scholarly journals Evolutionary Algorithms in Modeling Aerodynamic Properties of Spray-Dried Microparticulate Systems

2020 ◽  
Vol 10 (20) ◽  
pp. 7109
Author(s):  
Adam Pacławski ◽  
Jakub Szlęk ◽  
Renata Jachowicz ◽  
Stefano Giovagnoli ◽  
Barbara Wiśniowska ◽  
...  
Keyword(s):  
Evolutionary Algorithms ◽  
Spray Drying ◽  
Particle Interaction ◽  
Predictive Ability ◽  
Single Step ◽  
Coefficient Of Determination ◽  
Drying Process ◽  
Formulation Development ◽  
Aerodynamic Properties

Spray drying is a single step process in which solutions or dispersions are converted into dry particles. It is widely used in pharmaceutical technology to produce inhalable particles. Dry particle behavior during inhalation, described as the emitted dose (ED) and fine particle fraction (FPF), is determined in vitro by standardized procedures. A large number of factors influencing the spray drying process and particle interaction makes it difficult to predict the final product properties in advance. This work presents the development of predictive models based on experimental data obtained by aerodynamic assessment of respirable dry powders. Developed models were tested according to the 10-fold cross-validation procedure and yielded good predictive ability. Both models were characterized by normalized root-mean-square error (NRMSE) below 8.50% and coefficient of determination (R2) above 0.90. Moreover, models were analyzed to establish a relationship between spray drying process parameters and the final product quality measures. Presented work describes the strategy of implementing the evolutionary algorithms in empirical model’s development. Obtained models can be applied as an expert system during pharmaceutical formulation development. The models have the potential for product optimization and a knowledge extraction to improve final quality of the drug.

scholarly journals Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals

2021 ◽  
Author(s):  
Durairaj Thiyagarajan ◽  
Benedikt Huck ◽  
Birgit Nothdurft ◽  
Marcus Koch ◽  
David Rudolph ◽  
...  
Keyword(s):  
Spray Drying ◽  
Focused Ion Beam ◽  
Colloidal Stability ◽  
Ion Beam ◽  
Pulmonary Delivery ◽  
Active Pharmaceutical Ingredient ◽  
Dry Powder ◽  
Aerodynamic Properties ◽  
Model Cell

AbstractPulmonary delivery of nanocarriers for novel antimycobacterial compounds is challenging because the aerodynamic properties of nanomaterials are sub-optimal for such purposes. Here, we report the development of dry powder formulations for nanocarriers containing benzothiazinone 043 (BTZ) or levofloxacin (LVX), respectively. The intricacy is to generate dry powder aerosols with adequate aerodynamic properties while maintaining both nanostructural integrity and compound activity until reaching the deeper lung compartments. Microparticles (MPs) were prepared using vibrating mesh spray drying with lactose and leucine as approved excipients for oral inhalation drug products. MP morphologies and sizes were measured using various biophysical techniques including determination of geometric and aerodynamic mean sizes, X-ray diffraction, and confocal and focused ion beam scanning electron microscopy. Differences in the nanocarriers’ characteristics influenced the MPs’ sizes and shapes, their aerodynamic properties, and, hence, also the fraction available for lung deposition. Spay-dried powders of a BTZ nanosuspension, BTZ-loaded silica nanoparticles (NPs), and LVX-loaded liposomes showed promising respirable fractions, in contrast to zirconyl hydrogen phosphate nanocontainers. While the colloidal stability of silica NPs was improved after spray drying, MPs encapsulating either BTZ nanosuspensions or LVX-loaded liposomes showed the highest respirable fractions and active pharmaceutical ingredient loads. Importantly, for the BTZ nanosuspension, biocompatibility and in vitro uptake by a macrophage model cell line were improved even further after spray drying. Graphical abstract

Formulation and Evaluation of Immediate Release Bilayer Tablets of Telmisartan and Hydrochlorothiazide

2011 ◽  
Vol 4 (3) ◽  
pp. 1477-1483
Author(s):  
Natarajan R ◽  
N Patel ◽  
Rajendran N N ◽  
M Rangapriya
Keyword(s):  
Antihypertensive Drugs ◽  
In Vitro Release ◽  
Immediate Release ◽  
Wet Granulation ◽  
Physical Parameters ◽  
Dissolution Profile ◽  
Formulation Development ◽  
Sodium Starch Glycolate ◽  
Bilayer Tablets

The main goal of this study was to develop a stable formulation of antihypertensive drugs telmisartan and hydrochlorothiazide as an immediate-release bilayer tablet and to evaluate the dissolution profile in comparison with a reference product. The formulation development work was initiated with wet granulation. Telmisartan was converted to its sodium salt by dissolving in aqueous solution of sodium hydroxide to improve solubility and drug release. Lactose monohydrate and microcrystalline cellulose were used as diluents. Starch paste is prepared in purified water and was used as the binder. Sodium starch glycolate is added as a disintegrating agent. Magnesium stearate was used as the lubricant. The prepared granules were compressed into a double-layer compression machine. The tablets thus formulated with higher proportion of sodium starch glycolate showed satisfactory physical parameters, and it was found to be stable and in vitro release studies are showed that formulation (F-T5H5) was 101.11% and 99.89% respectively. The formulation T5H5 is further selected and compared with the release profile of the innovator product, and was found to be similar (f2 factor) to that of the marketed product. The results suggest the feasibility of developing bilayer tablets consisting of telmisartan and hydrochlorothiazide for the convenience of patients with hypertension.  

Moxifloxacin Hydrochloride-Loaded Eudragit® RL 100 and Kollidon® SR Based Nanoparticles: Formulation, In vitro Characterization and Cytotoxicity.

2020 ◽  
Vol 23 ◽  
Author(s):  
Gülsel Yurtdaş Kırımlıoğlu ◽  
Sinan Özer ◽  
Gülay Büyükköroğlu ◽  
Yasemin Yazan
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Spray Drying ◽  
Prolonged Release ◽  
Ocular Delivery ◽  
Corneal Permeability ◽  
Release Pattern ◽  
In Vitro Characterization ◽  
Ocular Bioavailability

Background: Considering the low ocular bioavailability of conventional formulations used for ocular bacterial infection treatment, there’s a need for designing efficient novel drug delivery systems that may enhance of precorneal retention time and corneal permeability. Aim and Objective: The current research focuses on developing nanosized and non-toxic Eudragit® RL 100 and Kollidon® SR nanoparticles loaded with moxifloxacin hydrochloride (MOX) for its prolonged release to be promising for effective ocular delivery. Methods: In this study, MOX was incorporation was carried out by spray drying method aiming ocular delivery. In vitro characteristics were evaluated in detail with different methods. Results: MOX was successfully incorporated into Eudragit® RL 100 and Kollidon® SR polymeric nanoparticles by spray-drying process. Particle size, zeta potential, entrapment efficiency, particle morphology, thermal, FTIR, XRD and NMR analyses and MOX quantification using HPLC method were carried out to evaluate the nanoparticles prepared. MOX loaded nanoparticles demonstrated nanosized and spherical shape while in vitro release studies demonstrated modified release pattern which followed Korsmeyer-Peppas kinetic model. Following successful incorporation of MOX into the nanoparticles, the formulation (MOX: Eudragit® RL 100, 1:5) (ERL-MOX 2) was selected for further studies by the reason of its better characteristics like cationic zeta potential, smaller particle size, narrow size distribution and more uniform prolonged release pattern. Moreover, ERL-MOX 2 formulation remained stable for 3 months and demonstrated higher cell viability values for MOX. Conclusion: In vitro characterization analyses showed that non-toxic, nano-sized and cationic ERLMOX 2 formulation has the potential of enhancing ocular bioavailability.

Hybrid Design of Isonicotinic Acid Hydrazide Derivatives: Machine Learning Studies, Synthesis and Biological Evaluation of their Antituberculosis Activity

2020 ◽  
Vol 17 (3) ◽  
pp. 365-375
Author(s):  
Vasyl Kovalishyn ◽  
Diana Hodyna ◽  
Vitaliy O. Sinenko ◽  
Volodymyr Blagodatny ◽  
Ivan Semenyuta ◽  
...  
Keyword(s):  
Machine Learning ◽  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Predictive Ability ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Starting Point ◽  
Binary Classifiers ◽  
Synthesis And Biological Evaluation

Background: Tuberculosis (TB) is an infection disease caused by Mycobacterium tuberculosis (Mtb) bacteria. One of the main causes of mortality from TB is the problem of Mtb resistance to known drugs. Objective: The goal of this work is to identify potent small molecule anti-TB agents by machine learning, synthesis and biological evaluation. Methods: The On-line Chemical Database and Modeling Environment (OCHEM) was used to build predictive machine learning models. Seven compounds were synthesized and tested in vitro for their antitubercular activity against H37Rv and resistant Mtb strains. Results: A set of predictive models was built with OCHEM based on a set of previously synthesized isoniazid (INH) derivatives containing a thiazole core and tested against Mtb. The predictive ability of the models was tested by a 5-fold cross-validation, and resulted in balanced accuracies (BA) of 61–78% for the binary classifiers. Test set validation showed that the models could be instrumental in predicting anti- TB activity with a reasonable accuracy (with BA = 67–79 %) within the applicability domain. Seven designed compounds were synthesized and demonstrated activity against both the H37Rv and multidrugresistant (MDR) Mtb strains resistant to rifampicin and isoniazid. According to the acute toxicity evaluation in Daphnia magna neonates, six compounds were classified as moderately toxic (LD50 in the range of 10−100 mg/L) and one as practically harmless (LD50 in the range of 100−1000 mg/L). Conclusion: The newly identified compounds may represent a starting point for further development of therapies against Mtb. The developed models are available online at OCHEM http://ochem.eu/article/11 1066 and can be used to virtually screen for potential compounds with anti-TB activity.

FORMULATION DEVELOPMENT AND IN VITRO EVALUATION OF FLOATING TABLETS OF LAFUTIDINE BY EMPLOYING EFFERVESCENT TECHNOLOGY

2017 ◽  
Vol 5 (2) ◽  
pp. 26-44
Author(s):  
Vageesh N.M ◽  
◽  
Sri Sura Ramya ◽  
Begum K Gulijar ◽  
Swathi B ◽  
...  
Keyword(s):  
Formulation Development ◽  
In Vitro Evaluation ◽  
Floating Tablets

scholarly journals A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells

2021 ◽  
Author(s):  
Rashmi Kumari ◽  
Vasumathy R ◽  
Dhanya Sunil ◽  
Raghumani Singh Ningthoujam ◽  
Badri Narain Pandey ◽  
...  
Keyword(s):  
Fluorescence Imaging ◽  
Tumor Hypoxia ◽  
Binding Pocket ◽  
Docking Studies ◽  
Single Step ◽  
Naphthalic Anhydride ◽  
Hypoxic Conditions ◽  
Fluorescence Measurements ◽  
Enzymatic Reduction

AbstractThe bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4−(6−nitro−1,3−dioxo−1H−benzo[de]isoquinolin−2(3H)−yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4−nitro−1,8−naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR−aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF−7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions. Graphical abstract

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