Robust Quality Audits Are The Solution To Avoiding Expensive Recalls

Compliance is an affirmative indication or judgement that the supplier of a product or service has met the requirements of the relevant specifications, contract or regulation; also the state of meeting the requirements. Compliance is something that meets both the text and the spirit of a requirement. This is the central message of the book Audit and Control for Healthcare Manufacturers” by Tim and Jennifer Sandle (published by DHI, http://www. dhibooks.com/books/17351.html)

Robust Quality Audits Are T... 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

How New Technologies are Revolutionizing Physical Therapy

The healthcare industry is experiencing rapid change as a result of new technologies. With physical therapy being one field that is seeing some of the most significant changes, patient care is getting more efficient and more effective.

We now see robotics becoming more common in a physical therapy setting, and patients can now use a range of tools that can be accessed from a smartphone or tablet. The technological tools are enabling direct access to physical therapy in New Jersey and other states across the nation. These advancements will provide patients with improved outcomes and physical therapy professionals will be able to achieve better results in less time.

With the latest tech on the horizon, patients and physical therapists can expect a much brighter future for rehabilitation services. The following are four of the trends that are helping to shape the future of patient care in physical therapy.

Apps for Physical Therapy

Smartphones and tablets have changed the modern world in a number of ways. We are now seeing smartphones moving into healthcare and that includes physical therapy. You have apps that can help patients with their physical therapy exercises. Beyond that, there are diagnostic tools that can be used on a phone and apps that help patients connect with physical therapy professionals.

One example is the Sway Medical app. This FDA-cleared app uses the sensors on a smartphone to perform tests for balance and reaction time. This can provide medical professionals with an easy way to test and get information on patients who have suffered some type of head injury.
Robotics

Different robotic systems are now showing great promise in physical therapy. One example is treadmills that use robotic legs to assist with gait training. With these systems, a harness holds the patient and a pair of robotic legs will help them walk.

As an extension of robotics, you also have exoskeletons that are helping patients relearn how to walk. Consider the ReWalk exoskeleton as an example. This lightweight exoskeleton can help the patient stand, sit, walk and turn. Some models can even climb stairs.

PT on a Gaming Console

Some physical therapists have been using video games for PT for some time. Much of this started with the Nintendo Wii, but it has gotten even better as video game technology has improved. With a device like the Microsoft Kinect, the motion-capture sensors allow the patient to move in a way that fits better with real-world movement. Games are even being designed specifically for the purposes of creating a better and more effective physical therapy experience.

PT in VR

Virtual reality is almost an extension of video games in physical therapy. When using VR for physical therapy, programs can be created to put the patient in a more pleasant environment. Developers can even make games that will encourage the patient to do various physical therapy exercises. With the right VR gear, the system can also collect data and track the patient’s progress.

These technologies are doing a lot of good in the physical therapy industry. Patients are seeing better outcomes than could have been expected in the past and PT professionals are able to help more patients with their time. These are significant benefits that are only going to increase as these technologies develop and become more accessible.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

How mucosal infections can rewire an immune response to shape susceptibility to recurrence

A new study, published today in eLife.

The findings in mice reveal how mucosal infections, specifically bladder infections, can rewire inflammatory responses driven by a protein called tumour necrosis factor-alpha (TNFɑ) to impact susceptibility to recurrence. These results could inform the development of more effective new treatment strategies.

Scientists have shed new light on how mucosal infections can affect the body’s inflammatory response to shape susceptibility to recurrence.

Their study in mice reveals how recurrent mucosal infections, specifically bladder infections, can rewire inflammatory responses driven by a protein called tumour necrosis factor-alpha (TNFɑ) to impact susceptibility. The findings, published in eLife, could inform the development of effective new treatment strategies.

Mucosal bacterial infections, which include urinary tract infections (UTIs), are common. In the US alone, they account for over 42m outpatient visits and most of the 270m antibiotic prescriptions given to outpatients annually. Over 80% of UTIs are caused by uropathogenic Escherichia coli (UPEC), and the vast majority of these infections cause bladder infection. Previous data from female patients, who are disproportionately affected, suggest that their disease history may impact the nature of how UPEC interacts with their urinary tract mucosa, altering their susceptibility to future episodes.

For further details, see: eLife

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Biocontamination Control for Pharmaceuticals and Healthcare

A new book has been published – “Biocontamination Control for Pharmaceuticals and Healthcare” by written Tim Sandle. The book outlines a biocontamination strategy that tracks bio-burden control and reduction at each transition in classified areas of a facility. This key part of controlling risk escalation can lead to the contamination of medicinal products, hence necessary tracking precautions are essential. Regulatory authorities have challenged pharmaceutical companies, healthcare providers, and those in manufacturing practice to adopt a holistic approach to contamination control. New technologies are needed to introduce barriers between personnel and the environment, and to provide a rapid and more accurate assessment of risk. This book offers guidance on building a complete biocontamination strategy.

Biocontamination Control fo... by Tim Sandle on Scribd

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Bacteria must be 'stressed out' to divide

A new study from EPFL scientists has found that bacteria use mechanical forces to divide, along with biological factors. The research, led by the groups of John McKinney and Georg Fantner at EPFL, came after recent studies suggested that bacterial division is not only governed by biology, but also by physics. However, this interplay is poorly understood.

Most bacteria are rod-shaped cells that multiply by doubling their length and dividing in the middle to yield two "daughter cells." Mechanisms that control these processes in space and time are critical for survival. The importance of these mechanisms becomes even clearer, given how pervasive bacteria are in everyday life, and how ubiquitous their use is in biotechnology.

The scientists studied bacteria that are very similar to the human pathogen that causes tuberculosis, which kills more people than any other infectious disease. To study the growth and division dynamics of these "mycobacteria" the scientists built a special instrument that combines optical and atomic force microscopy (AFM) to image and manipulate cells at the size scale of molecules.

The data showed that mycobacterial cell division requires mechanical forces in addition to previously identified division molecules (enzymes). Before a cell divides, there is a progressive build-up of mechanical stress in the cell wall, right at the point where the cell will divide.

The build-up eventually culminates in a millisecond-fast splitting of the cell into two new cells. Remarkably, when the researchers physically pressed on the bacteria with an ultra-sharp AFM needle, they caused instantaneous and premature cell division.

But where is the biological part of the story? When a bacterial cell divides the two daughters must separate, a process mediated by enzymes that dissolve the molecular connections between them. The investigators found that this essential process could be bypassed by pressing on the nascent division site using the AFM needle.

See:

Pascal D. Odermatt, Mélanie T. M. Hannebelle, Haig A. Eskandarian, Adrian P. Nievergelt, John D. McKinney, Georg E. Fantner. Overlapping and essential roles for molecular and mechanical mechanisms in mycobacterial cell division. Nature Physics, 2019 DOI: 10.1038/s41567-019-0679-1

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Understanding enzymes that make antibiotic for drug-resistant pathogen

One of the WHO's three critical priority pathogens, Acinetobacter baumannii, for which new antibiotics are urgently needed is one step closer to being tackled, as researchers from the Department of Chemistry -- University of Warwick have made a breakthrough in understanding the enzymes that assemble the antibiotic enacyloxin.

Acinetobacter baumannii is a pathogen that causes hospital-acquired infections that are very difficult to treat, because they are resistant to most currently available antibiotics.

In a previous paper, researchers at the University of Warwick and Cardiff University showed that a molecule called enacyloxin is effective against Acinetobacter baumannii. However, the molecule needs to be engineered to make it suitable for treating infections caused by the pathogen in humans.

The first step to achieving this is to understand the molecular mechanisms used to assemble enacyloxin by the bacterium that makes it. In their paper 'A dual transacylation mechanism for polyketide synthase chain release in enacyloxin antibiotic biosynthesis' published in the journal Nature Chemistry, the researchers identify the enzymes responsible for joining the two components of the antibiotic together.

The key enzyme in this process was found to be promiscuous, suggesting it could be harnessed to produce structurally modified versions of the antibiotic.

See:

Simone Kosol, Angelo Gallo, Daniel Griffiths, et al. Structural basis for chain release from the enacyloxin polyketide synthase. Nature Chemistry, 2019; DOI: 10.1038/s41557-019-0335-5

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

New class of antibiotic candidates profiled

The novel small molecules, based on new target, new chemical structure and new antimicrobial mechanism, are different from those of existing antibiotics. The new drug candidates demonstrate much effective abilities of inhibiting bacterial growth than commonly used antibiotics, yet with no toxicity to human cells.

The development of "Nusbiarylins," a new class of antimicrobial agents, by the research team of the State Key Laboratory of Chemical Biology and Drug Discovery of PolyU's Department of Applied Biology and Chemical Technology (ABCT), is thus a breakthrough in the battle against multi-drug resistant bacterial infections.

The researchers developed a model basing on the structure of NusB and NusE, and applied computer-aided screening to screen about 5,000 small molecule compounds with drug-like properties to explore for inhibitors for NusB-NusE interaction. The shortlisted compounds were then put to tests for antimicrobial activity against different MRSA strains. A compound, (E)-2-{[(3-ethynylphenyl)imino]methyl}-4-nitrophenol (hereafter addressed as MC4), was identified as having much effective antibacterial abilities than the commonly used antibiotics. The Minimum Inhibitory Concentration (note: MIC denotes the lowest concentration of a chemical/drug for preventing bacterial growth) of MC4 for some MRSA strains are as low as 8 ?g/mL, compared to the MICs of >64 ?g/mL demonstrated by two antibiotics in the market, oxacillin and gentamicin.

Test of MC4 on human lung and skin cells (infections caused by MRSA often occur in these tissues) indicated no significant toxicity. The fact that NusB and NusE exist only in bacteria and not human cells has also addressed toxicity concern.

The research team has further structurally modified MC4 for optimization, and 167 analogues were synthesized so far. The new class of compounds are named as "Nusbiarylins" (basing on their target protein "NusB" and their "biaryl" structure). Laboratory test of Nusbiarylins against a panel of MRSA strains proved their consistent antibacterial activity, some with MIC as low as 0.125 ?g/mL, much better than commonly used antibiotics, including vancomycin with the MIC of 1 ?g/mL which is labelled as the "last resort" antibiotic drug in the United States.

Further pre-clinical studies on the in vitro pharmacological properties of Nusbiarylins on human cells indicated that the compounds: leading to nearly no hemolysis (i.e. human blood cell breaking), an indication of being safe for injection; and with excellent result in intestine absorption, implying being effective for oral taking.

See:

Yangyi Qiu, Shu Ting Chan, Lin Lin, et al Nusbiarylins, a new class of antimicrobial agents: Rational design of bacterial transcription inhibitors targeting the interaction between the NusB and NusE proteins. Bioorganic Chemistry, 2019; 92: 103203 DOI: 10.1016/j.bioorg.2019.103203

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

New fungus-derived antibiotic identified

Immunodeficiency is the condition where the capability of the immune system to fight against diseases has been compromised. Immunocompromised people have a higher chance of contacting diseases compared to people with healthy immune systems. Immunodeficiency usually occurs as a consequence of several factors, such as diseases like AIDS and diabetes, chemotherapy, and organ transplant. Recently, doctors have noted an increased trend in the occurrence of life-threatening fungal infections -- also called mycoses -- in immunocompromised patients. In such cases, treatment requires the use of some special compounds with antifungal properties. Unfortunately, antifungal drugs currently available are very limited.

In 2006, a lead compound "eushearilide," derived from fungi, was discovered. It was found to have antifungal and antiyeast properties, and could tackle several fungi that were known to cause infections in humans.

For the study at Tokyo University of Science, first, usharelide had to be derived from eushearilide. This was achieved through a set of reactions involving the alteration of molecules attached at the 23rd carbon atom of eushearilide. Once usharelide and its structural variations were derived, they were tested for their antibiotic properties, specifically against fungi and bacteria. The researchers found that these compounds had significant promising antibiotic properties. In particular, two of the several variations of usharelide showed antimicrobial properties against Candida albicans, a fungus that is the instigator of yeast infections. Meanwhile, most of the variations showed antimicrobial properties against Cryptococcus neoformans, which causes lung infections, meningitis, and encephalitis, particularly in AIDS patients. This finding echoed the previous findings on the antifungal properties of eushearilide. However, what was even more interesting is that these usharelide variations also showed good antibacterial properties against several disease-causing bacterial species, including methicillin-resistant Staphylococcus aureus (MRSA), which is known to be a particularly difficult bacterium to tackle due to its resistance to several antibiotics and causes potentially fatal infections, particularly in people with weak immune systems.

These findings emphasize the unique status and importance of eushearilide and its derivative usharelide in the treatment of several fungal diseases in immunocompromised people. More significantly, these findings also shed light on the possible antibacterial properties of these compounds, which have not been adequately explored in research before. Usharelide has the potential for application in the treatment for patients with fungal diseases such as candidiasis, and in the elimination of hospital-origin infections caused by MRSA and vancomycin-resistant enterococci.

This study definitely promises to be a step in the right direction for treating recalcitrant infections in immunocompromised people caused by dangerously pathogenic bacteria, which were once thought to be unconquerable.

See:

Takayuki Tonoi, Takehiko Inohana, Teruyuki Sato, et al Total Synthesis and Antimicrobial Evaluation of 23-Demethyleushearilide and Extensive Antimicrobial Evaluation of All Synthetic Stereoisomers of (16Z,20E)-Eushearilide and (16E,20E)-Eushearilide. Molecules, 2019; 24 (19): 3437 DOI: 10.3390/molecules24193437

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Scientists find microbial remains in ancient rocks

Scientists have found exceptionally preserved microbial remains in some of Earth's oldest rocks in Western Australia -- a major advance in the field, offering clues for how life on Earth originated.

The UNSW researchers found the organic matter in stromatolites -- fossilised microbial structures -- from the ancient Dresser Formation in the Pilbara region of Western Australia.

The stromatolites have been thought to be of biogenic origin ever since they were discovered in the 1980s. However, despite strong textural evidence, that theory was unproven for nearly four decades, because scientists hadn't been able to show the definitive presence of preserved organic matter remains – until now.

Stromatolites in the Dresser Formation are usually sourced from the rock surface, and are therefore highly weathered. For this study, the scientists worked with samples that were taken from further down into the rock, below the weathering profile, where the stromatolites are exceptionally well preserved. Using a variety of cutting-edge micro-analytical tools and techniques -- including high-powered electron microscopy, spectroscopy and isotope analysis – the researchers examined the rocks.

This showed exceptionally preserved coherent filaments and strands that are typically remains of microbial biofilms.

See:

Raphael J. Baumgartner, Martin J. Van Kranendonk, David Wacey, Marco L Fiorentini, Martin Saunders, Stefano Caruso, Anais Pages, Martin Homann, Paul Guagliardo. Nano−porous pyrite and organic matter in 3.5-billion-year-oldstromatolites record primordial life. Geology, 2019; DOI: 10.1130/G46365.1

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

ISO 14644-16:2019 – Part 16: Energy efficiency in cleanrooms and separative devices

A new standard has been issued:

“This document gives guidance and recommendations for optimizing energy usage and maintaining energy efficiency in new and existing cleanrooms, clean zones and separative devices. It provides guidance for the design, construction, commissioning

and operation of cleanrooms.

This document covers all cleanroom-specific features and can be used in different areas to optimize energy use in electronic, aerospace, nuclear, pharmaceutical, hospital,

medical device, food industries and other clean air applications.

It also introduces the concept of benchmarking for the performance assessment and comparison of cleanroom energy efficiencies, while maintaining performance levels to ISO 14644 requirements.

See: https://www.iso.org/standard/66331.html

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Robust Quality Audits Are The Solution To Avoiding Expensive Recalls

Audit and Control for Healthcare Manufacturers” by Tim and Jennifer Sandle (published by DHI, http://www.dhibooks.com/books/17351.html)

Robust Quality Audits Are T... by Tim Sandle on Scribd

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

New cause of antibiotic resistance identified

Bacteria can change form in human body, hiding the cell wall inside themselves to avoid detection. The cell wall is often the antibiotic target - so if bacteria are concealing it inside themselves antibiotics have no target. New osmoprotective detection methods are needed to be used to identify any L-form bacteria. Research also showed that L-form bacteria can revert back to walled bacteria - within 5 hours.

Scientists have confirmed for the first time that bacteria can change form to avoid being detected by antibiotics in the human body. Studying samples from elderly patients with recurring urinary tract infections, the Newcastle University team used state-of-the art techniques to identify that a bacteria can lose its cell wall -- the common target of many groups of antibiotics.

The research by the Errington lab which turns on its head current thinking about the bacteria's ability to survive without a cell wall, known as "L-form switching," is published today in Nature Communications. The World Health Organisation has identified antibiotic resistance as one of the biggest threats to global health, food security, and development today.

Lead author, Dr Katarzyna Mickiewicz researcher at Newcastle University said: "Imagine that the wall is like the bacteria wearing a high-vis jacket. This gives them a regular shape (for example a rod or a sphere), making them strong and protecting them but also makes them highly visible -- particularly to human immune system and antibiotics like penicillin.

"What we have seen is that in the presence of antibiotics, the bacteria are able to change from a highly regular walled form to a completely random, cell wall-deficient L-form state- in effect, shedding the yellow jacket and hiding it inside themselves. "In this form the body can't easily recognise the bacteria so doesn't attack them -- and neither do antibiotics."

See:

Katarznya Mickiewicz et al. Possible role of L-form switching in recurrent urinary tract infection. Nature Communications, 2019 DOI: 10.1038/s41467-019-12359-3

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

High-speed microscope illuminates biology

The Columbia team behind the revolutionary 3D SCAPE microscope announces today a new version of this high-speed imaging technology. In collaboration with scientists from around the world, they used SCAPE 2.0 to reveal previously unseen details of living creatures -- from neurons firing inside a wriggling worm to the 3D dynamics of the beating heart of a fish embryo, with far superior resolution and at speeds up to 30 times faster than their original demonstration.

These improvements to SCAPE promise to impact fields as wide ranging as genetics, cardiology and neuroscience.

Although imaging samples using sheets of light date back more 100 years, SCAPE's ingenuity lies in the way that it rapidly moves the light sheet and focuses the image of this sheet back to a stationary camera using a single moving mirror -- making it lightning fast and surprisingly simple. In addition, SCAPE is gentle on living samples because it uses only a fraction of the light that point-scanning microscopes would need to get images at comparable speeds. SCAPE achieves all this through a single, stationary objective lens, opening up space for a wide array of samples compared to conventional light-sheet microscopes that require complex sample chambers surrounded by many lenses.

SCAPE 2.0's improved resolution also enabled the team to image samples created using tissue clearing and tissue expansion. These methods let scientists see structures and connections deep inside intact samples, from whole mouse brains to tumors and human biopsies. Although these samples are not alive, they are very large and take a long time to image using standard microscopes. Today's paper demonstrates that SCAPE 2.0 could image these types of samples at record-breaking speeds. The researchers worked with Lambert Instruments, leveraging the company's ultra-fast HiCAM Fluo camera. This camera was used to capture images at more than 18,000 frames per second in the zebrafish embryo's beating heart. This new configuration opened the door to recording individual neurons firing in a freely moving C. elegans worms, giving the first view of an animal's complete nervous system in action. SCAPE 2.0's other upgrades include improved light efficiency, a larger field of view and much improved spatial resolution.

See:

Venkatakaushik Voleti, Kripa B. Patel, Wenze Li, et al. Real-time volumetric microscopy of in-vivo dynamics and large-scale samples with SCAPE 2.0. Nature Methods, 2019 DOI: 10.1038/s41592-019-0579-4

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Just how many pathogens are lurking in your washing machine?

Investigators have identified a washing machine as a reservoir of multidrug-resistant pathogens. The pathogens, a single clone of Klebsiella oxytoca, were transmitted repeatedly to newborns in a neonatal intensive care unit at a children's hospital. The transmission was stopped only when the washing machine was removed from the hospital.

The research has implications for household use of washers. Water temperatures used in home washers have been declining, to save energy, to well below 60°C (140°F), rendering them less lethal to pathogens. Resistance genes, as well as different microorganisms, can persist in domestic washing machines at those reduced temperatures, according to the report.

At the hospital where the washing machine transmitted K. oxytoca, standard screening procedures revealed the presence of the pathogens on infants in the ICU. The researchers ultimately traced the source of the pathogens to the washing machine, after they had failed to find contamination in the incubators or to find carriers among healthcare workers who came into contact with the infants.

The newborns were in the ICU due mostly to premature birth or unrelated infection.The clothes that transmitted K. oxytoca from the washer to the infants were knitted caps and socks to help keep them warm in incubators, as newborns can quickly become cold, even in incubators.

The investigators assume that the pathogens "were disseminated to the clothing after the washing process, via residual water on the rubber mantle [of the washer] and/or via the final rinsing process, which ran unheated and detergent-free water through the detergent compartment," implicating the design of the washers, as well as the low heat, according to the report. The study implies that changes in washing machine design and processing are required to prevent the accumulation of residual water where microbial growth can occur and contaminate clothes.

However, it still remains unclear how, and via what source the pathogens got into the washing machine. The infants in the intensive care units (ICU) were colonized, but not infected by K. oxytoca.

See: https://scitechdaily.com/warning-your-energy-efficient-washing-machine-could-be-harboring-dangerous-pathogens/

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

The Use of Microbiological Culture Media Article

Free-to-read article on microbial culture media best practices.

The Use of Microbiological ... by Tim Sandle on Scribd

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

E. coli detected in minutes by new technology

A discovery by researchers at the School of Life Sciences at the University of Warwick offers a new technology for detecting bacteria in minutes by 'zapping' the bacteria with electricity.

Testing clinical samples or commercial products for bacterial contamination typically takes days. During this time, they can cause significant damage; many infections can become life threatening very quickly if not identified and treated with appropriate antibiotics.

For example, 8% of people with severe blood infection sepsis will die for every hour of delay in proper treatment. More routine problems like urinary tract infections are difficult to diagnose and some people cannot get a clear answer about their symptoms due to difficulties with detecting low-level infections. Studies have found 20-30% of urinary tract infections are missed by dipstick tests used for detecting bacteria in the urine.

Scientists have discovered that healthy bacteria cells and cells inhibited by antibiotics or UV light showed completely different electric reactions. They made this discovery by combining biological experiments, engineering and mathematical modelling. The findings could lead to the development of medical devices which can rapidly detect live bacterial cells, evaluate the effects of antibiotics on growing bacteria colonies, or which could identify different types of bacteria and reveal antibiotic-resistant bacteria.

The researchers have an ambitious plan to deliver the technology to market to maximise social good and have founded a start-up company Cytecom to commercialise the idea. The company has been awarded a grant from Innovate UK, the national innovation funding agency. This governmental support accelerates the process and the devices will be available to researchers and businesses in the very near future.

See:

James P. Stratford, Conor L. A. Edwards, Manjari J. Ghanshyam, Dmitry Malyshev, Marco A. Delise, Yoshikatsu Hayashi, Munehiro Asally. Electrically induced bacterial membrane-potential dynamics correspond to cellular proliferation capacity. Proceedings of the National Academy of Sciences, 2019; 201901788 DOI: 10.1073/pnas.1901788116

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Techniques for Improving Drug Solubility

Solubility is one of the most important phenomena in chemistry, pharmaceuticals and any number of other disciplines and industries. In the development of drugs, the ability of a solvent to create a uniform, homogenous system is critical to ensure that drug achieves the desired effect in patients.

A guest post by Megan Ray Nichols

The following list provides a look at some of the more modern and common techniques for improving drug solubility and enhancing the human body's ability to absorb and use them.

1. Reduce Particle Sizes

Reducing the size of the drug particles themselves is one of the most straightforward techniques for improving the final compound's solubility. The smaller the particle, the more surface area is exposed, and the more it can interact with the solvent.

You can apply this principle in several ways. Here are some of the most common:

• Comminution: These processes include grinding, vibrating or crushing the particles until they reach the desired size. This solution is not perfect, however, as the physical agitation may degrade the drug’s effectiveness.
• Spray drying: Food and chemical manufacturing entities have long used spray drying, and it has more recently gained acceptance in the drug industries. Spray drying yields an amorphous material that is many times more soluble and bioavailable than its previous crystalline form.
• Micronization: Modern techniques for micronization involve applying supercritical fluids — such as carbon dioxide — to drugs at high pressures. Supercritical fluids cannot exist in liquid or gas form above certain temperatures. As they pass through a solvent, supercritical fluids cause supersaturation and the homogenous precipitation of the desired particles.

The first two techniques employ physical-mechanical force, while micronization capitalizes on fluid energy. 

2. Hot Melt (Fusion)

The hot melt, or fusion, method is another simple and economical technique. While the term is widely associated with hot melt adhesives, the concept behind such products yields a similar effect when applied to pharmaceutical formulation. Two heated components become more than the sum of their parts.

In this technique, a drug mixture and a water-soluble carrier are both subjected to a heating element until they mix. From there, the mixture formed from the two is cooled rapidly in an ice bath while receiving agitation.

This process yields a solid mass ready to be crushed, sieved, combined with a tableting agent and then formed into tablets. For it to work properly, the drug must be sufficiently miscible — it must be able to mix with another substance in any proportion. When performed correctly, this method improves the cycle time compared to other techniques, including spray drying.

3. Ultra-Rapid Freezing

Ultra-rapid freezing (URF) is one of several techniques based on the principles of cryogenics and lyophilization. It involves applying a thin film of a drug compound to a cryogenic substrate —a frozen surface. This process instantly freezes the drug.

During URF, the drug undergoes lyophilization. This part of the freeze-drying method involves removing water and solvent from the drug compound using a vacuum, changing them from their solid forms directly into their gaseous forms without first becoming a liquid.

The result is nanostructured powdered particles of the desired drug compound, each with improved surface area and high bioavailability.

4. Nanosuspension

Nanosuspension offers efficient delivery of especially hydrophobic and oleophobic drug compounds — drugs that are poorly soluble in both water and oil. Without nanosuspension, the resulting drug would have very low bioavailability and would not achieve the desired medical effect.

The process relies on surfactants. When dissolved in water, surfactants displace air on the surface of powders and particles and allow them to disperse more evenly within a liquid carrier. Surfactants stabilize and homogenize nanosized particles of topical or oral drug compounds within a carrier that they would normally not mix well with.

More than 40% of new chemical entities (NCEs) in drug discovery today are insoluble in water. However, nanosuspension using surfactants allows research and development on these difficult compounds to move forward. 

The Key to Consistency and Effectiveness

This list of available techniques is not exhaustive, and some may be used in conjunction with others. Improving drug solubility is key for reducing the number of dosages required by the patient and ensuring consistent performance of the drug in each case — whether the drug is intended for use in capsules, liquids or immediate- or timed-release formulations.

Digital Transformation of Pharmaceuticals and Healthcare

As with other sectors of the economy, pharmaceuticals and healthcare is undergoing digital transformation and with some companies this is continuing at a rapid pace as companies attempt to mine the sources of data available.

For those involved with the industry, this means an array of new abbreviations, initialism and acronyms to learn. Terms such as: artificial Intelligence, machine learning, internet-of-things (or the ‘industrial’ internet-of-things -IIOT), blockchain, augmented reality, predictive analytics, big data analytics, Industry 4.0 (or Industry X.0), digital twins, and telehealth are becoming part of the modern manufacturing lexicon.

Tim Sandle has written an new article:

Industry 4.0 is the subset of the fourth industrial revolution and it concerns the digital age and the interconnected manufacturing process, plus design of new products and controlling distribution. The route to get there is through digital transformation; and this process has many journeys, ways of thinking and different technologies, which include those centered on smart manufacturing, such as cyber-physical systems, the internet of things, cloud computing, and artificial intelligence. Central to all of this is data and the value that can be drawn from data, either for gaining real-time metrics about operations, production, inventory control, and quality data; to controlling the supply chain (such as through blockchain, which is a digital ledger); and using data for the purposes of predictive analytics.

The reference is:

Sandle, T. (2019): Digital Transformation of Pharmaceuticals and Healthcare, Institute of Validation Technology Blog, published July 2019.

To access, see: http://www.ivtnetwork.com/article/digital-transformation-pharmaceuticals-and-healthcare

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology