Dissolution Calculation Software Free Download

1. Sigmaplot 14 Free Download With Crack
2. Dissolution F2 Calculation

Visual MINTEQ is a freeware chemical equilibrium model for the calculation of metal speciation, solubility equilibria, sorption etc. For natural waters. It combines state-of-the-art descriptions of sorption and complexation reactions with easy-to-use menus and options for importing and exporting data to/from Excel. Chemical equilibrium modelling has never been easier!The code, originally built on USEPA’s software, is maintained by at KTH, Sweden, since 2000.Visual MINTEQ will run on most Windows platforms and relies on.NET Framework. For more details,. Posted on November 27, 2013 March 7, 2017Version 3 represents a major new release. The interface code has been completely rewritten in VB.NET.

The download and installation procedures have changed, and a number of new options has also been introduced. The help file has been updated, and a new user guide is being written; a draft, still not yet complete, is included in the download. Below there is a list of all major changes compared to version 2.6:Installer and file locations. Version 3 comes with a different installer, which should (in most cases) work more reliably than the old installer. The default location of the downloaded files is in the Program Files folder. When starting the application for the first time, the user will be asked where he/her would like to have the user-editable files located.

The default location is in the My Documents folder.Species tableau. A new table presents the species added to the problem in the form of a tableau, which includes information on the stoichiometry, log K and reaction enthalpy of each species. This tableau is accessible from the component list page.Option to add a component as an element. A frequently asked question from users has been why it has not been possible to add, for example, arsenate as As(V) (i.e. As arsenic, with a molecular weight as for elemental As) rather than as AsO4 -3, which is the standard component for As(V).

This is now possible. It means, for example, that you can import As(V) data from Excel when data are given in ug/l As. Previously you had to recalculate such data to a molar unit before Excel import.More flexibility for predefined adsorption models. On page 2 of the default parameters menu (accessible from Parameters – Various default settings), users can now define their own parameter sets for surface complexation models (SCM:s). This greatly facilitates parameter input when you are working with any other SCM parameter sets than those included in the download package. The parameter sets are saved as a special text file, ‘admodel.txt’, so that the parameter sets can be shared easily between different users.Different functionality of the adsorption isotherms. The adsorption isotherms remained an underdeveloped part of the 2.xx versions of Visual MINTEQ. It was possible to define many isotherms, but with the important restriction that the dissolved entity of the adsorbate had to be supplied as its free ion activity. Commonly, however, adsorption isotherms are defined using the total dissolved concentration of the adsorbate.

From version 3.0, only the linear Kd and Freundlich-type models are included in Visual MINTEQ. For these models it is possible to choose between the free ion activity and the total dissolved concentration as the basis of the calculations.Saturation indexes for minerals in sweep problems. It is now possible to choose to have the saturation indexes of different minerals listed in the sweep output file. Posted on November 27, 2013 December 21, 2013Visual MINTEQ can simulate the chemical composition in solutions in contact with gases, solid compounds and particle surfaces.

In recent years, several mathematical models have been developed for analysis of drug dissolution data, and many different mathematical approaches have been proposed to assess the similarity between two drug dissolution profiles. However, until now, no computer program has been reported for simplifying the calculations involved in the modeling and comparison of dissolution profiles. The purposes of this article are: (1) to describe the development of a software program, called DDSolver, for facilitating the assessment of similarity between drug dissolution data; (2) to establish a model library for fitting dissolution data using a nonlinear optimization method; and (3) to provide a brief review of available approaches for comparing drug dissolution profiles. DDSolver is a freely available program which is capable of performing most existing techniques for comparing drug release data, including exploratory data analysis, univariate ANOVA, ratio test procedures, the difference factor f 1, the similarity factor f 2, the Rescigno indices, the 90% confidence interval (CI) of difference method, the multivariate statistical distance method, the model-dependent method, the bootstrap f 2 method, and Chow and Ki’s time series method. Sample runs of the program demonstrated that the results were satisfactory, and DDSolver could be served as a useful tool for dissolution data analysis. INTRODUCTIONIn vitro dissolution testing plays an important role in drug formulation development and quality control.

It can be used not only as a primary tool to monitor the consistency and stability of drug products but also as a relatively rapid and inexpensive technique to predict in vivo absorption of a drug formulation. Therefore, quantitative evaluation of drug dissolution characteristics is of great interest to pharmaceutical scientists.A wide variety of mathematical models have been developed to fit the drug release data, most of which are presented as nonlinear equations. Because there is no available computer program for fitting drug release data using these specific nonlinear equations, it is desirable to develop a nonlinear fitting program for solving these problems in a convenient way. However, until now, only one special program has been reported for fitting dissolution data, and only five release models have been implemented, and these could be applied only over a limited range.

Alternatively, the nonlinear fitting of dissolution data can be performed using other professional statistical software packages such as MicroMath Scientist , GraphPad Prism , SigmaPlot , or SYSTAT. However, these programs require the user to define the equation manually and to provide an initial value for each parameter. This may make it difficult for new users to implement the procedure. Therefore, it is necessary to investigate an easy-to-use program for fitting release data with more ready-to-use dissolution models.Another important area in dissolution data analysis is assessment of the similarity between dissolution profiles. Several approaches have been developed for comparing dissolution profiles, including approaches using the difference factor f 1 and the similarity factor f 2 , the Rescigno indices approaches , ratio-test approaches , ANOVA-based approaches , multivariate statistical approaches , and model-dependent approaches. It can be seen that the mathematical theory in this field has been well developed for more than 10 years. However, to the authors’ knowledge, no computer software package has been developed to facilitate calculations in this field; therefore, data analysis can be done only by hand or be partially done by professional statistical programs.

This is time-consuming, and transcription errors are a common problem. Therefore, it is worthwhile to explore a program to streamline these tasks.This paper presents a versatile and freely available add-in program, called DDSolver, which can be used (1) to facilitate the modeling of dissolution data using nonlinear optimization methods based on a built-in model library containing forty dissolution models, (2) to simplify the task of assessing the similarity between dissolution profiles using various popular approaches, and (3) to speed up the calculation, reduce user errors, and provide a convenient way to report dissolution data quickly and easily. The aim of this article is to report on the development of the specialized program for analysis of dissolution data. InterfaceDDSolver is a menu-driven add-in program for Microsoft Excel written in Visual Basic for Applications. Calculation using Excel offers a number of advantages over other software packages, the most attractive of which is ease of use. Most scientists are already familiar with Excel because of its wide availability and high flexibility. As shown in Fig., after the program has been installed, a pull-down menu called DDSolver will appear on the menu bar when Excel is launched.

Users can choose any module by clicking on the item in the pull-down menu and can input dissolution data by simple drag selection of the corresponding range of cells in the spreadsheet, as shown in Fig. DDSolver provides a range of customizable options for each module, such as convergence and maximum number of iterations of the nonlinear optimization algorithm, initial parameter estimates, number of decimal places in the calculated results, chart output, and Microsoft Word report generation.

In addition, a built-in sample dataset can be loaded by clicking on the sample button in each module. This is provided as a guide for new users to help them arrange their data into a suitable form for processing by the program. Drug Dissolution ModelsSince the development of the Higuchi equation in 1961 , numerous mathematical models have been proposed for quantitative evaluation of in vitro drug release behavior. This work was not performed to assess any particular model or to discuss the statistical or mechanical meaning of each model parameter, because these topics have been well reviewed previously (,). In fact, this work was intended to establish a model library and to assemble it into a ready-to-use module which can be easily accessed through the DDSolver program. For this purpose, a wide range of dissolution models was collected. Table summarizes all the models implemented in the program; in all cases, F is the percentage of drug released at time t.

Once the model library has been established, the release data can be easily fitted to any available model followed by quick generation of scatter plots with fitted curves for each individual dataset and a scatter plot with error bars and fitted curves for average data. Where n is the number of observations, w i is the weighting factor, which can be optionally set as 1, 1/ y iobs or 1/ y iobs 2 for fitting dissolution data, y iobs is the ith observed y value, and y ipre is the ith predicted y value. To minimize the objective function SS or WSS and to find the best parameters, one of the most robust minimization algorithms, the Nelder–Mead simplex algorithm, was used. This method is a popular, computationally compact, and often effective method for nonlinear optimization.

Initial ParametersAn initial value for each parameter in the equation must be provided before performing the iterative optimization. A good guess for the initial values will result in fast convergence and markedly reduce the possibility of falling into a local minimum.

DDSolver provides a number of methods for obtaining appropriate initial values, including simple linear regression, multiple linear regression, trial and error, the empirical method, and various combinations of these. For model equations that can be rearranged into a linear form, the simple linear regression method is preferred. It is an effective way to obtain appropriate initial values for most dissolution models. Take the first-order model, for example; its equation is, which can be rearranged into the form, from which an initial value of k 1 can be easily estimated by fitting a linear equation with intercept zero to the transformed data.However, in cases where linear transformation of the model equation produces multiple line segments, the multiple linear regression method should be used.

The Makoid–Banakar model with a rearranged model equation, is a case of this type. The trial-and-error method is used for assessing the initial values of parameters when the Hopfenberg model is used, whose model equation is, which cannot be linearized before the parameter n is determined.

In this case, DDSolver will use n = 1 and a corresponding value of k HB which is subsequently estimated by simple linear regression during the first trial to obtain a value of WSS. Then, n = 2 and n = 3 will be used for the second and the third trials, with the pair of n and k HB values which produces the smallest value of WSS serving as the most appropriate initial values.The empirical method is another effective way for obtaining initial values when the model equation cannot be linearly transformed. For example, when the Peppas–Sahlin model with equation is used, DDSolver will suggest an empirical value of 0.45 as the initial value of m, because m lies within the range from 0 to 1 in most cases. Besides the methods mentioned above, DDSolver also allows the user to specify an initial value for each parameter manually. Model Selection CriteriaThe selection of a suitable model for fitting dissolution data is essential, not only for quantitative evaluation of drug release characteristics but also for comparison of dissolution profiles using model-dependent approaches. DDSolver provides a number of statistical criteria for evaluating the goodness of fit of a model, including the correlation coefficient ( Robs–pre), the coefficient of determination (Rsqr, R 2, or COD), the adjusted coefficient of determination (Rsqradj or R 2 adjusted), the mean square error (MSE), the standard deviation of the residuals (MSEroot or Sy.x), SS, WSS, the Akaike Information Criterion (AIC), and the Model Selection Criterion (MSC).

Among these criteria, the most popular ones in the field of dissolution model identification are the R 2 adjusted, the AIC , and the MSC.For release models with the same number of parameters, the coefficient of determination ( R 2) can be used to discriminate the most appropriate model. However, when comparing models with different numbers of parameters, the adjusted coefficient of determination should be used.

Where n is the number of data points and p is the number of parameters in the model. This is because R 2 will always increase as more parameters are included, whereas R 2 adjusted may decrease when over-fitting has occurred. Therefore, the best model should be the one with the highest R 2 adjusted, rather than that with the highest R 2.The Akaike Information Criterion has been used for selecting optimal models for more than 35 years. Its general applicability and simplicity make it an excellent and popular criterion for various purposes, including drug dissolution data analysis. The AIC as defined below is dependent on the magnitude of the data as well as the number of data points. Where n is the number of data points, WSS is the weighted sum of squares, and p is the number of parameters in the model.

When comparing two models with different numbers of parameters, the model with a lower AIC value can be considered to be the better model, but how much lower the value needs to be to make the difference between the models statistically significant cannot be determined because the distribution of the AIC values is unknown. It should be noted that when a comparison is made, the weighting scheme used in each model must be the same.The MSC provided by MicroMath Corporation is another statistical criterion for model selection which is attracting increasing attention in the field of dissolution data modeling (,); it is defined as. Where w i is the weighting factor, which is usually equal to 1 for fitting dissolution data, y iobs is the ith observed y value, y ipre is the ith predicted y value, is the mean of all observed y-data points, p is the number of parameters in the model, and n is the number of data points. The MSC is a modified reciprocal form of the AIC and has been normalized so that it is independent of the scaling of the data points. When comparing different models, the most appropriate model will be that with the largest MSC.

Sigmaplot 14 Free Download With Crack

It is, therefore, quite easy to develop a feeling for what the MSC means in terms of how well the model fits the data. Generally, a MSC value of more than two to three indicates a good fit.Although all the criteria mentioned above can be calculated by DDSolver to assess the goodness of fit of dissolution models, it should be noted that when mechanistic models are evaluated, model selection should be based, not only on the goodness of fit but also on the mechanistic plausibility of the model. More detailed discussions on the difference between mechanism-based models and empirical mathematical models can be found in previous reports (,). Dissolution Profile ComparisonDuring the past decade, several approaches have been proposed for assessing the similarity between dissolution profiles. As shown in Table, DDSolver implements most of the widely used methods, especially those recommended by the FDA. To give readers an intimate knowledge of these methods and to provide an explanation of the output results of the program, a brief review of these methods, as well as the advantages and disadvantages of each method, is presented in this section.

Dissolution F2 Calculation

Due to the limitation on the length of this paper, the contents are provided in the supplementary material to this article. Other Dissolution FunctionsOne of the distinctive features of DDSolver is the implementation of eight user-defined functions for characterizing drug release curves as shown in Table and 11 user-defined functions for evaluating the similarity between dissolution profiles as shown in Table. All the parameters of these functions are calculated using a model-independent nonparametric method based on the linear trapezoidal rule. These functions can be conveniently used in the same way as SUM or other built-in functions in Microsoft Excel. Figure shows a sample sheet with a full application of all the dissolution functions. It should be noted that most of the parameters can be alternatively calculated using a model-dependent method.

Abbreviation, descriptionEquationFunction in DDSolverReference(s)AUC, area under the dissolution curveDDAUCABC, area between the drug dissolution curve and its asymptoteDDABC(,)MRT, mean residence time of the drug substance molecules in the dosage formDDMRTMDT, mean dissolution timeDDMDT(,)VDT, variance of dissolution timeDDVDT(,)m k, moments of dissolution times of order kDDMDTk(,)RD, relative dispersion of dissolution time, CV 2 (coefficient of variation)DDRD(,)DE, dissolution efficiencyDDDE. Abbreviation, descriptionEquationFunction in DDSolverReference(s)f 1, difference factor aDDf1f 2, similarity factor aDDf2f 1’, difference factor modified by Costa P. ADDf1cpξ 1, first-order Rescigno index a, bDDres1ξ 2, second-order Rescigno index a, bDDres2S d, difference in similarity cDDSdD, sum of squared mean differences dDDD(,)D 1, mean distance dDDD1(,)D 2, mean squared distance dDDD2D AUC, difference of area under the profiles d, eDDDAUCD ABC, area between the profiles d, eDDDABC. A R t, T t are the percentage dissolved of the reference and test profile, respectively, at time point t; n is the number of sampling pointsb j is 1 and 2 for the first- ( ξ 1) and second-order ( ξ 2) Rescigno indexes, respectivelyc n is the number of sampling points; AUC Rt and AUC Tt are the areas under the dissolution curves of the reference and test formulations, respectively, at time td p is the number of sampling points; and are the mean dissolution values of the test and reference profiles respectively at the ith time pointe t i is the ith sampling time point. RESULTS AND DISCUSSIONValidation of a newly developed program is an important aspect of its acceptability. For this purpose, some typical modules of the DDSolver program were evaluated using previously published data.

Because of the limitation on the length of this paper, the results have been provided in the supplementary material to this article. Sample runs were performed using one module for dissolution-model fitting using the Weibull model and five modules for comparison of dissolution profiles using f 1, f 2, the Rescigno index ξ 1, the Rescigno index ξ 2, the multivariate-confidence-region method, and Chow and Ki’s time series method.As summarized in Table, the results indicated that all the parameters calculated, using DDSolver, were identical to those given in previous reports.

It should be noted that slight numerical differences between the estimates of DDSolver and those of previous reports were observed when the Weibull model was used to fit the dissolution data. This might be because different tolerance and convergence settings and optimization strategies were adopted. CONCLUSIONSThe DDSolver program was developed to facilitate the modeling and comparison of drug dissolution data. The program can fit drug release data using nonlinear optimization techniques in an easy-to-use spreadsheet environment.

It is the first reported program which is specifically designed to assess the similarity between dissolution profiles. The program is capable of performing most existing techniques for comparing drug release data, including exploratory data analysis, univariate ANOVA, ratio test procedures, the difference factor f 1, the similarity factor f 2, the Rescigno indices, the 90% CI of difference method, the multivariate statistical distance method, the model-dependent method, the bootstrap f 2 method, and Chow and Ki’s time series method. In addition, several user-defined functions for characterizing drug-release curves and for assessing the similarity between dissolution profiles are also implemented in the program.

These additional functions can be conveniently used in the same way as the built-in functions in Microsoft Excel. Sample runs of the program demonstrated that DDSolver can be considered a reliable program for dissolution data analysis.The DDSolver program is freely available.

The interested reader can obtain the program from the supplementary material to this article. The program was developed and tested in Microsoft Excel 2003 (both English and Simplified Chinese versions) in a Windows XP SP2 environment and was compatible with Microsoft Excel 2007 and 2010 on Windows platform.