Model and Kinetic Parameters Identification for Therapeutical Product Obtained According to the GMP Guidelines

2008 ◽  
Vol 59 (7) ◽  
Author(s):  
Camelia Ungureanu ◽  
Mihai Caramihai ◽  
Ana Aurelia Chirvase ◽  
Ovidiu Muntean ◽  
Iosif Nagy ◽  
...  

The technological solutions were elaborated to achieve the design of the production flow with respect of the Good Manufacturing Practice (GMP) guidelines. To be in line with the GMP rules a fed-batch operation mode is be designed based on the batch modelling results. As the production rate of the microbial immunomodulator is associated with the biomass growth rate, it was required to study the bacterium growth kinetics in batch process. After the selection of the kinetic model based on several batches experimental data by using the analysis criteria - modelling error and estimation rule convergence, the limiting substrate concentration to be maintained during fed-batch cells exponential growth was determined as 115 - 125 mg/L. The batch bioprocess was performed in a Bioengineering AG bioreactor with a software based control of the main variables.

2015 ◽  
Author(s):  
Alexandre Soares dos Santos ◽  
Nei Pereira Jr ◽  
Denise M G Freire

Rhamnolipids are biosurfactants with potential for diversified industrial and environmental uses. The present study evaluated three strategies to increase the production of rhamnolipid-type biosurfactants produced by Pseudomonas aeruginosa strain PA1. The influence of pH, the addition of endogenous autoinducers and the use of a fed batch process were examined. The culture medium adjusted to pH 7.0 was the most productive. Furthermore, the pH of the culture medium had a measurable effect on the ratio of mono- and dirhamnolipids synthesized. At pH values below 7.3, the proportion of monorhamnolipids decreased from 45 to 24%. Additionally, recycling 20% of the spent culture medium where P. aeruginosa was grown up to the later stationary phase was responsible for a 100% increase in rhamnolipid volumetric productivity in the new culture medium. Finally, the use of fed batch operation under conditions of limited nitrogen resulted in a 3.8-fold increase in the amount of rhamnolipids produced (1.29 g L-1 to 4.90 g L-1, as rhamnose). These results offer promising paths to optimize processes for the production of rhamnolipids.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2078 ◽  
Author(s):  
Alexandre Soares dos Santos ◽  
Nei Pereira Jr ◽  
Denise M.G. Freire

Rhamnolipids are biosurfactants with potential for diversified industrial and environmental uses. The present study evaluated three strategies for increasing the production of rhamnolipid-type biosurfactants produced byPseudomonas aeruginosastrain PA1. The influence of pH, the addition ofP. aeruginosaspent culture medium and the use of a fed-batch process were examined. The culture medium adjusted to pH 7.0 was the most productive. Furthermore, the pH of the culture medium had a measurable effect on the ratio of synthesized mono- and dirhamnolipids. At pH values below 7.3, the proportion of monorhamnolipids decreased from 45 to 24%. The recycling of 20% of the spent culture medium in whereP. aeruginosawas grown up to the later stationary phase was responsible for a 100% increase in rhamnolipid volumetric productivity in the new culture medium. Finally, the use of fed-batch operation under conditions of limited nitrogen resulted in a 3.8-fold increase in the amount of rhamnolipids produced (2.9 g L−1–10.9 g L−1). These results offer promising pathways for the optimization of processes for the production of rhamnolipids.


Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 365
Author(s):  
Ana C. D. Pfluck ◽  
Dragana P.C. de Barros ◽  
Luis P. Fonseca

An innovative enzymatic polycondensation of dicarboxylic acids and dialcohols in aqueous polymerization media using free and immobilized lipases was developed. Various parameters (type of lipases, temperature, pH, stirring type and rate, and monomer carbon chain length) of the polycondensation in an oil-in-water (o/w) miniemulsion (>80% in water) were evaluated. The best results for polycondensation were achieved with an equimolar monomer concentration (0.5 M) of octanedioic acid and 1,8-octanediol in the miniemulsion and water, both at initial pH 5.0 with immobilized Pseudozyma antarctica lipase B (PBLI). The synthesized poly(octamethylene suberate) (POS) in the miniemulsion is characterized by a molecular weight of 7800 g mol−1 and a conversion of 98% at 45 °C after 48 h of polycondensation in batch operation mode. A comparative study of polycondensation using different operation modes (batch and fed-batch), stirring type, and biocatalyst reutilization in the miniemulsion, water, and an organic solvent (cyclohexane:tetrahydrofuran 5:1 v/v) was performed. Regarding the polymer molecular weight and conversion (%), batch operation mode was more appropriate for the synthesis of POS in the miniemulsion and water, and fed-batch operation mode showed better results for polycondensation in the organic solvent. The miniemulsion and water used as polymerization media showed promising potential for enzymatic polycondensation since they presented no enzyme inhibition for high monomer concentrations and excellent POS synthesis reproducibility. The PBLI biocatalyst presented high reutilization capability over seven cycles (conversion > 90%) and high stability equivalent to 72 h at 60 °C on polycondensation in the miniemulsion and water. The benefits of polycondensation in aqueous media using an o/w miniemulsion or water are the origin of the new concept strategy of the green process with a green product that constitutes the core of the new greener polymer-5B technology.


2015 ◽  
Author(s):  
Alexandre Soares dos Santos ◽  
Nei Pereira Jr ◽  
Denise M G Freire

Rhamnolipids are biosurfactants with potential for diversified industrial and environmental uses. The present study evaluated three strategies to increase the production of rhamnolipid-type biosurfactants produced by Pseudomonas aeruginosa strain PA1. The influence of pH, the addition of endogenous autoinducers and the use of a fed batch process were examined. The culture medium adjusted to pH 7.0 was the most productive. Furthermore, the pH of the culture medium had a measurable effect on the ratio of mono- and dirhamnolipids synthesized. At pH values below 7.3, the proportion of monorhamnolipids decreased from 45 to 24%. Additionally, recycling 20% of the spent culture medium where P. aeruginosa was grown up to the later stationary phase was responsible for a 100% increase in rhamnolipid volumetric productivity in the new culture medium. Finally, the use of fed batch operation under conditions of limited nitrogen resulted in a 3.8-fold increase in the amount of rhamnolipids produced (1.29 g L-1 to 4.90 g L-1, as rhamnose). These results offer promising paths to optimize processes for the production of rhamnolipids.


2020 ◽  
Vol 16 (6) ◽  
pp. 928-933
Author(s):  
Jujjavarapu S. Eswari

Objective: Biosurfactants are the surface active agents which are used for the reduction of surface and interfacial tensions of liquids. Rhamnolipids are the surfactants produced by Pseudomonas aeruginosa. It requires minimum nutrition for its growth as it can also grow in distilled water. The rhamnolipids produced by Pseudomonas aeruginosa are extra-cellular glycolipids consisting of L-rhamnose and 3-hydroxyalkanoic acid. Methods: The fed-batch method for the rhamnolipid production is considered in this study to know the influence of the carbon, nitrogen, phosphorous substrates as growth-limiting nutrients. Pulse feeding is employed for limiting nutrient addition at particular time interval to obtain maximum rhamnolipid formation from Pseudomonas aeruginosa compared with the batch process. Results: Out of 3 fed batch strategies constant glucose fed batch strategy shows best and gave maximum rhamnolipid concentration of 0.134 g/l.


Fermentation ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. 62
Author(s):  
Konstantins Dubencovs ◽  
Janis Liepins ◽  
Arturs Suleiko ◽  
Anastasija Suleiko ◽  
Reinis Vangravs ◽  
...  

The Kluyveromyces marxianus yeast recently has gained considerable attention due to its applicability in high-value-added product manufacturing. In order to intensify the biosynthesis rate of a target product, reaching high biomass concentrations in the reaction medium is mandatory. Fed-batch processes are an attractive and efficient way how to achieve high cell densities. However, depending on the physiology of the particular microbial strain, an optimal media composition should be used to avoid by-product synthesis and, subsequently, a decrease in overall process effi-ciency. Thus, the aim of the present study was to optimise the synthetic growth medium and feeding solution compositions (in terms of carbon, nitrogen, phosphorous, magnesium, and calcium concentrations) for high cell density K. marxianus fed‑batch cultivations. Additionally, the biomass yields from the vitamin mixture and other macro/microelements were identified. A model predictive control algorithm was successfully applied for a fed-batch cultivation control. Biomass growth and substrate consumption kinetics were compared with the mathematical model predictions. Finally, 2‑phenylethanol biosynthesis was induced and its productivity was estimated. The determined optimal macronutrient ratio for K. marxianus biomass growth was identified as C:N:P = 1:0.07:0.011. The maximal attained yeast biomass concentration was close to 70 g·L-1 and the 2-PE biosynthesis rate was 0.372 g·L−1·h−1, with a yield of 74% from 2-phenylalanine.


2019 ◽  
Vol 15 (2) ◽  
pp. 1900088 ◽  
Author(s):  
Tobias Habicher ◽  
Edward K. A. Rauls ◽  
Franziska Egidi ◽  
Timm Keil ◽  
Tobias Klein ◽  
...  

2001 ◽  
Vol 24 (2) ◽  
pp. 65-71 ◽  
Author(s):  
Rouf S. ◽  
Douglas P. ◽  
Moo-Young M. ◽  
Scharer J.

2017 ◽  
Vol 12 (7) ◽  
pp. 1600633 ◽  
Author(s):  
Matthias Brunner ◽  
Philipp Braun ◽  
Philipp Doppler ◽  
Christoph Posch ◽  
Dirk Behrens ◽  
...  

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