EPM Oral Solid Dosage Supplement 2018

| ORAL SOLID DOSAGE SUPPLEMENT

INSPECTING ON THE EDGE Natoli Engineering outlines the steps needed to reduce and prevent tooling tip wear

The Reality of Continuous Pharmaceutical Manufacturing User experiences and the current status of going conti to be addressed during a 3-day event near Newcastle, UK

Taking place on 26–28 March 2019, GEA, Siemens and Perceptive Engineering will host an inaugural 3-day conference to examine the fact and fiction of continuous manufacturing (CM) in the pharmaceutical industry.

With an expected attendance of 80–120 delegates, this must-attend event will focus on the real-life experiences of existing users of CM technology in the development and manufacture of oral solid dosage (OSD) forms. #TheContiTruth #PharmaContiFacts Contact gea.com/contact for more information and learn how GEA is #MakingScienceWork

WWW.EPMMAGAZINE.COM

Contents ORAL SOLID DOSE SUPPLEMENT REGULARS 3: EDITOR’S DESK

Coming full circle

T

o say that the pharmaceutical market is vast would be an understatement. In its current climate, the market is evolving through continuous manufacturing, big data and industry 4.0 whilst issues including Brexit and the opioid crisis in the US place even more pressure on both manufacturers and most importantly patients.

A recent article in the CPhI Annual Industry Report1 highlighted the steps taken during the production of a pharmaceutical dosage, simplifying it to a summation of processes that exist to produce the required end-product.

Take this issue for instance, which covers everything ranging from a case study involving the latest coating technology, how sprinkle formulation is putting the focus back on patients and how manufacturers can avoid tip wear during tooling.

Each topic represents a specific look at the oral solid dosage market but when combined, should provide a rounded appreciation of the steps taken to get a drug to market. Whilst none of the topics can ever be deemed ‘simple’, each plays an important role in the formulation of a drug, each one as essential as the last.

That’s why here at EPM, our 360 Series takes a holistic approach to pharmaceutical manufacturing, incorporating every aspect of the sector so our readers get an uncompromising view of specific topics.

There’s plenty to dive into and with oral solid dosage forms remaining dominant within the market2, it’s fair to say that we can expect plenty more exciting content regarding the sector in the future.

Re-introducing European Pharmaceutical Manufacturer’s 360 Series and how it takes a holistic view of the industry.

5: ANOTHER DOSE A round-up of the latest oral solid dosage news including stories on the market’s predicted growth, expansions, grants and a cannabis capsule to treat chronic pain.

FEATURES 8: COVER STORY Natoli outlines how tip wear can lead to a range of issues during tablet design. This feature covers the steps needed to avoid wear in tooling.

10: FORMULATION Find out how the latest sprinkle formulation technology is helping manufacturers put the focus back on the patient in medicine.

13: CASE STUDY This case study from IMA Group assesses the latest coating technology during the pellet coating process.

REFERENCES 1: https://www.cphi.com/europe/visit/news-and-updates/annual-industry-report-2018-final 2: https://www.lanews.org/new-report-oral-solid-dosage-pharmaceutical-formulation-market-analysis-2017-2027/

HEAD OFFICE Carlton House, Sandpiper Way, Chester Business Park, Chester, CH4 9QE. Tel. +44 (0)1244 680222 Fax. +44 (0)1244 671074 Web: www.epmmagazine.com

EDITORIAL editor reece armstrong reece.armstrong@rapidnews.com

PRODUCTION haed of studio and production sam hamlyn

deputy group editor dave gray david.gray@rapidnews.com

design robert wood

head of content, life sciences lu rahman, lu.rahman@rapidnews.com publisher duncan wood

3

ADVERTISING robert anderton tel: +44 (0)1244 952359, robert.anderton@rapidnews.com head of media sales, plastics & life sciences lisa montgomery lisa.montgomery@rapidnews.com

development

your molecule has so much potential. our passion for development will help unlock it.

As the #1 global leader in drug development, Catalent's comprehensive capabilities, robust scientific approach, and broadest selection of enabling technologies can help you overcome the toughest development challenges. With the acquisition of Juniper Pharma Services in Nottingham, UK, Catalent’s multi-site network provides innovators with a more complete and integrated solution to accelerate development from clinical to commercial supply.

comprehensive development offerings: candidate selection & dmpk modeling solid state & preformulation preclinical & clinical formulation bioavailability enhancement clinical cgmp manufacturing comprehensive analytical solutions clinical supply services

expanded optiform‰ solution suite One accelerated, flexible, and data-driven solution combines all analytics, services and materials your molecule needs from candidate selection into Phase 1.

Catalent. More products. Better treatments. Reliably supplied.™ us + 1 888 SOLUTION (765-8846) eu 00800 8855 6178 catalent.com/optiform ˝ 2018 Catalent Pharma Solutions. All rights reserved.

OSD SUPPLEMENT

ANOTHER DOSE

Intract Pharma receives £1.4m grant to develop antibodies Drug delivery developer Intract Pharma has been awarded a £1.4 million grant

by Innovate UK to develop a scalable manufacturing process for novel oral antibody products.

The company will develop a manufacturing process for its Soteria technology which can then be scaled in a commercially viable manner. Soteria is able to transform painful injectable therapies into safe, oral formulations. In particular, the technology targets the antibody at the site of disease in the gut to improve its therapeutic effect whilst minimising risks of systemic toxicity.

The programme will be conducted by a consortium led by Intract, including the Centre for Process Innovation (CPI), Pharmidex and Quay Pharma.

Intract’s CEO, Bill Lindsay, said: “Intract has invested significant resource in developing Soteria at laboratory scale – Innovate UK funding is critical at this point to resolve the issues involved in large-scale GMP manufacture of biologic drugs.”

Intract’s work on developing a manufacturing process for antibody products, which has great potential to improve patients’ treatment. Our position within the consortium also allows us to demonstrate the breadth of capabilities we have here at CPI and how we have been able to bring them to bear to offer our support.”

Dr Graeme Cruickshank, CPI director of formulation, said: “We are delighted to be supporting

Intract will use the monoclonal antibody, infliximab, as a model biologic for the programme, potentially developing an oral product utilising the knowledge gained during the study.

LONZA EXPANDS SERVICES FOR PARENTERAL DOSAGE

Lonza has expanded its footprint for parenteral dosage form development by investing in its Drug Product Services (DPS) site, the company has announced.

The expansion comes in response to market demand, with the company now increasing both the capability and capacity of DPS at its Stücki Science Park in Basel, Switzerland.

Lonza is also nearing the end of recruiting phase that will extend the number of DPS employees to 125 staff.

The expanded offering includes new capabilities for a range of services, including, clinical administration and compatibility testing; lyophilisation cycle and process development; device functionality testing and lifecycle management line extension.

5

Lonza DPS opened two years ago and has since developed solutions for 88 molecules. The site complements the company’s service in biologics with end-to-end capabilities.

Karen Fallen, senior vice president and head of clinical development and manufacturing, Lonza Pharma & Biotech, said: “Including drug product services in the portfolio provides our customers with a single supplier for their clinical outsourcing requirements.

DPS customers recognise our commitment to their challenges.

We have built an experienced team with the ability to solve problems based on scientific, industry and regulatory know-how.”

WWW.EPMMAGAZINE.COM

PCI PHARMA TO MANUFACTURE AUSCANN’S FIRST MEDICINAL CANNABIS PRODUCT FOR CHRONIC PAIN Medical cannabis company AusCann has chosen PCI Pharma to manufacture and release its first product designed to help treat chronic pain.

PCI Pharma will produce and release AusCann’s solid hard shell capsules for the treatment of chronic pain. The capsules, scheduled to be released in 2019, are intended to help the estimated 1.9 million

Australians who suffer from chronic pain. The product line is also set to be made available internationally and for clinical studies.

Elaine Darby, managing director of AusCann, said: “AusCann elected to work with PCI Pharma due to their significant experience in providing manufacturing services of solid dose potent products to high standards of safety and quality. This allows

AusCann to bring its first hard shell capsules into the chronic pain market as quickly as possible, while continuing to focus on the development of our second generation cannabinoid pharmaceutical products.”

By 2027, the oral solid dosage (OSD) market is set to be worth $926 billion according to research group Future Market Insights.

High hopes for oral solid dosage market

The group’s latest report focusses on the OSD market, stating that from 2017 – 2027 the market will see a CAGR of 6.5%.

The market’s anticipated growth isn’t entirely surprising, especially when you consider that OSD forms are the most commonly used pharmaceuticals to treat a variety of conditions and diseases.

Recently there has been a huge boost in the Asian Pacific Excluding Japan (APEJ) market due to consumers in countries such as India, China and Korea.

The adoption of related lifestyles across populations in India and China is causing a rise in western lifestyle diseases such as diabetes, cancer and obesity,

6

leading to an uptake in innovative drug treatments.

New global opportunities are being made by generic manufacturers producing modified versions of approved off patent small-molecule drugs.

These so called ‘super-generics’ offer a therapeutic advantage, distinguishing them from regular generic drugs. The report gives the example of the once-a day Ciprofloxacin tablet, developed

by India-based manufacturer, Ranbaxy Laboratories, who licensed the ‘super-generic’ to Bayer.

The OSD market however is being hindered by the growing research on biologics molecules, which hold a dominance in treating oncology, the report states. More so, funding into biologics by governments are now starting to have a negative impact on the OSD market.

7

WWW.EPMMAGAZINE.COM

Inspecting on the Edge Tip wear can lead to a host of issues for tablet design. Here, Bill Turner, technical service manager, tooling and tablets, and Kevin Queensen, technical service support tooling and tablets, Natoli Engineering, discuss the steps needed to avoid wear in tooling.

W

ear to the edges of punch tips is overlooked in many tooling inspection procedures. Many factors can cause tip wear, including poor tablet and tool design, granulation characteristics, and improper steel selection for the application.

While inspection technicians typically The design of pay attention to the the tablet plays punch cup face, tablet defects are an integral in fact more often role in the related to punch tip and outer edge functionality land wear.

and longevity of tooling.

Figure: 1

coat and can lead to loose particles adhering to the coated tablet surface.

Understanding the most frequent causes of punch tip edge wear is crucial to minimising defects and downtime.

While proper inspection can help prevent common tabletting defects, punch tip inspection often only checks the size of the tip by measuring it with a micrometer or calipers. Wear to the very edge of the punch tip is relatively small, is undetectable using traditional measuring equipment and techniques, and may not be easily observed by unassisted visual inspection.

COMMON CAUSES OF PUNCH TIP WEAR Formulation/Granulation Characteristics Abrasion due to granulation can cause tip wear, most commonly in the nutraceutical industry. Nutraceuticals are usually composed of different vitamins and minerals, most of which are quite abrasive. Pharma products with a higher percentage of active pharmaceutical ingredient (API) typically require higher compression forces, which may accelerate tip wear.

Punch tip edge wear can lead to problems like raised edges on the final compressed tablet, commonly referred to as “flashing� (Figure 1).

In turn, tablet flashing can cause many other issues after the compression event. When tablets are subjected to de-dusting, the flashed edges may break off, leaving rough, poorly defined edges. Tablets with flashing can be difficult to film

Abrasive ingredients also erode the land and the outer edge of the punch tip. Once wear occurs to the edge of the punch tip, particles will become trapped in the increased gap between the tip edge and die wall. As the punch moves vertically, the abrasive particles are ground between the tip and die wall, accelerating the wear to both tool components and the overall wear process.

8

Particle size also can affect tip wear.

Small particles, known as fines, can sift into the gap between the punch tip and die bore (Figure 2). Fines, combined with the cyclic motion of the punches, can cause wear on the outer edges of punch tips. While often there is little or no choice as to the components of a formulation, controlling particle size and tipto-die-bore clearance can reduce unnecessary tip wear and extend tool life.

Figure: 2

TABLET DESIGN The design of the tablet plays an integral role in the functionality and longevity of tooling. If the cup is excessively deep or if the concavity of the cup is steep near the edge with nearly vertical surfaces, it will be more susceptible to abrasion. This type of cup design is not as robust as a standard cup and will require more land than its counterpart.

Steps to strengthen the edge of the punch cup include reducing the slope of the cup and introducing an appropriate amount of land into the tablet design.

Land gets a bad reputation as many believe additional land may cause

OSD SUPPLEMENT

edge chipping and difficulty with film coating. Whilst tool vendors know the value of land and may incorporate it into design, many are forced to use a minimal land width of around 5% cup depth. Knowledgeable tablet designers believe that land width should be closer to 10% – and occasionally up to 20-25% – especially for difficult-to-compress tablets that require high force. Having sufficient land in your tablet design adds strength and wear resistance, both on the inside of the cup and on the outside of the tip, while creating a more robust tablet and enhancing tablet stability.

REDUCING AND PREVENTING TIP WEAR Tool Design (Configuration) Refinements are made to the basic tool design to improve performance and extend life. One of the most commonly used tool options is tapered dies, which can resolve capping and laminating issues and make it easier to eject the tablet from the die. Tapered dies can also help offset mild turret misalignment by guiding the upper tip into the bore, bypassing the potential contact with the lead-in chamfer.

COVER STORY

yet still allows them to support the compression forces needed for the high-stress, high-cycle loading conditions of tablet compression.

INSPECTING FOR TIP EDGE WEAR Punch tip edge wear can come from a variety of circumstances and may cause significant quality-related issues. It is important to understand and know how to identify the most common causes of this type of wear. Punch tip edge wear can be difficult to detect because traditional methods of inspection are ineffective.

Fortunately, the use of a horizontal optical comparator (Figure 3) makes inspection easy – and fast. Avoiding punch tip edge wear when possible, and quickly identifying when it does occur, will provide great benefits to the quality of your tablets and to your production operation.

Selecting the proper steel type can help reduce tip wear for abrasive granulates. For very abrasive products, punches can be produced from premium wear-resistant PM (particle metallurgy)-grade steels. As the hardness increases on premium tool steels so does the abrasive wear resistance, but it must be noted that the impact toughness decreases somewhat. Some steels are required to be cryogenically tempered (-184°C, -300°F) to increase wear resistance.

If your vendor does not offer this tempering process, either the steel type or your tooling vendor should be reconsidered. The combination of each steel’s unique chemistry and the related heat treatment process allows different types to attain their unique mechanical properties. This makes them ideal for the wear resistance needed for abrasive formulations

9

Figure: 3

Screen of Natoli Optical Comparator

WWW.EPMMAGAZINE.COM

Teaching old tech new tricks Sven Stegemann, director of pharmaceutical business development, Lonza Pharma & Biotech, discusses how using sprinkle formulation technology helps manufacturers focus on the patient in medicine development.

I

n the past 20 years, advancements such as human genome sequencing and drug products like Herceptin which target gene-derived breast cancer have opened up a new scientific horizon to understand diseases’ root causes and to identify clinical targets and their respective treatments.

Since these advancements, there have been an increasing number of personalised medicines enabled by diagnostic tools that can identify which patients will benefit from treatments and how they can best be administered. These developments are moving the pharmaceutical industry from its traditional manufacturing approach toward more customisation up to the point of manufacturing for a single patient (CAR-T cell therapy).

Along with the increasing personalisation of therapies, patients are being recognised as an important factor in achieving therapeutic outcomes.

Regulators in Europe1 and the in the United States2, 3 have started to consider and request direct patient involvement in drug development in order to better evaluate risk-to-benefit for patients by capturing their personal experiences with specific therapies. This means the mode of administration and the product usability will become major endpoints for the benefit-risk evaluation and product approval.

The personalisation as well as patient focus in drug development and manufacturing affects all stakeholders along the product lifecycle value chain, ranging from early development stages through to manufacturing and distribution. One of the major challenges of personalised and patient-centric product development is the high degree of flexibility required to accommodate the combination of two or three different drugs at individual dose strengths, as well as oral administration to patients with swallowing impairments. For example, the recent regulatory requirements to develop paediatric formulations led to substantial research into the appropriate formulation and drug product approaches that are suitable from an industrial manufacturing standpoint. The research concluded that mini-tablets and multiparticulates provide the high degree of dosing flexibility required for therapeutic dosing based on age or body weight. Moreover, clinical studies provided evidence of the acceptability and swallowability of mini-tablets and multiparticulates even in very young patients4,5.

These studies have reemphasised the concept of using multiparticulates as an oral delivery form for patients with immature swallowing responses, such as paediatric patients, as well as patients with impaired swallowing functions like geriatric patients, multimorbid patients or patients with specific diseases like M. Parkinson. To ensure safe swallowing, the multiparticulates are administered within a small portion of patient-preferred foods or beverages, also known as “sprinkle administration�.

Traditionally, multiparticulates suitable and labelled to be used in sprinkle administration are filled into two-piece hard capsules that could be swallowed as a whole or opened manually. While many products have been brought to market for sprinkle administration, the major limitation is the manual opening of standard capsules due to the very tight closing seal. The alternative use of sachets or stick packs for sprinkle products faced similar issues of opening and multiparticulate release, resulting in the limited success of the sprinkle use of multiparticulates.

The value for patients to receive a personalised treatment in an appropriate formulation and dosage form led to interest from researchers to improve the sprinkle formulation approach with suitable delivery multiparticulate technologies. To accompany these initiatives, the FDA drafted

10

OSD SUPPLEMENT

FORMULATION

guidelines for the development of sprinkle formulation and their administration with soft foods and beverages to support the industrial development of sprinkle products6. Furthermore, these guidelines take into consideration the fact that personalised medicine administration would also include personal preferences in soft foods and beverages, which increases the acceptance and palatability of the medicine.

Demonstrating that the multiparticulates can be used with a variety of soft foods and beverages safely provides the highest level of flexibility and personal preferences in oral administration to the patient.

With the increasing interest in developing sprinkle products, industrial partners to pharmaceutical companies have collaborated to solve for the challenges of effective taste-masking and dosage forms of multiparticulates. For example, Melt-Spray-Congeal (MSC) technology, which uses lipid excipients that are solid at room temperature, was developed to mask taste. The drug is incorporated into the hot melt of a lipid excipient that is atomised by centrifugal forces into microspheres of 150 - 350 Âľm particle size. These microspheres have been applied to several drugs and are proven to cover the taste by themselves or after respective taste-masking coating has been applied. The drug release from MSC microspheres can be modified based on the selection of lipids as well as processing conditions.

To overcome the challenge of dosage forms for multiparticulates in sprinkle use, capsule suppliers have investigated different options to facilitate the manual opening of the two-piece capsule by different patient populations. For example, after defining the required specifications for a capsule that includes non-separation of cap and body during transport of the empty capsules, machinability on the existing filling machines without impacting machine speed, closing integrity after filling, packaging and transport, as well as ease of opening by hand, a new capsule design was developed and tested within the respective patient populations. This new capsule was achieved by modifying the capsule locking mechanism in the closed position from an integral locking ring to partial locking points7. This design change resulted in a four-time reduction of the forces required to separate the cap from the body in the closed position. Usability tests in different patient populations confirmed the significantly improved ease in opening the capsules.

With these technological and regulatory advances, the multiparticulate sprinkle formulation approach has provided new avenues to address the increasing personalisation in medicine development. The technology leverages the benefits of large scale multiparticulate manufacturing combined with the high degree of flexibility for personalisation offered by globally available standard industrial capsule filling. In combination with the easy to open capsule and use in sprinkle form, oral drug administration can be tailored to all kinds of patient populations and with their preferred beverages or soft foods. With multiparticulates formulated as mini-tablets or microspheres for sprinkle administration, along with a specifically designed capsule for easy opening by hand, sprinkle drug delivery systems can achieve their full potential.

REFERENCES 1. https://www.ema.europa.eu/documents/scientific-guideline/reflection-paper-pharmaceutical-development-medicines-use-olderpopulation-first-version_en.pdf 2. https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm563618.pdf 3. https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm610442.pdf 4. Klingmann V. et al Acceptability of Multiple Uncoated Minitablets in Infants and Toddlers: A Randomized Controlled Trial. J Pediatr 201:202-207 (2018) 5. Klingmann V. et al Acceptability of Uncoated Mini-Tablets in Neonates—A Randomized Controlled Trial. J Pediatr 167:893-896 (2015) 6. https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm614401.pdf 7. https://www.capsugel.com/knowledge-center/coni-snap-sprinkle-capsules-brochure

11

the next medicine...

We’ll develop it together.

As a leader for contract development and manufacturing, we at Lonza Pharma & Biotech are recognized for our reliable, high-quality services, global capacity, innovative technology platforms, and extensive experience. Our broad capabilities span across biologics, small molecules, bioconjugates, and cell and gene therapies. © 2018 Lonza. All rights reserved.

We manage projects from pre-clinical stage through commercialization, and our expertise covers both drug substance and drug product.

We believe that the best outcome – for you and for your patients – can only come as a result of a successful collaboration. Together, we can solve the next challenge and bring your next medicine to life.

Visit pharma.lonza.com USA +1 201 316 9200 Japan +81 (0)3 6264 0600 Rest of world +41 61 316 81 11 Email pharma@lonza.com

OSD SUPPLEMENT

CASE STUDY

Who: IMA Group What: Outlines its collaborative study with chemicals company BASF

Case study

How: It assessed its latest coating technology

AN EVEN COAT When deciding on a particular coating technology, manufacturers must consider both the quality and economic efficiency of the process. Consequently, process time and coating uniformity of the final product have to be considered, especially within the realm of functional coating and/or drug layering.

Automated solutions provider IMA Group recently conducted a study alongside chemicals provider BASF to evaluate the efficiency of its Perfima Edge coating technology during the pellet coating process.

Experimental Methods Materials The company used pellets consisting of sucrose and microcrystalline cellulose as a substrate, before applying Riboflavin embedded in a film of PVA-PEG graft copolymer (Table 1).

The functional coat was based on Kollicoat Smartseal 30 D (BASF) – a polymer delivering taste masking functionality due to its pH dependent solubility1. Other components of the formulation (Table 2) include FD & C Blue No. 1 (BASF); acetyl tributyl citrate (ATBC, Jungbunzlauer); buthylene hydroxy toluene (BHT, SigmaAldrich) and talc (Merck).

Equipment

REFERENCE: 1. Kolter, K.; Guth, F.; Angel, M.; Physicochemical characteristics of a new aqueous polymer; AAPS. Annual Meeting and Exposition, November 14–18, 2010, New Orleans, Louisiana, U.S.A.

The study assessed the Perfima Edge side vented pan coater (SVP) which was equipped with wedge wire screen drum, specifically designed for coating small substrates such as pellets. Small wedge wires were fitted into the drum to allow the passage of air during the process.

The equipment maintained the same drum shape, drum geometry and spray system of the standard equipment for tablet coating. To handle all types of substrates in regard to shape and size, specially-designed mixing baffles were welded to the centre and the side walls of the drum.

The coating trials were conducted according to schema reported in Table 3.

13

CASE STUDY

Methods PHOTOMETRICAL MEASURING To determine the individual amount of applied coating, IMA and BASF used photometrical measuring of either Riboflavin or of the Colourant FD&C Blue No. 1. This was done to allow a distinct investigation on the coating level.

DISSOLUTION TESTING Standard equipment according to Ph. Eur. was used for the dissolution test. Phosphate buffer (pH 6.8) was used as dissolution media, due to taste masking function being delivered in the oral cavity. The criterion for a fully functional coat was that no drug release was seen for a period of two hours.

WEIGHT GAIN The weight gain of the pellets was calculated according to the equation in Figure 1.

drug release for 2 hours in neutral media)4. When applying a comparable coating formulation (Table 2) onto pellets, full functionality can be achieved with distinctively lower coating levels (Figure 2). The reason for this is the critical edge between band and cap which every tablet bears inherently. However, pellets with a spherical shape do not offer such crucial areas, meaning reliable functionality is achieved at lower coating levels.

RESULTS AND DISCUSSION In a first coating step, Riboflavin was applied as a tracer for the dissolution testing. The achieved weight gain revealed optimal performance as showed by employing standard deviation as scale for content uniformity (Table 4).

Kollicoat Smartseal 30 D based formulations have to be applied onto tablets with a typical coating level of 3.5 mg/cm² to gain full functionality (meaning no

Due to the mixing properties of the baffles fitted on Perfima Edge, the release profiles become more and more similar

at higher coating levels. This demonstrates that both coating performance and efficiency will be eventually equal.

CONCLUSION The results of the study exemplified the small footprint of the Perfima Edge as a space-saving alternative to fluid bed technology.

More so, the design allows optimal accessibility of the processing, whilst up-scaling is quick and relatively simple.

IMA Active’s wedge wire screen drum was shown to be efficient and able to coat in the same pan cores of different size and shape, the researchers found.

Innovative Roller Compaction BRC 25 and 100 • Minimal material loss due to precise control of the compression force with an innovative electromechanical roller drive • Constant ribbon properties assured with sensitive gap width control

CTION PRODU OF g/h 1-400 k

• Easy handling and short mounting procedures • Hygienic design and effective cleaning by integrated WIP nozzles • Versatile and gentle particle size adjustment with integrated Bohle Turbo Sieve (BTS) • PAT tool integration possible

Suit

uction

tinuous Prod

h and Con able for Batc

• Remote process monitoring possible Are you curious? Schedule your trials now!

www.lbbohle.com

www.continuous-production.com 14

CONTAINMENT SOLUTIONS

FE55 & FE75 WITH CONTAINMENT PACKAGE + Flat valve for a safe product feed + Hermetically-sealed and automatically-locking window flaps + Rapid Transfer Port (RTP) access points for removing or introducing components + Low-dust tablet discharge + Hepa-filter H13 + Human-Machine-Interface (HMI)

www.fette-compacting.com

NEED TO INCREASE

YOUR TABLET PRODUCTION? Multi-Tip Tooling is Your Answer!

Natoli’s multi-tip tooling dramatically increases tablet production without adding a new tablet press, the need for additional space, or adding additional labor and auxiliary equipment. With innovative tooling designs, superior customer service, and a consultative approach, Natoli is your answer.

Contact your Natoli representative...

TODAY!

NATOLI ENGINEERING COMPANY natoli.com • info@natoli.com • +1 636.926.8900

Full radius head