Multivariate modelling for investigating the impact of raw materials and process variability on high drug load immediate release tablets obtained through wet granulation

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.

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Improved Dissolution Properties of Ketoconazole through Application of Liquisolid Techniques

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2015.8.4.9 ◽

2015 ◽

Vol 8 (4) ◽

pp. 3053-3059

Author(s):

Sudarshan Singh ◽

S S Shyale ◽

H G Sandip

Keyword(s):

Drug Release ◽

Immediate Release ◽

Water Soluble ◽

Wet Granulation ◽

Wetting Properties ◽

Enhanced Dissolution ◽

Water Soluble Drug ◽

Drug Concentrations ◽

Water Soluble Drugs ◽

Liquisolid Compacts

In present investigation liquisolid compact technique is investigated as a tool for enhanced dissolution of poorly water-soluble drug Ketoconazole. The liquisolid tablets were formulated with liquid medications, namely Propylene Glycol (PG) drug concentrations, 60% w/w, 70% w/w and 80% w/w. Avicel pH102 was used as a carrier material, Aerosil 200 as a coating material and Sodium starch glycollate as a super-disintegrant. Quality control tests, such as uniformity of tablet weight, uniformity of drug content, tablet hardness, friability test, disintegration and dissolution tests were performed to evaluate prepared tablets. For further confirmation of results the liquisolid compacts were evaluated by XRD and FTIR studies to prove that, solubility of Ketoconazole has been increased by liquisolid compact technique. From the results obtained, it was be speculated that such systems exhibit enhanced drug release profiles due to increased wetting properties and surface of drug available for dissolution. As liquisolid compacts demonstrated significantly higher drug release rates, in PG as compared to directly compressible tablets and conventional wet granulation, we lead to conclusion that it could be a promising strategy in improving the dissolution of poor water soluble drugs and formulating immediate release solid dosage forms.

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Оrganic Meat Production of Broiler Chickens Hubbard Redbro Cross

International Journal of Veterinary Science ◽

10.37422/ijvs/20.072 ◽

2020 ◽

Keyword(s):

Broiler Chickens ◽

Raw Materials ◽

Animal Health ◽

Meat Products ◽

Poultry Meat ◽

Meat Production ◽

Significant Difference ◽

Environmentally Safe ◽

The Impact

This article presents the results of studying the impact of housing and feeding conditions on broiler chickens of Hubbard RedBro cross, as well as the quality of products obtained when using floor and cage content, in a farm. It established that when receiving a mixed feed of own production using feed raw materials grown on a farm without the use of pesticides, a statistically significant decrease in potentially dangerous substances for animal health is recorded. Compared with factory feed, it has reduced the content of pesticides by 14 times, and mercury and arsenic by 24 times, cadmium by five times, and lead by ten times. The results of the study of economic indicators of growing Hubbard RedBro cross broiler chickens, as well as the chemical composition and quality of carcasses, indicated that there was no significant difference between the floor and cell conditions of keeping. Still, the use of a diet based on eco-feeds contributed to a statistically significant decrease in the concentration of toxic metals in the muscles of the poultry of the experimental groups. As a result, it found that the use of the studied compound feed in the diets of broiler chickens increased the indicators of Biosafety and ensured the production of environmentally safe ("organic") poultry meat products.

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Impact of Raw Materials and Processing Techniques on The Microbiological Quality of Egyptian Domiati Cheese

International Journal of Veterinary Science ◽

10.37422/ijvs/20.060 ◽

2020 ◽

Keyword(s):

Raw Materials ◽

Microbiological Quality ◽

Raw Milk ◽

Plate Count ◽

E Coli ◽

Fresh Cheese ◽

Processing Techniques ◽

The Impact ◽

Total Yeast

Domiati cheese is the most popular brand of cheese ripened in brine in the Middle East in terms of consumed quantities. This study was performed to investigate the impact of the microbiological quality of the used raw materials, the applied traditional processing techniques and ripening period on the quality and safety of the produced cheese. Three hundred random composite samples were collected from three factories at Fayoum Governorate, Egypt. Collected samples represent twenty-five each of: raw milk, table salt, calf rennet, microbial rennet, water, environmental air, whey, fresh cheese, ripened cheese & swabs from: worker hands; cheese molds and utensils; tanks. All samples were examined microbiologically for Standard Plate Count (SPC), coliforms count, Staphylococcus aureus (S. aureus) count, total yeast & mould count, presence of E. coli, Salmonellae and Listeria monocytogenes (L. monocytogenes). The mean value of SPC, coliforms, S. aureus and total yeast & mould counts ranged from (79×102 CFU/m3 for air to 13×108 CFU/g for fresh cheese), (7×102 MPN/ cm2 for tank swabs to 80×106 MPN/ml for raw milk), (9×102 CFU/g for salt to 69×106 CFU/g for fresh cheese) and (2×102 CFU/cm2 for hand swabs to 60×104 CFU/g for fresh cheese), respectively. Whereas, E. coli, Salmonella and L. monocytogenes failed to be detected in all examined samples. There were significant differences in all determined microbiological parameters (p ≤0.05) between fresh and ripened cheese which may be attributed to different adverse conditions such as water activity, pH, salt content and temperature carried out to improve the quality of the product.

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2-Piece Cork Stoppers as Alternative for Valorization of Thin Cork Planks: Analysis by LCA Methodology

Foods ◽

10.3390/foods10040873 ◽

2021 ◽

Vol 10 (4) ◽

pp. 873

Author(s):

Francisco Javier Flor-Montalvo ◽

Agustín Sánchez-Toledo Ledesma ◽

Eduardo Martínez Cámara ◽

Emilio Jiménez-Macías ◽

Jorge Luis García-Alcaraz ◽

...

Keyword(s):

Life Cycle Assessment ◽

Life Cycle ◽

Raw Materials ◽

Lca Methodology ◽

Significant Difference ◽

Different Dimensions ◽

The Impact ◽

Different Thickness ◽

Cork Stoppers ◽

Wine Bottle

Natural stoppers are a magnificent closure for the production of aging wines and unique wines, whose application is limited by the availability of raw materials and more specifically of cork sheets of different thickness and quality. The growing demand for quality wine bottle closures leads to the search for alternative stopper production. The two-piece stopper is an alternative since it uses non-usable plates in a conventional way for the production of quality caps. The present study has analyzed the impact of the manufacture of these two-piece stoppers using different methodologies and for different dimensions by developing an LCA (Life Cycle Assessment), concluding that the process phases of the plate, its boiling, and its stabilization, are the phases with the greatest impact. Likewise, it is detected that the impacts in all phases are relatively similar (for one kg of net cork produced), although the volumetric difference between these stoppers represents a significant difference in impacts for each unit produced.

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Process Modeling and Simulation of Tableting—An Agent-Based Simulation Methodology for Direct Compression

Pharmaceutics ◽

10.3390/pharmaceutics13070996 ◽

2021 ◽

Vol 13 (7) ◽

pp. 996

Author(s):

Niels Lasse Martin ◽

Ann Kathrin Schomberg ◽

Jan Henrik Finke ◽

Tim Gyung-min Abraham ◽

Arno Kwade ◽

...

Keyword(s):

Raw Materials ◽

Pilot Scale ◽

Physical Models ◽

Agent Based Simulation ◽

Validation Data ◽

Agent Based ◽

Industrial Processing ◽

Digital Twins ◽

Product And Process ◽

The Impact

In pharmaceutical manufacturing, the utmost aim is reliably producing high quality products. Simulation approaches allow virtual experiments of processes in the planning phase and the implementation of digital twins in operation. The industrial processing of active pharmaceutical ingredients (APIs) into tablets requires the combination of discrete and continuous sub-processes with complex interdependencies regarding the material structures and characteristics. The API and excipients are mixed, granulated if required, and subsequently tableted. Thereby, the structure as well as the properties of the intermediate and final product are influenced by the raw materials, the parametrized processes and environmental conditions, which are subject to certain fluctuations. In this study, for the first time, an agent-based simulation model is presented, which enables the prediction, tracking, and tracing of resulting structures and properties of the intermediates of an industrial tableting process. Therefore, the methodology for the identification and development of product and process agents in an agent-based simulation is shown. Implemented physical models describe the impact of process parameters on material structures. The tablet production with a pilot scale rotary press is experimentally characterized to provide calibration and validation data. Finally, the simulation results, predicting the final structures, are compared to the experimental data.

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Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process

Pharmaceutics ◽

10.3390/pharmaceutics13020210 ◽

2021 ◽

Vol 13 (2) ◽

pp. 210

Author(s):

Lise Vandevivere ◽

Maxine Vangampelaere ◽

Christoph Portier ◽

Cedrine de Backere ◽

Olaf Häusler ◽

...

Keyword(s):

Dissolution Kinetics ◽

Wet Granulation ◽

Continuous Manufacturing ◽

Formulation Development ◽

Granulation Process ◽

Low Viscosity ◽

Twin Screw ◽

Poorly Soluble ◽

Selection For ◽

The Impact

The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable efficient formulation development. Therefore, the current study identified binder attributes affecting the binder effectiveness in a wet granulation process of a highly soluble model excipient (mannitol). For this formulation, higher binder effectiveness was linked to fast activation of the binder properties (i.e., fast binder dissolution kinetics combined with low viscosity attributes and good wetting properties by the binder). As the impact of binder attributes on the granulation process of a poorly soluble formulation (dicalcium phosphate) was previously investigated, this enabled a comprehensive comparison between both formulations in current research focusing on binder selection. This comparison revealed that binder attributes that are important to guide binder selection differ in function of the solubility of the formulation. The identification of critical binder attributes in the current study enables rational and efficient binder selection for twin-screw granulation of well soluble and poorly soluble formulations. Binder addition proved especially valuable for a poorly soluble formulation.

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631 Sleep SMART in Adolescents with Neurodevelopmental Disorders

SLEEP ◽

10.1093/sleep/zsab072.629 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A247-A248

Author(s):

Alyson Hanish ◽

Abbey Jo Klein ◽

Therese Mathews ◽

Ann Berger ◽

Kevin Kupzyk ◽

...

Keyword(s):

Sleep Disturbance ◽

Neurodevelopmental Disorders ◽

Sleep Disturbances ◽

Immediate Release ◽

Sleep Time ◽

Normative Values ◽

Exogenous Melatonin ◽

Contingency Contracting ◽

Sleep Questionnaires ◽

The Impact

Abstract Introduction: Introduction Sleep disturbances are common in adolescents with neurodevelopmental disorders (NDDs). Inclusion of vulnerable populations such as adolescents with NDDs into sleep intervention efforts is essential as they are at high-risk for poor physical/mental health outcomes. The objective of this study is to pilot a sequential, multiple assignment, randomized trial (SMART) design to compare the impact of a sequence of sleep interventions, based on treatment response, to optimize sleep health in adolescents with NDDs. Methods: Methods Recruitment began June 2019 using convenience sampling. The SMART pilot feasibility study includes 1-week of baseline sleep data, and two 4-week periods of a sleep intervention (9-week total study enrollment). Interventions include exogenous melatonin, The Bedtime Bank, and their combination. Exogenous melatonin (liquid, immediate release, 3mg) is administered 30 minutes before bedtime. The Bedtime Bank, a behavioral sleep intervention, is based upon contingency contracting that relies on a credit- or debt-based system to hold adolescents accountable for maintaining a consistent bedtime. At baseline participants completed demographics, PROMIS pediatric sleep questionnaires, the Cleveland Adolescent Sleepiness Questionnaire (CASQ), salivary & urinary endogenous melatonin measurement, and one week of actigraphy. Upon enrollment, participants were randomly assigned to either melatonin or The Bedtime Bank. Participants who respond (nightly increase in total sleep time (TST) ≥18 minutes) remain on the assigned intervention; if non-responsive participants are re-randomized to a different sleep intervention or combination. Results: Results At baseline, participants (n=29, aged 10–18 years) had an average TST of 7 hours 11 minutes. PROMIS Sleep Disturbance (M=64.3, SE=2.5), PROMIS Sleep-Related Impairment scores (M=58.9, SE=2.2), and CASQ scores (M=40.0, SD= 10.5) were higher than reported normative values. Salivary DLMO & urinary 6-sulfatoyxmelatonin analysis is ongoing. For participants who completed the full 9-week trial, nearly 30% (n=7/24) were responsive (increased baseline TST ≥18 minutes) to one of the 4-week interventions. Conclusion: Conclusion Baseline data of the enrolled participants demonstrates poor indicators of TST, sleep disturbance, and sleep related impairment. Preliminary results of this SMART indicate some adolescents are responsive to sleep interventions aimed to improve their TST. Support (if any) Support: This clinical trial is funded by the National Institute of Nursing Research, National Institutes of Health (1K01NR017465-01A1).

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Modified Nanoclays/Straw Fillers as Functional Additives of Natural Rubber Biocomposites

Polymers ◽

10.3390/polym13050799 ◽

2021 ◽

Vol 13 (5) ◽

pp. 799

Author(s):

Justyna Miedzianowska ◽

Marcin Masłowski ◽

Przemysław Rybiński ◽

Krzysztof Strzelec

Keyword(s):

Natural Rubber ◽

Raw Materials ◽

Research Work ◽

Damping Properties ◽

Main Research ◽

Functional Additives ◽

Different Types ◽

Elastomeric Materials ◽

Research Goal ◽

The Impact

Increasingly, raw materials of natural origin are used as fillers in polymer composites. Such biocomposites have satisfactory properties. To ensure above-average functional properties, modifications of biofillers with other materials are also used. The presented research work aimed to produce and characterize elastomeric materials with a straw-based filler and four different types of montmorillonite. The main research goal was to obtain improved functional parameters of vulcanizates based on natural rubber. A series of composites filled with straw and certain types of modified and unmodified nano-clays in various ratios and amounts were prepared. Then, they were subjected to a series of tests to assess the impact of the hybrids used on the final product. It has been shown that the addition of optimal amounts of biofillers can, inter alia, increase the tensile strength of the composite, improve damping properties, extend the burning time of the material and affect the course of vulcanization or cross-linking density.

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