scholarly journals Thermogravimetric studies of a nasal preparation with an interleukin-1β (IL-1Ra) antagonist

Author(s):  
B. S. Burlaka

Interleukin-1 receptor antagonist (IL-1Ra) is an active pharmaceutical ingredient obtained by the method of gene transformation of Escherichia coli, provides a neuroprotective effect, namely – inhibition of oxidative modification of proteins, normalization of functional activity of mitochondrial energy, mitochondrial energy. Early complex physical-chemical, microbiological, and biopharmaceutical studies have developed a new intranasal formulation, the formulation of which contains: IL-1Ra, sodium carboxymethyl cellulose, D-panthenol, benzalkonium chloride, trilon B, Tween-80, phosphate buffer solution. Given the peculiarities of the technological process, when creating a new gel dosage form, it is necessary to justify the temperature of the carrier base, the introduction of the active substance into the base, as well as to predict the possible chemical interaction of individual components in the dosage form. Therefore, the application of thermogravimetric analysis in pharmaceutical technology is relevant. The aim of the work is to conduct thermogravimetric studies of a new nasal form with an antagonist of interleukin-1β (IL-1Ra). Materials and methods. The objects of thermogravimetric studies were: semi-finished product-solution of the receptor antagonist of interleukin-1 (IL-1Ra). Excipients were: sodium carboxymethylcellulose, tween-80, D-panthenol, trilon B, benzalkonium chloride. To ensure the appropriate pH value used phosphate buffer solution (pH 6.0), according to the recipe to State Pharmacopoeia 2 ed. In addition to the individual components of the finished nasal gel, also prepared nasal gel without IL-1Ra, as well as gel with IL-1Ra. The thermographic analysis was performed on a derivatograph – Shimadzu DTG-60 (Japan) with a platinum-platinum-rhodium thermocouple when heating the samples in aluminum crucibles (from 15 °C to 250 °C). Al2O3 was used as a reference substance. The heating rate was 10 °C per minute. The weight of the test samples ranged from 19.22 mg to 52.91 mg. The derivatograph graphically recorded the obtained data in the form of curves T, DTA, TGA. The T curve on the derivatogram shows the change in temperature, and the TGA curve shows the change in mass of the sample during the study period. The DTA curve reflects the differentiation of thermal effects, contains information about endothermic and exothermic maxima, can be used for qualitative evaluation of the derivatogram. Results. The study consisted of two stages. At the first stage, we studied the derivatograms of experimental samples – individual ingredients of the finished nasal gel - active and excipients, namely: IL-1Ra, sodium carboxymethylcellulose, tween-80, D-panthenol, trilon B, benzalkonium chloride, phosphate buffer solution 6.0. In the second stage, samples of nasal gels were prepared: nasal gel with the required amount of excipients, in addition to the active substance – IL-1Ra, as well as a nasal gel containing IL-1Ra and the required amount of excipients. As a result, we obtained some parameters of thermogravimetric analysis in the form of a graphical image – derivatograms, which were then analyzed. Conclusions. Thermogravimetric studies of individual components of nasal gel with IL-1Ra, as well as nasal gels with active substance and without active substance, were found that the manufacturing process of gel with IL-1Ra should be carried out taking into account thermolabile compounds. First, you need to prepare the base without preservative and IL-1Ra. Then at a temperature not exceeding 40 °C dissolve the preservative, and then when cooled to 20 °C add IL-1Ra. It was found that the developed dosage form of the gel with IL-1Ra is a mixture of active and excipients, the ingredients of which do not interact with each other and can be combined in one dosage form.

2021 ◽  
pp. 43-49
Author(s):  
B. S. Burlaka

In the development of new effective and safe drugs an important place is occupied by the issue of ensuring the stability of the dosage form. In this case, a significant contribution to this problem is made directly by the nature of the active pharmaceutical ingredient. Based on our experimental studies, the composition of the base-carrier of the nasal drug with the receptor antagonist intereleukin-1 (IL-1ra) was determined, and the need to add a preservative was identified. However, focusing on the peptide nature of the biologically active component of IL-1ra, it is necessary to take into account the possible lack of stability during storage of the drug with changes in pH. The aim of the work is to optimize the composition of a nasal drug with an interleukin antagonist (IL-1ra) to increase its storage stability. As the active pharmaceutical ingredient used a semi-finished solution of the receptor antagonist of interleukin-1 (IL-1ra). Excipients were: sodium carboxymethylcellulose, tween-80, D-panthenol, trilon B, benzalkonium chloride. To ensure the appropriate pH value used phosphate buffer solutions, which were prepared according to State Pharmacopoeia. The study of some indicators of pharmaceutical availability (kinetic indicators) was performed by studying the release of the active ingredient from the drug composition by equilibrium dialysis in purified water. Equilibrium dialysis was performed through Cuprofan cellophane film at 37 ± 0.5 °C in Franz Diffusion Cell System. The content of IL-1ra in the dialysate was determined spectrophotometrically, at certain intervals. As a result of pharmaco-technological studies to optimize the composition of the nasal agent with IL-1ra, it was found that the developed nasal agent with IL-1ra requires the addition of stabilizers to the composition of the formulation. It was found that the use as stabilizers: phosphate buffer solution 6.0 and trilon B, provides proper release of the active substance from the dosage form and corrects the stability of the hydrogen index over time. The obtained results of pharmaceutical availability indicators indicate that the release of IL-1ra from the nasal form is subject to the first order equation.


1975 ◽  
Vol 21 (4) ◽  
pp. 521-526 ◽  
Author(s):  
N. Lisker ◽  
J. Katan ◽  
I. Chet ◽  
Y. Henis

Propagules of Rhizoctonia solani grown in modified Czapek's medium containing sodium polypectate or carboxymethyl cellulose as a sole carbon source produced both extracellular and cell-bound polygalacturonase (PG), and cellulase (Cx), respectively. The cell-bound enzymes can be released to various extents by shaking the germinating propagules in solutions of NaCl, KCl, phosphate buffer, Na2EDTA (ethylenediaminetetraacetate), detergents such as Triton X-100 (octyl phenoxypolyethoxyethanol), Tween 80 (polyoxyethylene sorbitan monooleate), Celmusol, and distilled water. Sodium dodecyl sulfate (SDS) inactivated both PG and Cx but did not affect Cx activity in phosphate buffer solution. PG was more easily released by salts from the mycelium of R. solani than Cx. The release of both enzymes was a passive process and was not due to an osmotic effect. The amount of the cell-bound fraction was correlated with the total amount of the extracellular fraction rather than with the mycelial growth. At least one-third of the cell-bound fractions of both enzymes was found to be associated with the cell wall fraction of the mycelium.


2010 ◽  
Vol 7 (1) ◽  
pp. 320-324 ◽  
Author(s):  
L. Latheeshjlal ◽  
P. Parthiban ◽  
V. Alagarsamy ◽  
M. Sunil ◽  
J. Vaidhya Mahul ◽  
...  

Simple, rapid and accurate, spectrophotometric method for the determination of losartan potassium by using bromothymol blue as a chromogen and phosphate buffer solution (pH 3-4) as a diluting agent was developed. The developed colour shows maximum absorbance at 620 nm and it was observed that the absorbance of different dilution from the plots the calibration curve between the concentrations in x-axis, absorbance at y-axis. The recovery studies were also carried out to ensure the reproducibility and repeatability. This recovery studies shows between 96.82-100.08% for the different formulation. Hence, it was concluded that the developed simple, precise and accurate method can be effectively used for the routine analysis of losartan potassium


2006 ◽  
Vol 510-511 ◽  
pp. 798-801
Author(s):  
Hyung Suk So ◽  
Hyun Chul Shin ◽  
Beom Suk Kim ◽  
Yeong Seok Yoo

The purpose of this study is to develop a new system to control effective discharge of active substances such as agricultural chemicals. To synthesize a naturally dissolvable polymer; ε-caprolactone and diglycolide were copolymerized with ethylene glycol as an initiator to produce macrodiol. As macrodiol has hydroxyl groups in both ends, they are modified with methacryloyl chloride for photochemical networking. After standard macromonomer produced by this procedure was physically mixed with methylene blue, it was networked with ultra-violet rays to be filmed. This film is naturally dissolvable and hydrolytic. As a result of hydrolytic test with a crosslinked structure of 10 % methylene blue, it decreased by 9 % for seven weeks in 37 °C phosphate buffer solution (pH = 7). Thus, we verified that active substance can be discharged from a crosslinked structure for a long time at a constant rate under room temperature.


2011 ◽  
Vol 284-286 ◽  
pp. 1764-1769 ◽  
Author(s):  
Vitalijs Lakevics ◽  
Janis Locs ◽  
Dagnija Loca ◽  
Valentina Stepanova ◽  
Liga Berzina-Cimdina ◽  
...  

Sorption experiments of bovine serum albumin (BSA) on hydroxyapatite (HAp) ceramic granules, prepared at three temperatures 900°C, 1000°C and 1150°C were performed at room temperature 18,6 °C and phosphate buffer, pH 5,83; 6.38 and 7,39. Thermal treatment contributed to the decrease of bovine serum albumin immobilization indicating that sorption process depended on HAp ceramics specific surface area and pH values of phosphate buffer solution. However, it was confirmed that granule size was also an important parameter for bovine serum albumin adsorption. As a result of these experiments, the most appropriate adsorption conditions and phosphate buffer pH values influence on to BSA sorption were analyzed.


2000 ◽  
Vol 63 (6) ◽  
pp. 703-708 ◽  
Author(s):  
MARCY A. WISNIEWSKY ◽  
BONITA A. GLATZ ◽  
MARK L. GLEASON ◽  
CHERYLL A. REITMEIER

The objectives of this study were to determine if washing of whole apples with solutions of three different sanitizers (peroxyacetic acid, chlorine dioxide, or a chlorine-phosphate buffer solution) could reduce a contaminating nonpathogenic Escherichia coli O157:H7 population by 5 logs and at what sanitizer concentration and wash time such a reduction could be achieved. Sanitizers were tested at 1, 2, 4, 8, and 16 times the manufacturer's recommended concentration at wash times of 5, 10, and 15 min. Whole, sound Braeburn apples were inoculated with approximately 1 × 108 or 7 × 106 CFU per apple, stored for 24 h, then washed with sterile water (control) or with sanitizers for the prescribed time. Recovered bacteria were enumerated on trypticase soy agar. Washing with water alone reduced the recoverable population by almost 2 logs from the starting population; this can be attributed to physical removal of organisms from the apple surface. No sanitizer, when used at the recommended concentration, reduced the recovered E. coli population by 5 logs under the test conditions. The most effective sanitizer, peroxyacetic acid, achieved a 5-log reduction when used at 2.1 to 14 times its recommended concentration, depending on the length of the wash time. The chlorine-phosphate buffer solution reduced the population by 5 logs when used at 3 to 15 times its recommended concentration, depending on wash time. At no concentration or wash time tested did chlorine dioxide achieve the 5-log reduction.


2018 ◽  
Vol 10 (11) ◽  
pp. 1362-1371 ◽  
Author(s):  
Mallappa Mahanthappa ◽  
Nagaraju Kottam ◽  
Shivaraj Yellappa

The simultaneous electroanalysis of acetaminophen (AC), guanine (G) and adenine (A) was successfully achieved on the zinc sulphide nanoparticles-modified carbon paste electrode (ZnS NPs/CPE) in phosphate buffer solution (PBS).


Author(s):  
Amitava Dutta ◽  
Apurba Kumar Santra ◽  
Ranjan Ganguly

Abstract We present a detailed numerical analysis of electrophoresis induced concentration of a bio-analyte facilitated by temperature gradient focusing in a phosphate buffer solution via Joule heating inside a converging-diverging microchannel. The purpose is to study the effects of frequency of AC field and channel width variation on the concentration of target analyte. We tune the buffer viscosity, conductivity and electrophoretic mobility of the analyte such that the electrophoretic velocity of the analyte locally balances the electroosmotic flow of the buffer, resulting in a local build-up of the analyte concentration in a target region. An AC field is superimposed on the applied DC field within the microchannel in such a way that the back pressure effect is minimized, resulting in minimum dispersion and high concentration of the target analyte. Axial transport of fluorescein-Na in the phosphate buffer solution is controlled by inducing temperature gradient through Joule heating. The technique leverages the fact that the buffer's ionic strength and viscosity depends on temperature, which in turn guides the analyte transport. A numerical model is proposed and a finite element-based solution of the coupled electric field, mass, momentum, energy and species equations are carried out. Simulation predict peak of 670-fold concentration of fluorescein-Na is achieved. The peak concentration is found to increase sharply as the channel throat width, while the axial spread of concentrated analyte increases at lower frequency of AC field. The results of the work may improve the design of micro concentrator.


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