method,SMRDDS,to provide rapid and accurate assessment of disintegrated dolomite slope stability.This method incorporates parameters such as disintegrated grade,joint state,groundwater conditions,and excavation methods.The findings reveal that six slopes exhibit stability,while two are considered partially unstable.Notably,the proposed method demonstrates a closer match with the actual conditions and is more time-efficient compared with the BQ and SSPC methods.However,due to the limited research on disintegrated dolomite slopes,the results of the SMRDDS method tend to be conservative as a safety precaution.In conclusion,the SMRDDS method can quickly evaluate the current situation of disintegrated dolomite slopes in the field.This contributes significantly to disaster risk reduction for disintegrated dolomite slopes.

Complex systems and network science:a survey

Complex systems widely exist in nature and human society.There are complex interactions between system elements in a complex system,and systems show complex features at the macro level,such as emergence,self-organization,uncertainty,and dynamics.These complex features make it difficult to understand the internal operation mechanism of complex systems.Networked modeling of complex systems is a favorable means of understanding complex systems.It not only represents complex interactions but also reflects essential attributes of complex systems.This paper summarizes the research progress of complex systems modeling and analysis from the perspective of network science,including networked modeling,vital node analysis,network invulnerability analysis,network disintegration analysis,resilience analysis,complex network link prediction,and the attacker-defender game in complex networks.In addition,this paper presents some points of view on the trend and focus of future research on network analysis of complex systems.

SNCDM: Spinal Tumor Detection from MRI Images Using Optimized Super-Pixel Segmentation

Conferring to the American Association of Neurological Surgeons(AANS)survey,85%to 99%of people are affected by spinal cord tumors.The symptoms are varied depending on the tumor’s location and size.Up-to-the-min-ute,back pain is one of the essential symptoms,but it does not have a specific symptom to recognize at the earlier stage.Numerous significant research studies have been conducted to improve spine tumor recognition accuracy.Nevertheless,the traditional systems are consuming high time to extract the specific region and features.Improper identification of the tumor region affects the predictive tumor rate and causes the maximum error-classification problem.Consequently,in this work,Super-pixel analytics Numerical Characteristics Disintegration Model(SNCDM)is used to segment the tumor affected region.Estimating the super-pix-els of the affected region by this method reduces the variance between the iden-tified pixels.Further,the super-pixels are selected according to the optimized convolution network that effectively extracts the vertebral super-pixels features.Derived super-pixels improve the network learning and training process,which minimizes the maximum error classification problem also the efficiency of the system was evaluated using experimental results and analysis.

Mechanical stirring for highly efficient gas injection refining

In gas injection refining processes,wide dispersion of small bubbles in the bath is indispensable for high refining efficiency.Eccentric mechanical stirring with unidirectional impeller rotation was tested using a water model for pursuing better bubble disintegration and dispersion.Effects of various factors on bubble disintegration and dispersion were investigated.These factors were stirring mode,eccentricity and rotation speed,nozzle structure,nozzle immersion depth,and gas flow rate.Gas injection from a nozzle at the end of the impeller shaft and from an immersed lance was studied.Under eccentric stirring,a vortex was formed away from the shaft.Small bubbles were produced in the strong turbulence or high shear stress field near the rotating impeller and moved in the direction to the vortex keeping up with the macroscopic flow induced by the mechanical stirring.Thus small bubbles could disperse widely in the bath under eccentric stirring with unidirectional rotation.

Usefulness and limitations of taste sensors in the evaluation of palatability and taste-masking in oral dosage forms

The purpose of this review is to discuss the advantages and limitations of taste sensors in the evaluation of the taste of palatability of different oral dosage forms. First, we consider some ways in which the palatability of various pharmaceutical formulations including orally disintegrating tablets(ODTs) are tested using two different taste sensors. Second, we focus on the evaluation of palatability of ODTs. We compare the usefulness of three pieces of apparatus for estimating the disintegration time of ODTs. Finally, we compare the characteristics of the two taste sensors in the evaluation of palatability of various kinds of drug formulations.

The comprehensive utilization of Baosteel steel slag

Summarizes the processes and development of Baosteel slag processing techniques such as the instantaneous slag chill （ISC） process, the tank-type hot disintegrating process and the rotary drum process. A detailed introduction of the slag comprehensive utilization at Baosteel is given. The details of Baosteel＇ s comprehensive utilization in the fields of simering materials, returned slag for steelmaking, road construction, cement production, mixed concrete, new construction materials, ground-filling materials and reinforced material for soft earth are given. Emphasis is placed on source management and ensuring that from both organizational and managerial perspectives, Baosteel＇ s slag processing techniques are safe and energy-saving, thus constantly demonstrating the issue of sustainable development.

The Effect of Food Thickeners on the Bitterness and Dissolution of Amlodipine Besilate Loaded Oral Disintegration Tablets: Assessment of Potential Suitability for Patients with Dysphagia

The purpose of this research was to evaluate the effect of starch- and xanthan gum-based food thickeners on the bitterness and dissolution of amlodipine besilate (AMPB) loaded orally disintegrating tablets (ODT) for potential use with patients with dysphagia. A conventional dissolution test simulating the oral cavity was performed and the taste sensor output of the dissolved sample was evaluated over a 60-seconds period. When four types of AMPB loaded ODTs were tested alone, at 60 seconds, branded product (A) was the least bitter, followed by generic product (B)/generic product (C) which were equal, and finally generic product (D) which was the most bitter. Inhibition of bitterness of AMPB loaded ODTs mixed thickeners, 1.0 (w/v) % xanthan gum-based food thickener solution was significantly strong. The 7.1 (w/v) % and 4.7 (w/v) % starch-based food thickeners solution also effective in bitterness inhibition compared to the 2.4 (w/v) % starch-based food thickener solution. The dissolution test under pH 1.2 in related to 7.1 (w/v) % and 4.7 (w/v) % starch-based thickener contained each of AMPB loaded ODTs were associated with an almost complete amlodipine (AMP) dissolution (almost 90% at 10 minutes), whereas the 1.0, 2.0, 3.0 (w/v) % xanthan gum-based food thickener solution containing AMPB loaded ODTs did not show complete AMP dissolution and there were large variations in the initial dissolution stage. This suggests that a mixture of xanthan gum-based thickener and AMPB loaded ODT poses a risk of reduction of bioavailability. In conclusion, a mixture of 4.7 (w/v) % or 7.1 (w/v) % starch-based thickener with ODTs provides complete release of AMP and superior bitterness inhibition, so is the best choice for administration to patients with dysphagia.

Evaluation of the quality of olanzapine orally disintegrated tablets by multiple dissolution curves

Objective: To investigate the dissolution behavior similarity between Self-made praeparatum and reference praeparatum in different pH menstruum,using the Olanzapine Orally Disintegrating Tablets listed in abroad as the reference praeparatum. Methods: The dissolution curve of olanzapine in Self-made praeparatum and reference praeparatum was measured,the similarity of the dissolution curve was evalued by F2 similar factor. Results: The single-point dissolution of both Self-made praeparatum and reference praeparatum within 15 min was more than 85%. Conclusion: Self-made praeparatum and reference praeparatum were similar in dissolution behavior.

ZONAL DISINTEGRATION MECHANISM OF DEEP CRACK-WEAKENED ROCK MASSES UNDER DYNAMIC UNLOADING

Size and quantity of fractured zone and non-fractured zone are controlled by cracks contained in deep rock masses. Zonal disintegration mechanism is strongly dependent on the interaction among cracks. The strong interaction among cracks is investigated using stress superposition principle and the Chebyshev polynomials expansion of the pseudo-traction. It is found from numerical results that crack nucleation, growth and coalescence lead to failure of deep crack- weakened rock masses. The stress redistribution around the surrounding rock mass induced by unloading excavation is studied. The effect of the excavation time on nucleation, growth, interaction and coalescence of cracks was analyzed. Moreover, the influence of the excavation time on the size and quantity of fractured zone and non-fractured zone was given. When the excavation time is short, zonal disintegration phenomenon may occur in deep rock masses. It is shown from numerical results that the size and quantity of fractured zone increase with decreasing excavation time, and the size and quantity of fractured zone increase with the increasing value of in-situ geostress.