Kinetics study of hydrochlorothiazide lactose liquid state interaction using conventional isothermal arrhenius method under basic and neutral conditions

The Maillard reaction of hydrochlorothiazide (HCTZ) and lactose has been previously demonstrated in pharmaceutical formulations. In this study, the activation energy of - hydrohlorothiazide and lactose interaction in the liquid state was ascertained under basic and neutral conditions. Conventional isothermal High Performance Liquid Chromatography (HPLC) technique was employed to ascertain the kinetic parameters using Arrhenius method. Results: The activation energy obtained was 82.43 and 100.28 kJ/mol under basic and neutral conditions, respectively. Consequently, it can be inferred that Maillard reaction is significantly affected by pH, which can be used as a control factor whenever the reaction potentially occurs

Kinetic analysis of drug release from nanoparticles

PURPOSE. Comparative drug release kinetics from nanoparticles was carried out using conventional and our novel models with the aim of finding a general model applicable to multi mechanistic release. Theoretical justification for the two best general models was also provided for the first time. METHODS. Ten conventional models and three models developed in our laboratory were applied to release data of 32 drugs from 106 nanoparticle formulations collected from literature. The accuracy of the models was assessed employing mean percent error (E) of each data set, overall mean percent error (OE) and number of Es less than 10 percent. RESULTS. Among the models the novel reciprocal powered time (RPT), Weibull (W) and log-probability (LP) ones produced OE values of 6.47, 6.39 and 6.77, respectively. The OEs of other models were higher than 10%. Also the number of errors less than 10% for the models was 84.9, 80.2 and 78.3 percents of total number of data sets. CONCLUSIONS. Considering the accuracy criteria the reciprocal powered time model could be suggested as a general model for analysis of multi mechanistic drug release from nanoparticles. Also W and LP models were the closest to the suggested model RPT

Filgrastim (G-CSF) loaded liposomes: mathematical modeling and optimization of encapsulation efficiency and particle size

Introduction: Optimization of filgrastim (G-CSF) (granulocyte colony stimulating factor) liposomes formulation prepared by the method of film hydration was the aim of this research. Methods: To study the independent variables effects in the development of filgrastim (G-CSF) liposomes, method of factorial design was applied. The molar ratio of dipalmitoyl phophatidylcholine (DPPC) per cholesterol (Chol.) and hydration time were chosen as two independent factors. The dependent variables were encapsulation efficiency percent (EE %) and particle size (PS). Ultrafiltration method was applied for separation of un-encapsulated protein. RP-HPLC method was employed for analysis of G-CSF. Results: Application of response surface methodology (RSM) in formulation of filgrastim liposomes and the obtained results for responses including particle size and EE % showed that the main effective independent variable was DPPC/Chol molar ratio. Different impacts of influencing parameters including interaction and individual effects were checked employing a mathematical method for obtaining desired liposomes. Optimum liposomal formulations were established using this method for enhancing their characteristics. Average percent errors (APEs) were 3.86% and 3.27% for predicting EE % and PS, respectively which reflect high model ability in this regard. Conclusion: It is concluded that observed and predicted values regarding PS and EE % were consistent and this model is efficient enough in prediction of the mentioned characteristics while preparing filgrastim (G-CSF) liposomes

Physicochemical analysis and nonisothermal kinetic study of sertraline–lactose binary mixtures

In the present study the physicochemical stability of sertraline with lactose was evaluated in drug-excipient binary mixtures. Different physicochemical methods such as differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy, and mass spectrometry were applied to confirm the incompatibility. The final aim of this study was to evaluate the kinetic parameters using a fast and sensitive DSC method. Solid-state kinetic parameters were derived from nonisothermally stressed physical mixtures using different thermal models such as Friedman, Flynn–Wall–Ozawa, and Kissinger–Akahira–Sunose. Overall, the instability of sertraline with lactose was successfully evaluated. Further confirmation was made by tracking the Maillard reaction product of sertraline and lactose by mass spectrometry. DSC scans provided important information about the stability of sertraline in solid-state condition and also revealed the related thermokinetic parameters in order to understand the nature of the chemical instability

Kinetics study of hydrochlorothiazide lactose liquid state interaction using conventional isothermal arrhenius method under basic and neutral conditions

ABSTRACT The Maillard reaction of hydrochlorothiazide (HCTZ) and lactose has been previously demonstrated in pharmaceutical formulations. In this study, the activation energy of - hydrohlorothiazide and lactose interaction in the liquid state was ascertained under basic and neutral conditions. Conventional isothermal High Performance Liquid Chromatography (HPLC) technique was employed to ascertain the kinetic parameters using Arrhenius method. Results: The activation energy obtained was 82.43 and 100.28 kJ/mol under basic and neutral conditions, respectively. Consequently, it can be inferred that Maillard reaction is significantly affected by pH, which can be used as a control factor whenever the reaction potentially occurs

Determination of aflatoxins in nuts of Tabriz confectionaries by ELISA and HPLC methods

Purpose: Aflatoxins (AFs) are a group of mycotoxins and secondary metabolites of various species of Aspergillus. There are various forms of aflatoxins including B1, B2, G1, G2, M1 and M2 types. Aflatoxins cause important health problems and have high potential effect on liver cancer. Therefore, numerous investigations have been conducted during last three decades. The aim of this work is to determine the contamination levels of nuts used by the confectionaries in Tabriz. Methods: A total of 142 samples including 35 almond , 26 walnut, 4 seeds of apricot, 6 sunflower seeds kernel, 6 sesame seed, 6 peanuts , 32 pistachio,13 hazelnuts and 14 cashews samples were collected from Tabriz confectionaries. The ELISA method was employed for the screening of total aflatoxins. Results: In 13 cases (28.1% of pistachios, 5.1% of walnuts and 7.1% of cashews) contamination rate of higher than 15 ppb were observed. The HPLC method was applied for the confirmation of ELISA results. Aflatoxin B1 was the highest detected AFs. Conclusion: The overall results of the tested samples indicated that the rate of contamination of pistachios is higher than the other tested samples

Cogrinding as an approach to enhance dissolution rate of a poorly water-soluble drug (gliclazide)

Gliclazide is practically insoluble in water. In order to improve the drug dissolution rate, cogrinding method was used as an approach to prepare gliclazide coground/solid dispersions (SDs) in the carriers such as povidone (PVP-K30), crospovidone and microcrystalline cellulose (Avicel PH 101) with different drug to carrier ratios. The dissolution rate of gliclazide from the SDs was measured at two physiological pH values of 1.2 and 7.2 simulating gastric and intestinal fluids using USP dissolution apparatus II. The concentration of the dissolved drug in the medium was determined by direct or first-derivative UV spectroscopy. The dissolution rates of the formulations were dependent on the nature and ratio of drug to carriers in SDs and the corresponding physical mixtures as well as the pH of the medium. At a higher pH the drug has a faster dissolution than at a lower pH. The fastest dissolution rates were observed from coground formulations with the drug to carrier ratio of 1:5. The amount of drug dissolved in 15 min from these SDs was varied from 96% in the case of Avicel SD to 100% for SD of PVP. Whereas the amount of drug released in the same time from unground drug powder (UD), ground drug powder (GD) and all physical mixtures was between 60 and 80%. These results indicate that the dissolution rate is highly enhanced from the SDs. DSC as well as X-ray diffraction showed reduced drug crystallinity in SDs. Scanning electron microscopy and particle size analysis revealed significant decreased particle size of the drug in SDs. FT-IR spectroscopy demonstrated no detectable interactions between the drug and carriers. In addition to latter evidence, increased wettability and hydrophilicity of drug particles and deaggregation brought about by the carriers are the reasons for enhanced drug dissolution from the SDs. One of the possible advantages of formulating an insoluble drug such as gliclazide is that if it is used in preparation of capsules or tablets of the drug, its dose might be reduced which is economically beneficial. © 2009 Elsevier B.V. All rights reserved

In vitro and in vivo evaluation of insulin microspheres containing protease inhibitor

The aim of this study was to investigate the applicability of microspheres containing protease inhibitor for oral delivery of insulin (CAS 9004-10-8). Microspheres of insulin were prepared by water-in-oil-in-oil (w/o 1/o2) double emulsion solvent evaporation method. Formulations with different drug/polymer ratios were prepared and characterized by drug loading, loading efficiency, yield, particle size, scanning electron microscopy (SEM), Fourier Transform Infrared spectroscopy (FTIR). The in vitro release studies were performed in pH 1.2 and 7.4. In vivo studies on rats were conducted in order to investigate the bioavailability and performance of oral microspheres. The best polymer to drug ratio in microspheres was 15.6:1 (F 2 formulation). The loading efficiency was 77.36%, production yield was 54.55 % and mean particle size was 222.4 μm. SEM studies showed that the microspheres were spherical and porous in nature. Data obtained from in vitro release were fitted to various kinetic models and high correlation was obtained in the first order model. The results of enzymatic degradation indicated that insulin could be protected from trypsinic degradation in the microspheres. Our results indicate that the microspheres containing aprotinin (CAS 9087-70-1) have the advantage of high loading efficiency, pH responsive and prolonged release carrying insulin to the optimumsite of absorption as well as the enhanced insulin absorption and biological response. © ECV • Editio Cantor Verlag