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Dry Powder Inhaler Makes Patient Use Easy

10/6/17      Pulmonary drug delivery has the potential to produce maximum therapeutic benefit to patients by directly targeting drugs to the lungs. The dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse range of diseases. Do to the fact that drug delivery from a DPI involves a complex interaction between the device and the patient, the engineering development of this medical technology is key.

DPI systems target the delivery of fine drug particles to the deeper airways in the lungs using a combination of improved drug formulations and enhanced delivery device technologies. These factors contribute to the overall performance of the aerosol system. There are a large range of devices that are currently available, or under development, for clinical use, but a major concern is that the daily patient use of this device may result in under-dosing. That is one of the factors that makes the DoseOne™ DPI is different from the others.

The DoseOne™ is equipped with a simple dose readiness indicator and a dose delivery indicator, and its size and ease of use (relying on patient inhalation rather than propellant technologies) make it well suited to environments where local health services are sub-optimal. As a single dose device it minimizes the dose-to-dose consistency risk and also negates the requirement for priming needed by many devices.

In addition, as DoseOne™ is a single use disposable device, a new device is used for each dose, eliminating the frequent problem of powder caking and flaking which can affect dose volumes in multi-dose devices. Also, as a single use device, the issue of, and problems associated with, dose counting — which preoccupies the FDA and other health organizations around the world — is made redundant. In its current state, DoseOne™ contains a simple dose readiness indicator as well as a dose delivery indicator in the form of a viewing window, therefore promoting patient compliance by confirming the dose is ready and has been completely administered.
To learn more about DoseOne™ and how to partner up with us, please visit the website: www.Dose-one.com and contact Donna Bibber at 774-230-3459 with any questions you may have.

Tiny Medical Device Validation – Designing for Success

9/20/17     This is a blog from isomicro.com:

VALIDATION

Picture this – your medical device is designed and you’re ready to validate the tiniest component – the technology piece that enables your intellectual property. You dive in head first, knowing your part has +/- 5 micron tolerances on a plastic part. You start like any engineer would start – with a solid stack-up tolerance plan and <20% gage R&R – you should be fine, right?

Consider this general micro molding rule of thumb – BEFORE you even design the injection mold. If you work backwards with the numbers, you’ll have ~0.0004” total tolerance

Total   10 microns = (0.000397”)

Tooling = 20% of 10 microns = 0.00008” (wow, really? This is difficult to do but SO critical to hitting the final Cpk.

Cpk of 1.33 or better on this tolerance means you need ~20% of the tolerance left (and be tightly controlled) to hit your CPK.  The error breakdown generally speaking is:

Tooling 20%
Gage R&R 20%
Molding process 20%
Material lot to lot variation 10% – melt flow, venting
In the bank- 10% for some unforeseen couple of microns

Starting with the tooling (it’s almost always about the tooling), anything we can do to reduce the 20% of steel tolerance in a critical tolerance will increase the numerical dance of success as explained above. Achieving steel tolerances of +/- 0.0002” is fairly straight forward in the precision mold-making industry, however achieving 20% of this is not straight-forward and requires some good research to make sure you have one that can. Selecting the right tooling supplier is the #1 absolute critical contributor to overall micro molding product success.

It’s equally important to understand the gage R&R error in the still measurement as well as the end plastic component. Creating the steel may require EDM, milling, wire EDM, or grinding. Validating steel or pieces of steel that make up a critical feature requires that the metrology equipment is capable of one more resolution higher than the tolerance. For example 20% of 0.000397” = < 0.00008” which requires 0.00001” or better in measurement capability in both steel and plastic. If the tooling supplier doesn’t have this capability, there’s no way to quantify the very start of the process to creating a micro molded part. If the tooling supplier has this capability, you are off to a great start in achieving the final goal of CPK 1.33 or better – a necessary requirement for many medical and drug delivery devices.

Micro Expert to speak at upcoming conference

9/8/17     Medtech notable Donna Bibber, Vice President of Sales and Marketing for Isometric Micro Molding Inc. and President at Micro Engineering Solutions Inc., will be the keynote speaker at the medical extrusion conference. A University of Massachusetts-Lowell graduate with 25 years of experience in micro manufacturing, Bibber has published technical papers on micro and ultra-precision manufacturing topics worldwide. She was named one of 100 notable people in the medical device industry by sister brand MD+DI in 2008. Bibber was president of Micro Engineering Solutions at the time.

The conference, scheduled for Nov. 7, 2017, in St. Louis Park, MN, will address a range of technical issues related to medical extrusion, including:
• Manufacturing micro-medical devices using precision over-molded tubing;
• the role of pellet size in process stability of PA-12 micro-extrusion;
• medical tubing die and process optimization;
• jacketing of discrete guidewire lengths and automation of secondary processes;
• vacuum sizing small-bore tubing; and
• processing semi-crystalline materials

Speakers include Anthony Walder, Global Technology Manager at Lubrizol Corp.; John Perdikoulias, PhD, President of Compuplast Canada Inc.; Jonathan Jurgaitis, Senior Extrusion Engineer at Apollo Medical Extrusion; and Dave Czarnick, a tooling expert with 25 years of experience who holds five extrusion-related patents.
This conference is designed for individuals interested in extruding medical tubing and performing secondary operations such as braiding, over molding, surface treatment and laser drilling for catheters and delivery systems.

The Fall Spotlight Medical Extrusion & Secondary Operations Conference is hosted by Graham Engineering brand American Kuhne.
For more information and to register to attend, click here.

Micro Motor Drug Delivery

8/31/17     Researchers at the University of California San Diego have created micromotors to treat bacterial infections in the stomach. These micro sized vehicles (half the width of a human hair) swim rapidly through the stomach to release antibiotics at a desired pH. This micromotor-enabled delivery approach is a promising new method for treating stomach and gastrointestinal tract diseases with acid-sensitive drugs.

When people take orally administered drugs such as antibiotics and protein-based pharmaceuticals, gastric acid in the stomach can wreck havoc with them. Because of this, drugs used to treat bacterial infections, ulcers and other diseases in the stomach are normally taken with additional substances, called proton pump inhibitors, to suppress gastric acid production. The problem arises when taken over longer periods or in high doses, proton pump inhibitors can cause adverse side effects including headaches, diarrhea and fatigue. In more serious cases, they can cause anxiety or depression. To conquer this, the micromotors have a built-in mechanism to neutralize gastric acid and effectively deliver their drug payloads in the stomach, without the use of proton pump inhibitors.

Each micromotor consists of a spherical magnesium core coated with a protective layer of titanium dioxide, followed by a layer of the antibiotic clarithromycin, and an outer layer of a positively-charged polymer called chitosan that enables the motors to stick to the stomach wall. This binding is enhanced by the propulsion of the micromotors, which is fueled by the stomach’s own acid. The magnesium cores react with gastric acid, generating a stream of hydrogen microbubbles that propel the motors around inside the stomach. This reaction temporarily reduces the amount of acid in the stomach, increasing the pH level enough to allow the micromotors to release the drug and perform treatment. The normal stomach pH is restored within 24 hours.

Clinical trials on mice with Helicobacter pylori infections were done. The micromotors, loaded with clarithromycin, were administered orally once a day for five consecutive days. Afterwards, researchers evaluated the bacterial count in each mouse stomach and found that treatment with the micromotors was slightly more effective than when the same dose of antibiotic was given in combination with proton pump inhibitors.

So what happens to these micromotors after they deliver their drug? Since they are made of mostly biodegradable materials, the magnesium cores and polymer layers are dissolved by gastric acid without producing harmful residues.

Our Dry Powder Inhaler is ready for your application

8/16/17     DoseOne, LLC holds multiple patents and prepared to partner the most innovative DPIs available today, the DoseOne™ Single Dose Powder Inhaler.

Below is an article in FiercePharma about the dry powder inhaler we have blogged about in the past.

Development of the DoseOne™ single dose powder inhaler (US Patents #7,832,399 B2 and #8,360,057 B2) required a multi-disciplinary team approach, as any such drug delivery device needs to combine not just design skills, but also software and mechanical engineering capabilities, and expertise in analytical science and industrialization. From concept to creation, the DoseOne™ device was designed to be sympathetic to the requirements for mass manufacture and regulatory compliance.

The two patents associated with the DoseOne™ single dose powder inhaler cover the unique dosing mechanism of the device, and the ability to use the technology for dual-drug delivery. The DoseOne™ inhaler contains multiple, segregated air pathways, which keeps powder hold-up to a minimum, and makes device optimization for powder properties considerably easier. Using this technology which drives the DoseOne™ inhaler, designs have been developed and patented for dual drug delivery, the device allowing for simultaneous release of two different and separately contained drugs.

From a manufacturability point of view, the key advantage of the DoseOne™ is its simplicity and intuitive use (one motion and complete). Through the expeditious use of design and micro manufacturing expertise, DoseOne™ is an easy to manufacture and assemble 3-component device. The simplicity is of great importance as an inexpensive drug delivery option, costing $0.16 per device at full volume. The ultra-precise nature of the design and components also ensures that the device is small, which makes it easy to carry and package for mass drug distribution.

The inherent characteristics, size, and nature of the drug delivery technology make the DoseOne™ inhaler hugely advantageous for numerous end use applications. One obvious area of interest is in third world treatments of pandemics and epidemics, where there is an enormous emphasis on safety of drug delivery, simplicity of drug delivery, and ways to show compliance with dose administered. The DoseOne™ is equipped with a simple dose readiness indicator and a dose delivery indicator, and its size and ease of use (relying on patient inhalation rather than propellant technologies) make it well suited to environments where local health services are sub-optimal. In addition, for mass drug administration the low unit cost of the device is obviously hugely significant.

The DoseOne™ is extremely easy to validate, and is ideal for drop-shipping with all this implies in reduction of total inventory management and shipping costs, which can reduce the end use cost of the device.

The simplicity of the design also makes it easy to revise to accommodate specific formulations. Of especial importance, however, is the ability using the DoseOne™ inhaler to simultaneously pierce capsules containing different drugs, meaning that the drugs mix within the body, so there is no necessity to address drug interaction issues as would be the case if the drugs were mixed in one capsule.

DoseOne™ is a perfect example of what can be achieved if an innate understanding of micro manufacturing design and manufacturing is combined with an understanding of the regulatory environment that exists around drug delivery devices these days, and a realization of the potential for innovative solutions that cater for mass “self” administration of drugs in a cost-effective and safe way.

The Market for DPIs.
Powder inhalers deliver drugs in the form of dry powder directly to the lungs, and are typically used in the treatment of respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD), asthma, and emphysema. However, due to many of their innate characteristics and advantages as a drug delivery mechanism, there is burgeoning interest around the use of dry powder inhalers (DPIs) in the pharmaceutical and medical device sectors.
In many ways, DPIs have become more prevalent as they have been tailored for markets previously catered for by Metered Dose Inhalers (MDIs), which many patients find difficult to use, which rely on propellants that have come under more and more legislative scrutiny, and — from the device manufacturers and pharmaceutical company’s perspective — are often expensive to make. It is generally agreed that DPIs are easier to use as they simply rely on patient inspiration to deliver the drug, and are less likely to lead to side-effects such as irritation of the airways.

As with all families of drug delivery devices, the balance for drug companies is between affordability and functionality. Unit cost per device is obviously critical, as is the ability for the drug to be delivered in the correct dose, and for there to be minimum drug wastage.

The DoseOne™ Solution
DoseOne™ is a single-use disposable DPI, and as such overcomes many of the problems associated with multi-use DPIs and MDIs. As a single dose device, for example, it minimizes dose-to-dose consistency risk, and also negates the requirement for priming needed by many devices, with all this implies in respect of drug wastage.

In addition, as DoseOne™ is a single use disposable device — and therefore a new device is used for each dose — it eliminates the frequent problem of powder caking and flaking which can affect dose volumes in multi-dose devices.

Also, as a single use device, the issue of, and problems associated with, dose counting — which preoccupies the FDA and other health organizations around the world — is made redundant. In its current state, DoseOne™ contains a simple dose readiness indicator as well as a dose delivery indicator in the form of a viewing window, therefore promoting patient compliance by confirming the dose is ready and has been completely administered.

As such, DoseOne™ satisfies the regulatory demands previously only achieved by complicated and expensive designs. So for any pharma or device manufacturer looking to locate a novel, cost-effective, and efficient drug delivery option please call or email Donna Bibber at dbibber@doseone.com to discuss potential partnerships.

The Merging of Medical Device and Pharmaceutical Industries

7/27/17     As product technology advances and the general demand for healthcare expands, the industry line between medical device manufacturers and pharmaceutical companies are being blurred as innovative products continue to emerge. Manufacturers are exploring new technologies that adhere to better patient compliance, improve product safety and utilize unique drug delivery methods.

These new technologies include:
–  Small adhesive patches that are encapsulated and swallowed. Once in the body they dissolve and stick to the wall of the intestine to deliver time released    medication
– Implantable devices that automatically run tests and dose medications
– Transdermal patches that are embedded with micro sized needles that deliver medication over a period of time

As technology advances and healthcare treatments become more complex, the pharmaceutical and medical device industries will continue to merge their technologies and expertise to deliver patient solutions that combine both pharmaceuticals and medical devices into one simple and convenient product. Currently about half of all manufacturers in both industries have turned to contract services to meet demand as products become more intertwined.

As this newly meshed relationship forms there are many concerns and factors that both industries need to keep in mind, with the top two being:
1. Regulations: Government regulation requires manufacturers to adapt their processes to meet changing production demands of speed, flexibility, and safety while continuing to comply with regulations. Complying with these regulations usually requires a large investment in machinery and software systems, with two out of three companies reporting that they will be spending more on capital equipment in the next two years. Smaller manufacturers are having a hard time with this large expenditure burden, so they are turning to OEMs to help with regulation compliance strategies by adapting their machines to meet data acquisition and storage requirements for marking and tracking products which includes coding and vision inspection systems.
2. High Demand: In addition to complying with numerous regulations, pharmaceutical and medical device manufacturers also face the challenge of increasing consumer demand. This demand is fueled by increased insurance coverage rates and improved healthcare availability. To meet this demand, manufacturers have to produce products at a faster rate, while adhering to stringent regulations. As a result, many manufacturers have turned to smaller batch runs with greater product diversity and more frequent changeovers, requiring machines that are both fast and versatile. OEMs can be a valuable partner in adjusting to process changes by providing manufacturers with innovative, flexible machine builds that are designed to integrate seamlessly into production lines and software systems.

Manufacturers Need a Partner – As pharmaceutical and medical device companies strive to keep up with market demand, they will search for trusted partners to help them comply with the maze of complex regulations. Manufacturers will also need help with the process of implementing new technology, especially automation and data management solutions, which will play a crucial role in a manufacturer’s ability to operate efficiently in a growing market. OEMs and technology suppliers are perfectly situated to offer their experience and expertise to manufacturers as an invaluable tool in resolving future challenges; expertise in automation, integration services, and regulation compliance are key. OEMs and technology suppliers can form stronger relationships by working collaboratively to address a manufacturer’s unique needs on an individual level, in order to achieve a mutually beneficial partnership.

Removing the “patient factor” from glaucoma treatment

7/20/17     Over 3 million Americans suffer with glaucoma and 75% of them administer their own drug treatment incorrectly. These “patient factors” include not being able to see clearly enough to pick up the right medication to use, the inability to successfully put droplets into the eye, and simple forgetfulness.
Sustained delivery devices that take glaucoma therapy out of patients’ hands may be the answer to the many issues related to adherence, with significant benefits for patients and physicians. These technologies are broken into 3 general categories: injectable sustained-release formulations, drug-eluting rings and contact lenses, and punctal plug reservoirs.

glaucoma ring
Drug-eluting rings are currently in clinical trial right now. They are made of a silicone polymer and can house most any drug combination. The ring is put under the eye lid and slowly excretes drug delivery for up to 6 months. This alleviates the patient having to remember to take their medicine. An issue researchers are trying to overcome with rings is they can fall out without the patient being aware of it happening, making it virtually unknown how much of the drug the patient actually received. Once this hurdle is overcome the next obstacle is to figure out the timing of introducing this treatment to a patient. Timing can be a critical factor in the successful treatment of glaucoma. Once the clinical trials are completed and the logistics figured out, drug-eluting rings will most likely play a significant role in glaucoma treatment.

Micro Molder vs. Conventional Molder

7 reasons you need a Micro Molder vs. Conventional Molder

  1. Shot size is less than 30% of barrel capacity
  2. Your tooling source thinks it’s doable but “hasn’t made a mold quite that small before”
  3. Optimized runner systems in comparison to longer runner systems
  4. Your molding source doesn’t have metrology equipment with high resolution
  5. Highly complex detail is achievable with a micro molder
  6. Low tolerance tooling and molding processes
  7. Minimal material waste = money savings

Wearable Micro Component Health Sensors

7/6/17     Wearable sensors combine computers with our bodies. Companies like Google and Apple are focusing on self-health monitoring. We have already been introduced to things like Fitbit which offer wearable fitness trackers that record our footsteps and heart rate. In the near future these health sensors will evolve into items more complex yet smaller in size. The thought of wearing a bulky bracelet to monitor your heart rate will be replaced with adhesive sensors similar to a sticker. They can be worn on the skin and the material makes them bendable and stretchable, like this prototype from MC10 which senses heart rate and other vital signs.

micro component sensor

These breathable, bendable, stretchable devices are, in itself, a hurdle to overcome when designing them. They need to be able to do all of the bending and stretching while keeping all of the micro components inside that make them work from breaking or malfunctioning. Imagine a tiny battery or sensitive sensor being able to move with our skin and nothing inside the component breaks. This is where state of the art technology and novel micro-component expertise come in. Without them, these new technologies wouldn’t exist.

Besides the numerous health benefits and ease of use, wearable health sensors allow patient’s health to be tracked over time, efficiently and without frequent, costly follow up visits to the doctor. This could have a positive impact on healthcare costs. The future of wearable health sensors could help us manage chronic illnesses and chronic pain; they could be an early detection warning of an on-coming illness or episode like a seizure; and they could send daily accurate information to our doctors informing them of things we may not even realize is going on within our bodies.

Seeking Partner for Single Dose Powder Inhaler

6/29/17     Introducing DoseOne™, a single dose powder inhaler that is already prototyped, tested, recently benchmarked, and ready for pilot production and a partner to move it forward.  The design is SO simple it’s something that makes you say, “Darn, I wish I thought of that, it’s so simple!”

Simple means inexpensive (~$0.30 USD in Full Volume) and fast to market and can be tested in pilot production immediately because it is already designed, molded, and ready for slight modifications to fit a particular size molecule.

 

 

 

 

 

 

 

 

 

Dose-One Patent #7,832,399

 

DoseOne™ is a single use disposable dry powder inhaler that is:

–       Vaccine-ready

–       Easy to Carry & package for epidemic/pandemic necessity

–       Fills a unique niche in the dry powder inhaler market

Achieves new demanding regulatory requirements previously only achievable using complicated device designs such as:

  • Dose counting
  • Powder holdup
  • Dose readiness indication
  • Dose completion / user feedback

DoseOne™ is extremely easy to use and requires minimal training

–       The device, as currently designed, requires three steps to use

  • Removal from over-pack
  • Actuation
  • Inspiration

–       Actuation is a simple compressive snap

–       As a result of it’s simple operation, DoseOne™ has an excellent application in the delivery of drugs (such as vaccinations) to third-world countries

 

 

 

 

DoseOne™ is currently a three component inhaler with:

  • All three components are highly manufacturable.
  • Long term material selection which can be determined by the customer as a function of drug chemistry as the device design requires very few material constraints.
  • Current performance data which utilized pharmaceutical grade/USP Class VI resins.

Regulatory Advantages:

  • DoseOne™ is a single dose device, minimizing dose-to-dose consistency risk.
  • No device priming.  Many inhalation systems require a prime of the device of a number of shot before use.
  • DoseOne™ uses a new device for each dose and thus eliminates the issue of powder “caking and flaking” (deposition during inspiration adding to dose volumes of later doses).
  • No dose counting!  The FDA and other world health organization strongly recommend the use of dose counters or indicators to increase patient compliance. DoseOne™ is one device, one use, and disposable.
  • The current device design contains a very simple dose readiness indicator as well as dose delivery indicator.  This comes in the form of a viewing window to allow the user confirmation that the dose is ready, and that the dose has been delivered.

Development Status

  • DoseOne has constructed tools for the current DoseOne™designs (Size #2 and Size #4)
  • Size #0 and Size #1 design embodiments are tooling kick-off ready.  Feasibility, optimization, and DFM details are complete.
  • Current single cavity tools are Phase I clinical ready
  • Devices are currently in a molded and fully functional state
  • US Patents are granted

–       US PAT #7,832,399

Partnering Expectations/Goals for DoseOne, LLC:

–       Partner with successful formulations development/OEM companies interested in providing patients with effective treatment

–       Develop mutually beneficial milestone based license arrangements which results in an expeditious time to market

–       Continuously adjust and improve device performance as new formulations become available

–       Supply the marketplace with a unique device partnered with an effective drug

 

Interested? Contact Donna Bibber at 774-230-3459 or Donna@MicroEngineeringSolutions.com.