Accelerating pre-formulation investigations in early drug product lifecycle using predictive methodologies and computational algorithms

2021 ◽  
Author(s):  
Harsh S Shah ◽  
Kaushalendra Chaturvedi ◽  
Shanming Kuang ◽  
Jian Wang
Keyword(s):  
Case Studies ◽  
Drug Product ◽  
Analytical Techniques ◽  
Cost Effective ◽  
Product Lifecycle ◽  
Predictive Tools ◽  
Drug Products ◽  
Current Trends ◽  
Drug Substances ◽  
Early Drug

Precisely developed computational methodologies can allow the drug product lifecycle process to be time-efficient, cost-effective and reliable through a thorough fundamental understanding at the molecular level. Computational methodologies include computational simulations, virtual screening, mathematical modeling and predictive tools. In light of current trends and increased expectations of product discovery in early pharmaceutical development, we have discussed different case studies. These case studies clearly demonstrate the successful application of predictive tools alone or in combination with analytical techniques to predict the physicochemical properties of drug substances and drug products, thereby shortening research and development timelines. The overall goal of this report is to summarize unique predictive methodologies, which can assist pharmaceutical scientists in achieving time-sensitive research goals and avoiding associated risks that can potentially affect the drug product quality.

scholarly journals POLYMORPHISM AND POLYMORPH CHARACTERISATION IN PHARMACEUTICALS

2019 ◽  
Vol 8 (5) ◽  
Author(s):  
Dr Amit Gosar ◽  
Dr Sayyed Hussain ◽  
Dr Tabrez Shaikh
Keyword(s):  
Drug Product ◽  
Analytical Techniques ◽  
Spectroscopic Properties ◽  
Crystalline Form ◽  
Kinetic Properties ◽  
Specific Chemical ◽  
Safety And Efficacy ◽  
Drug Products ◽  
Drug Substances ◽  
The Given

Polymorphism is the ability of a specific chemical compound to crystallize in more than one crystalline form. Polymorphs had a different arrangement of the molecule in the given crystal lattice and  may properties such as packing properties, thermodynamic properties, spectroscopic properties, kinetic properties, surface properties and mechanical properties. Polymorph can be classified in various class such as crystalline, amorphous, hydrate and solvate. Polymorphs are categorized into two types, enantiotropes and monotropes, depending upon their stability with respect to the range of temperatures and pressures. There are various guidelines for the control of polymorphs in drug substances and drug product. Different analytical techniques are used for the detection, quantification and characterisation of the polymorphs in the drug substances and drug products. Control of polymorph in a drug substance and drug product is important for the safety and efficacy of the drug. Keywords: Polymorphism, classification, guidelines, characterisation, drug substances.

scholarly journals Innovative methodologies for identification and qualification of Impurities: An overview of the latest trends on impurity profiling

2020 ◽  
Vol 11 (3) ◽  
pp. 2909-2921
Author(s):  
Nishanth G ◽  
Akhila G ◽  
Anandkumar Tengli ◽  
Chandan R S ◽  
Suraj K ◽  
...  
Keyword(s):  
Pharmaceutical Research ◽  
Analytical Techniques ◽  
Pharmaceutical Formulations ◽  
Pharmaceutical Products ◽  
Analytical Methodology ◽  
Drug Products ◽  
Technical Developments ◽  
Drug Substances ◽  
Impurity Profiling ◽  
Bulk Drug

Impurity profiling is known to identify, classify and measure both the identified and non-identified contamination present on the medicinal product. Unwanted chemicals which remain or are created during the formulation of medicinal products are pharmaceutical impurities. Impurity profiling helps in the detection, recognition and quantification in bulk products and pharmaceutical formulations of various types of impurities, as well as residual solvents. It is the simplest way to distinguish consistency and stability of bulk drugs and medication formulations. As analytical methodology has developed rapidly, it is essential to consider with their solutions problems related to impurities of drug substances and drug products. Various regulatory agencies including ICH, USFDA, Canadian Drug and Health Agencies stress the criteria for purity and for detecting impurities in active pharmaceutical materials, even in small quantities, as the presence of impurities, may have an effect on pharmaceutical products ’ efficacy and health. Therefore, the study focuses on various analytical methods for identification and quantification of impurities in pharmaceutical products to clarify the need for impurity profiling on drug products in pharmaceutical research. To drug regulators, the product substance’s impurity profile is a reliable fingerprint to prove that the manufacturing process of bulk drug substances is consistent in quality. The study gives a short summary of recent technical developments in the profiling of pharmaceutical products including pharmaceutical active ingredients as well as pharmaceutical products during 2013-2017. Such recent trends in the profiling of impurities have been addressed in the study. This focuses specifically on a thorough update on various analytical techniques, including hyphenated methods to define and measure thresholds in specific pharmaceutical matrices of impurities and degradants.

Contamination Troubleshooting Approach from Problem to Solution

2019 ◽  
Author(s):  
Victor K. F. Chia ◽  
Hugh E. Gotts ◽  
Fuhe Li ◽  
Mark Camenzind
Keyword(s):  
Case Studies ◽  
Semiconductor Devices ◽  
Analytical Techniques ◽  
General Knowledge ◽  
Contamination Source ◽  
Root Cause ◽  
Sources Of Contamination

Abstract Semiconductor devices are sensitive to contamination that can cause product defects and product rejects. There are many possible types and sources of contamination. Root cause resolution of the contamination source can improve yield. The purpose of contamination troubleshooting is to identify and eliminate major yield limiters. This requires the use of a variety of analytical techniques[1]. Most important, it requires an understanding of the principle of contamination troubleshooting and general knowledge of analytical tests. This paper describes a contamination troubleshooting approach with case studies as examples of its application.

scholarly journals Microgrid as a Cost-Effective Alternative to Rural Network Underground Cabling for Adequate Reliability

Energies ◽  
2018 ◽  
Vol 11 (8) ◽  
pp. 1978 ◽  
Author(s):  
Sanna Uski ◽  
Erkka Rinne ◽  
Janne Sarsama
Keyword(s):  
Case Studies ◽  
Power Supply ◽  
Dairy Farm ◽  
Cost Effective ◽  
Distribution Networks ◽  
Comparison Method ◽  
Economic Benefits ◽  
Economic Feasibility ◽  
Cost Calculation ◽  
Islanded Operation

Microgrids can be used for securing the supply of power during network outages. Underground cabling of distribution networks is another effective but conventional and expensive alternative to enhance the reliability of the power supply. This paper first presents an analysis method for the determination of microgrid power supply adequacy during islanded operation and, second, presents a comparison method for the overall cost calculation of microgrids versus underground cabling. The microgrid power adequacy during a rather long network outage is required in order to indicate high level of reliability of the supply. The overall cost calculation considers the economic benefits and costs incurred, combined for both the distribution network company and the consumer. Whereas the microgrid setup determines the islanded-operation power adequacy and thus the reliability of the supply, the economic feasibility results from the normal operations and services. The methods are illustrated by two typical, and even critical, case studies in rural distribution networks: an electric-heated detached house and a dairy farm. These case studies show that even in the case of a single consumer, a microgrid option could be more economical than network renovation by underground cabling of a branch in order to increase the reliability.

scholarly journals Innovating on Inhaled Bioequivalence: A Critical Analysis of the Current Limitations, Potential Solutions and Stakeholders of the Process

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1051
Author(s):  
Jonattan Gallegos-Catalán ◽  
Zachary Warnken ◽  
Tania F. Bahamondez-Canas ◽  
Daniel Moraga-Espinoza
Keyword(s):  
New Technologies ◽  
Innovation Process ◽  
Cost Effective ◽  
Regulatory Agencies ◽  
Drug Products ◽  
Effective Strategies ◽  
Rate Analysis ◽  
Orally Inhaled Drug Products ◽  
Next Generation Impactor ◽  
First Time

Orally inhaled drug products (OIDPs) are an important group of medicines traditionally used to treat pulmonary diseases. Over the past decade, this trend has broadened, increasing their use in other conditions such as diabetes, expanding the interest in this administration route. Thus, the bioequivalence of OIDPs is more important than ever, aiming to increase access to affordable, safe and effective medicines, which translates into better public health policies. However, regulatory agencies leading the bioequivalence process are still deciding the best approach for ensuring a proposed inhalable product is bioequivalent. This lack of agreement translates into less cost-effective strategies to determine bioequivalence, discouraging innovation in this field. The Next-Generation Impactor (NGI) is an example of the slow pace at which the inhalation field evolves. The NGI was officially implemented in 2003, being the last equipment innovation for OIDP characterization. Even though it was a breakthrough in the field, it did not solve other deficiencies of the BE process such as dissolution rate analysis on physiologically relevant conditions, being the last attempt of transferring technology into the field. This review aims to reveal the steps required for innovation in the regulations defining the bioequivalence of OIDPs, elucidating the pitfalls of implementing new technologies in the current standards. To do so, we collected the opinion of experts from the literature to explain these trends, showing, for the first time, the stakeholders of the OIDP market. This review analyzes the stakeholders involved in the development, improvement and implementation of methodologies that can help assess bioequivalence between OIDPs. Additionally, it presents a list of methods potentially useful to overcome some of the current limitations of the bioequivalence standard methodologies. Finally, we review one of the most revolutionary approaches, the inhaled Biopharmaceutical Classification System (IBCs), which can help establish priorities and order in both the innovation process and in regulations for OIDPs.

scholarly journals Current trends and advances in analytical techniques for the characterization and quantification of biologically recalcitrant organic species in sludge and wastewater: A review

2021 ◽  
Vol 1152 ◽  
pp. 338284
Author(s):  
Sylvain Faixo ◽  
Nicolas Gehin ◽  
Stéphane Balayssac ◽  
Véronique Gilard ◽  
Sofiane Mazeghrane ◽  
...  
Keyword(s):  
Analytical Techniques ◽  
Organic Species ◽  
Current Trends

scholarly journals DNA aptamer-based detection of prostate cancer

2015 ◽  
Vol 69 (1) ◽  
Author(s):  
Pawan Jolly ◽  
Nello Formisano ◽  
Pedro Estrela
Keyword(s):  
Prostate Cancer ◽  
Point Of Care ◽  
Specific Antigen ◽  
Analytical Techniques ◽  
Cost Effective ◽  
Dna Aptamer ◽  
Clinical Samples ◽  
Gradual Transition ◽  
Long Term Stability ◽  
Promising Tool

AbstractThe use of aptamers in biosensing has attracted considerable attention as an alternative to antibodies because of their unique properties such as long-term stability, cost-effectiveness and adjustability to various applications. Among cancers, the early diagnosis of prostate cancer (PCa) is one of the greatest concerns for ageing men worldwide. One of the most commonly used biomarkers for PCa is prostate-specific antigen (PSA), which can be found in elevated levels in patients with cancer. This review presents the gradual transition of research from antibody-based to aptamerbased biosensors, specifically for PSA. A brief description on aptamer-based biosensing for other PCa biomarkers is also presented. Special attention is given to electrochemical methods as analytical techniques for the development of simple, sensitive and cost-effective biosensors. The review also focuses on the different surface chemistries exploited for fabrication and their applications in clinical samples. The use of aptamers represents a promising tool for the development of point-ofcare biosensors for the early detection of prostate cancer. In view of the unmatched upper hand of aptamers, future prospects are also discussed, not only in the point-of-care format but also in other novel applications.

Mature Field Economic Rejuvenation with Infill and Re-Entry Multilateral Well Creation Techniques

2021 ◽  
Author(s):  
Benjamin Butler ◽  
Justin Roberts ◽  
Matthew Kelsey ◽  
Steffen Van Der Veen
Keyword(s):  
Case Studies ◽  
Field Performance ◽  
Cost Effective ◽  
High Water ◽  
Additional Time ◽  
Flow Management ◽  
Performance Improvements ◽  
Mature Field ◽  
Water Cut ◽  
Time Required

Abstract Multilateral wells have been proven over decades and have developed into a reliable and cost effective approach to mature field rejuvenation and extended commercial viability. This paper will discuss case studies demonstrating a number of techniques used to create infill multilateral wells in existing fields with a high level of reliability and repeatability. Techniques reviewed will cover cutting and pulling production casing to drill and case a new mainbore versus sidetracking and adding laterals to an existing mainbore. Discussion will also cover completion designs that tie new laterals into existing production casing providing significantly greater reservoir contact. Temporary isolation of high water-cut laterals brought into production later in the well's life through bespoke completion designs will also be discussed. Case studies will include discussion of workover operations, isolation methods, and lateral creation systems. Where available, resulting field performance improvements will also be discussed. In Norway, slot recoveries are commonly performed by cutting and pulling the 10-3/4" casing, redrilling a new mainbore, and running new casing. This enables junction placement closer to unswept zones and easier lateral drilling to targets. It does have drawbacks, however, related to the additional time required to pull the subsea xmas tree and challenges associated with pulling casing. In 2019, Norway successfully completed a 10-3/4" retrofit installation, whereas a sidetrack was made from the 10-3/4" and an 8-5/8" expandable liner was run down into the reservoir pay zone where two new laterals were created. The 8-5/8" liner saved time otherwise spent having to drill the section down to the payzone from the laterals. These wells have a TAML Level 5 isolated junction, Autonomous Inflow Control Devices (AICDs) in each lateral, and an intelligent completion interface across the junction, enabling active flow management and monitoring of both branches. In Asia, infill laterals were added to existing wellbores by sidetracking 9-5/8" casing and tying production back to the original mainbore. These dual laterals were completed with intelligent completions to enable lateral flow management and monitoring of both laterals. In Australia, dual laterals were created in a similar fashion; laterals are added to existing wells; however, a novel approach was used to manage water from existing lower mainbore laterals whereby they are shut in at completion and opened later when the new lateral is watered out. The older lateral now produces at lower water cut given the time allowed for water coning in the lateral to relax. Using this practice, production is alternated back and forth between the two laterals. In the Middle East, an older well has been converted from TAML Level 4 to Level 5 in order to prevent detected gas migrating into the mainbore at the junction. This conversion of a cemented junction well has enabled production to resume on this well. The well was converted to incorporate an intelligent completion to enable flow control of each lateral. This paper intends to provide insights into the various mature field re-entry methods for multilateral well construction, and a review of the current technology capabilities and well designs through the review of multiple case histories.

Case Studies Highlighting Rapid Repair Methods of Pressurised Pipelines Damaged by Anchors

2018 ◽  
Author(s):  
Dale Millward
Keyword(s):  
Case Studies ◽  
Health And Safety ◽  
Cost Effective ◽  
Pipeline System ◽  
Subsea Pipeline ◽  
Damage Scenarios ◽  
Fail Safe ◽  
Subsea Pipelines ◽  
Marine Vessels ◽  
Pipeline Design

Effective pipeline design and regular maintenance can assist in prolonging the lifespan of subsea pipelines, however the presence of marine vessels can significantly increase the risk of pipeline damage from anchor hazards. As noted in the Health and Safety Executive – Guideline for Pipeline Operators on Pipeline Anchor Hazards 2009. “Anchor hazards can pose a significant threat to pipeline integrity. The consequences of damage to a pipeline could include loss of life, injury, fire, explosion, loss of buoyancy around a vessel and major pollution”. This paper will describe state of the art pipeline isolation tooling that enables safe modification of pressurised subsea pipelines. Double Block and Bleed (DBB) isolation tools have been utilised to greatly reduce downtime, increase safety and maximise unplanned maintenance, providing cost-effective solutions to the end user. High integrity isolation methods, in compliance with international subsea system intervention and isolation guidelines (IMCA D 044 / IMCA D 006), that enable piggable and unpiggable pipeline systems to be isolated before any breaking of containment, will also be explained. This paper will discuss subsea pipeline damage scenarios and repair options available to ensure a safe isolation of the pipeline and contents in the event of an incident DNV GL type approved isolation technology enables the installation of a fail-safe, DBB isolation in the event of a midline defect. The paper will conclude with case studies highlighting challenging subsea pipeline repair scenarios successfully executed, without depressurising the entire pipeline system, and in some cases without shutting down or interrupting production.

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