NPK Method Research Articles

Thermal stability, preformulation, and kinetic degradation studies for gestrinone

AbstractGestrinone is an active pharmaceutical ingredient used in the treatment of endometriosis as capsules, with ongoing evaluation for intravaginal administration, while also having been studied for its potential antitumoral effects. The purpose of this study was to determine the compatibility of gestrinone with four excipients used in the development of solid pharmaceutical formulations (α-lactose monohydrate, magnesium stearate, starch, and talc) and to obtain a fully characterized thermoanalytical profile of gestrinone with the help of kinetic analysis. Preformulation studies were carried out on 1:1 mass/mass binary mixtures between gestrinone and each excipient by instrumental screening under ambient conditions using ATR-FTIR spectroscopy investigations, and later by studying the effect of thermal treatment over the samples (TG/DTG/DSC). The obtained results suggest that under ambient conditions, no chemical interactions take place between the active pharmaceutical ingredient and selected excipients, whereas under thermal stress incompatibilities are observed in all systems. The mechanism of decomposition was preliminary evaluated by the ASTM E698 and later completed by the isoconversional methods of Friedman, Kissinger–Akahira–Sunose, and Flynn–Wall–Ozawa, which suggest similar mean activation energies. The mechanism of decomposition was elucidated in the last part of the study, by employing the modified NPK method. This method suggests that gestrinone is thermally degraded by the contribution of two individual processes, both consisting of superimposed physical transformations and chemical degradations.

Determination of crystallization kinetics of the polyethylene with the NPK method

Determination of crystallization kinetics of the polyethylene with the NPK method

IMPACT OF DIFFERENT NPK LEVELS AND SOWING METHODS ON MAIZE GROWTH, YIELD, AND QUALITY CHARACTERISTICS

Crop management practices are crucially important to increased yield and quality. This research study was planned to investigate the effects of different levels of NPK and sowing methods on maize. Results showed that different NPK levels and sowing methods significantly affected the growth and yield traits of maize (p<0.05). The better results for plant height (cm), leaf area index, cob length (cm), grains per cob, 1000-grain weight, grain yield (kg ha-1), protein content (%) total sugars (%) and starch (%) were recorded when crop-fertilized NPK with 150-120-120 kg ha-1. However, all these parameters were marginally different compared to NPK rate of 120-90-90 kg ha-1, except for plant height (cm). This treatment produced significantly higher grain yield and quality traits of maize compared to lower and control treatment. Minimum values for plant height (cm), leaf area index, cob length (cm), grains per cob, 1000-grain weight, grain yield kg ha-1, protein content (%), total sugars (%) and starch (%) were noted in the control treatment. In case of sowing methods, ridge sowing produced maximum plant height (cm) , leaf area index, 50% days to tasselling and yield contributing characters like cob length (cm), grains cob-1, 1000-grain weight (g) and grain yield (kg ha-1) of maize as compared to broadcasting and drilling sowing methods. But sowing methods did not significantly affected the quality characteristics of maize, particularly protein content (%), total sugars (%) and starch (%). Among different sowing methods, ridge sowing method produced the maximum grain yield kg ha-1 of maize as compared to drilling and broadcasting. Considering the results comprehensively, the NPK rate of 120-90-90 kg ha-1 under ridge method would be the best management practice for maize cultivation:

Determination of polymer crystallization kinetics with the NPK method

Determination of polymer crystallization kinetics with the NPK method

Study of kinetic characteristics of 6-ethyl chenodeoxycholic acid and deoxycholic acid decomposition in non-isothermal conditions

6-ethyl chenodeoxycholic acid (6ECDA) and deoxycholic acid (DCA) are two similar-structured cholanoic acids, the first being used in the treatment of primary biliary cholangitis, while the second is one of the natural secondary bile acids, currently being tested as a treatment component in the destruction of gallstones. This study was realised as no literature reference was found over thermal behaviour and the evaluation of the decomposition kinetics of the compounds from this class. Both acids were characterised by UATR-FTIR spectroscopy, thermal analysis and the kinetics of decomposition in dynamic oxidative atmosphere, by employing three isoconversional methods, namely Friedman, Kissinger–Akahira–Sunose and Flynn–Wall–Ozawa, respectively, the modified NPK method. Isoconversional methods suggested that no modification of the decomposition mechanism occurs with the modification of thermal treatment of the samples. Later, the modified NPK method was employed in order to estimate the kinetic triplet that describes the decomposition process of both compounds. All kinetic methods indicate a very good thermal stability of the bile acids, with apparent activation energies between 190.6 and 208.7 kJ mol−1 for the decomposition of 6ECDA and 205.5 and 221.7 kJ mol−1 for the decomposition of CDA, respectively. The modified NPK method suggested that both bile acids are degraded by the contribution of two distinctive chemical processes without any physical process associated.

Kinetics of heterogeneous-induced degradation for artesunate and artemether

This paper presents the results obtained after the investigation of two artemisinin derived sesquiterpenes, namely artesunate and artemether, currently studied for their antitumor properties. The chosen methods of analysis included UATR–FTIR spectroscopy, characterization of the thermal behavior (TG/DTG/HF) in oxidative dynamic atmosphere, and a complete kinetic analysis. The latter was realized using two integral methods (Kissinger–Akahira–Sunose and Flynn–Wall–Ozawa), a differential one (Friedman), and was later completed with the modified NPK method. The study showed that both compounds show similar thermal stability in terms of apparent activation energies and the degradation processes occur in two parallel steps for each compound, this being solely due to chemical transformations.

Processing of hydrogel isotermic data on the base of polymethyl vinyl ether of maleic acid cross linked with polypropylene glycol under thermogravimetric data Comparative kinetic analysis by NPK method

Processing of hydrogel isotermic data on the base of polymethyl vinyl ether of maleic acid cross linked with polypropylene glycol under thermogravimetric data Comparative kinetic analysis by NPK method

Thermal behavior and kinetic study of degradation for adamantan-2-one versus memantine hydrochloride

Adamantan-2-one is an adamantane derivative used as a precursor for different adamantane-based pharmacologically active compounds. Adamantan-2-one and memantine hydrochloride were investigated in other of our previous published papers, as pure compounds and in binary mixtures with various excipients. The aim of our study is to determine the thermal behavior of adamantan-2-one, as well as the kinetic parameters that characterize the degradation process of this precursor. The employed analytical techniques were thermal analysis (TG/DTG/HF) and FTIR spectroscopy. The TG/DTG/HF curves were recorded in air at different heating rates: β = 5, 7, 10, 12 and 15 °C min−1, in respect of the ICTAC 2000 protocol regarding the kinetic analysis. The methods used for kinetic analysis of the thermal degradation process were isoconversional methods: Friedman and Flynn–Wall–Ozawa. Modified NPK method was used for determination of kinetic parameters.

An extension of the NPK method to include the pressure dependency of solid state reactions

An novel method to identify the pressure dependency for reactions of the type A(s)⇌B(s)+C(g) is proposed. It is an extension of the non-parametric kinetic analysis (NPK) method as it identifies the pressure dependency in addition to the temperature and conversion dependency of the reaction. This is done by analyzing kinetic data in a three-dimensional data space (conversion, temperature, pressure) and attributing the variation of the conversion rate to these independent variables. Thus a reduction from a three-dimensional problem to three one-dimensional problems is achieved. The derivation of a kinetic model can then be performed for each dependency independently, which is easier than deriving a model directly from the data. This work presents the basic approach of the identification and combination of the three dependencies to build a full kinetic model. Also, the interpretation of the model to achieve a physically motivated model is illustrated. Then the method is applied to identify the complex reaction kinetics of the decomposition of CdCO3 based on a set of thermogravimetric measurements. It is shown that it is possible to identify interaction terms between the dependency terms.

Kinetic study for solid-state degradation of mental disorder therapeutic agents

This paper describes the thermal investigations and kinetic analysis regarding the solid-state degradation of three compounds used as mental disorder therapeutic agents (antidepressants), namely amitriptyline, desipramine and imipramine. The study was carried according to ICTAC 2000 recommendations, by using three isoconversional methods, namely Flynn–Wall–Ozawa, Kissinger–Akahira–Sunose and Friedman. The differential method of Friedman indicated multistep degradation, which was later confirmed by the nonparametric kinetic method (NPK). NPK method showed that all three tricyclic antidepressants are degraded by two processes. In terms of apparent activation energies for decomposition, the NPK method indicated 123.4 kJ mol−1 for imipramine, 112.3 kJ mol−1 for desipramine and 82.9 kJ mol−1 for amitriptyline, and the results are in good agreement with the ones suggested by isoconversional methods.

NPK Levels and Application Methods on Productivity of Amorphophallus muelleri Blume in Intercropping System

Underground corm of Amorphophallus muelleri Blume contained glucomannan, a raw material widely used in beverage, food and medicinal industries. In Indonesia, A. muelleri is grown under intercropping system, however, average corm production was considered low. The low productivity could be related to the low input of chemical fertilizers. Therefore, the effects of NPK fertilizers and methods of application on A. muelleri productivity were evaluated in the present study for intercropping system. Two experiments were conducted at Leuwikopo Experimental Farm, Bogor, Indonesia from 2010-2012 under canopy of coffee trees. First experiment was conducted using four levels of N, P, and K applications, i.e., N:P2O5:K2O at the rate 0:0:0, 100:60:80, 125:60:100 and 150:60:120 kg ha-1. In second experiment, N:P2O5:K2O fertilizers at the rate of 100:60:80 were applied by conventional (solid) and liquefied. Results of first experiment showed that application of N, P and K at rate of 100 kg, 60 kg, and 80 kg ha-1 produced fresh corm weight 636.3±91.7 g per plant or increased by 63% higher than control. However, higher rate of NPK application did not increase corm yield, possibly due to the occurrence of leaf discoloration. Higher rates of NPK also delayed harvest time 1 to 2 weeks compared with control and caused wide variation of corm size. Thus, excess application of NPK should be avoided for high productivity of A. muelleri. Second experiment showed that there was no significant different among methods of application on fresh corm weight, i.e., 413 g and 396 g from conventional and liquefied applications, respectively. These experiments conclude that application of NPK is important to enhance A. muelleri production in intercropping system.

NPK Levels and Application Methods on Productivity of Amorphophallus muelleri Blume in Intercropping System

Underground corm of Amorphophallus muelleri Blume contained glucomannan, a raw material widely used in beverage, food and medicinal industries. In Indonesia, A. muelleri is grown under intercropping system, however, average corm production was considered low. The low productivity could be related to the low input of chemical fertilizers. Therefore, the effects of NPK fertilizers and methods of application on A. muelleri productivity were evaluated in the present study for intercropping system. Two experiments were conducted at Leuwikopo Experimental Farm, Bogor, Indonesia from 2010-2012 under canopy of coffee trees. First experiment was conducted using four levels of N, P, and K applications, i.e., N:P2O5:K2O at the rate 0:0:0, 100:60:80, 125:60:100 and 150:60:120 kg ha-1. In second experiment, N:P2O5:K2O fertilizers at the rate of 100:60:80 were applied by conventional (solid) and liquefied. Results of first experiment showed that application of N, P and K at rate of 100 kg, 60 kg, and 80 kg ha-1 produced fresh corm weight 636.3±91.7 g per plant or increased by 63% higher than control. However, higher rate of NPK application did not increase corm yield, possibly due to the occurrence of leaf discoloration. Higher rates of NPK also delayed harvest time 1 to 2 weeks compared with control and caused wide variation of corm size. Thus, excess application of NPK should be avoided for high productivity of A. muelleri. Second experiment showed that there was no significant different among methods of application on fresh corm weight, i.e., 413 g and 396 g from conventional and liquefied applications, respectively. These experiments conclude that application of NPK is important to enhance A. muelleri production in intercropping system.

Thermoanalytical measurements conducted on repaglinide to estimate the kinetic triplet followed by compatibility studies between the antidiabetic agent and various excipients

Repaglinide is an antidiabetic agent that is used in the treatment of the type II diabetes mellitus. In this study, we aimed to determine the thermal behavior of this pharmaceutical agent, as well as the kinetic parameters that characterize the main degradation process of repaglinide. We also targeted a study in which the compatibility of repaglinide with various excipients was evaluated by thermoanalytical and spectrometric techniques. In order to determine the kinetic triplet of the degradation process, the repaglinide was submitted to a controlled degradation process under a temperature program from 40 to 500 °C in air flow of 100 mL min−1 and according to ICTAC 2000 Protocol, samples were heated at five different heating rates: β = 5, 7, 10, 12 and 15 °C min−1, respectively. All data were computed by four isoconversional kinetic methods: FR, FWO, KAS and modified NPK. The compatibility studies implied preparing the binary mixtures of repaglinide and different excipients using a mass ratio of 1:1. For the thermoanalytical evaluation samples of the mixture were analyzed following a temperature program from 40 to 500 °C in air flow of 100 mL min−1 with a heating rate of 10 °C min−1. The spectrometric analysis was performed using the same type of mixtures. The studies show a good compatibility between repaglinide and the five excipients used and also well correlated values of the mean activation energy obtained by FWO, KAS and modified NPK methods.

Comparative thermal stability of two similar-structure hypolipidemic agents

Simvastatin (SIM) and lovastatin (LOV) are two important active pharmaceutical ingredients from statin class, prescribed in the treatment of hypercholesterolemia. Our study presents the results obtained by our research group regarding the decomposition of SIM and LOV in oxidative atmosphere, by employing three isoconversional methods, namely Friedman, Kissinger–Akahira–Sunose and Flynn–Wall–Ozawa. The results obtained by Friedman method suggested a multistep degradation, while the ones obtained by Kissinger–Akahira–Sunose and Flynn–Wall–Ozawa suggested a single-step degradation. In order to validate the results, we used the NPK method, which allowed a concrete separation and nature of processes that contributed to the degradation of both statins. NPK method showed that both SIM and LOV are degraded by contribution of two distinctive chemical processes, and the mean values of activation energies are also reported.

Kinetic analysis of solid-state degradation of pure pravastatin versus pharmaceutical formulation

In this paper, the kinetic behavior of decomposition of a well-known bioactive substance used for treating dyslipidemia and the prevention of cardiovascular disease drug from statin class, namely pravastatin, was described. The kinetic study was performed on the main decomposition process which occurs at nearly 200 °C, for both pure active substance and a generic commercial formulation that contain 40 mg pravastatin per tablet, using Kissinger, Friedman, Kissinger–Akahira–Sunose, Flynn–Wall–Ozawa and NPK methods. The stability of pravastatin as pure active substance and as tablet was compared by means of kinetic data, and the results suggested that in the solid pharmaceutical formulation, PRV has an increased stability compared to pure active substance.

Non-parametric kinetic analysis of thermogravimetric data for the thermal degradation of poly(tetrafluorethylene)

Abstract Thermal degradation of Teflon was investigated by thermoanalytical methods (TG and DTA). In the kinetic analysis of the experimental data, the NPK method proves to be a valuable tool, allowing for some new kinetic aspects of the degradation process to be obtained. Analysis of the computed isothermal and isoconversional vectors provided some insight into the reaction kinetics. Two different initiation pathways were suggested to control the global degradation kinetics, their relative contribution being temperature-dependant

Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data

BackgroundThe thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used.ResultsThe kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporin’s decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one.The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energy’s values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC).ConclusionThe simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps.

Kinetics of thermal decomposition of natrium oxalato-oxo-diperoxo molibdate

Synthesis, characterizations, and thermal behavior of Na2[MoO(O2)2(C2O4)] was studied. The thermally induced events will be observed by comparing the FT-IR spectra of the initial compound and of the char at 300 and 500 °C. The TG data were obtained at different heating rates: β = 2.5, 4, 5, and 10 °C min−1 in air and nitrogen (50 mL min−1), and the TG/DTG data were processed with the following methods: Friedman, Flynn–Wall–Ozawa, and modified NPK method.

Thermal behavior of verapamil in pure and in solid dosage forms

Verapamil is a phenyl-alchil-amine type pharmaceutical largely used as a specific calcium antagonist. Knowledge of drug-excipient compatibility represents an important phase in development of different dosage forms. Hyphenated techniques are versatile for obtaining such necessary information’s. The TG/DTG/DTA curves were obtained in air at different heating rates and in nitrogen. The IR spectra of pure compound and its char at 400 °C (by U-ATR technique) and the IR identification of Evolved Gasses allowed some discussions on the thermally induced events. In the solid dosage forms verapamil was mixed with talc, magnesium stearate, starch, and cellulose, and the corresponding thermoanalytical curves were compared with that one of pure I. No physical or chemical interactions were observed till 250 °C. A kinetic analysis was performed for TG step of verapamil between 250 and 350 °C. The data at four heating rates (7, 10, 12, 15 °C min−1) were processed on a strategy using at last three different kinetic methods. For these, the NPK method seems to be less speculative, allowing an objective determination of the kinetic parameters.

Kinetics of degradation under non-isothermal conditions of a thermooxidative stabilized polyurethane

Abstract A flexible polyurethane (PU) foam prepared from a polyol and an isocyanate prepolymer was stabilized against thermooxidation with two types of compounds: 2,6-di-t-butyl-4-methyl-phenol (non-reactive) and, respectively, 3,5-di-t-butyl-4-hidroxy-benzyl alcohol (reactive). The TG were obtained at different heating rates: β = 5, 7, 10, and 12 °C min−1 and the TG/DTG were processed with the following methods: Freidman, Flynn–Wall–Ozawa, Budrugeac–Segal, and, respectively, Non-Parametric Kinetics. By Freidman and Flynn–Wall–Ozawa methods it was observed a significant (more that 10%) variation of the activation energy, E, versus the conversion degree, this being an indication of a complex process. Therefore, the more sophisticated Budrugeac–Segal and NPK methods were used. The Budrugeac–Segal method presents a very good descriptive ability, so it is useful for simulations of the thermal behavior. The NPK method is the less speculative one and in the majority of cases the obtained values of the activatio...