YOUR­INHALATIONGRADE­LACTOSEAs a leader in the field of Inhalation, DFE pharma offers
pharmaceutical industry the most optimal solution for thedevelopment of their Dry Powder Inhalation drug. DFE Pharma isa partner for pharmaceutical companies developing drugs for
pulmonary delivery since many years, with a wide range ofstandard inhalation lactose grades and the option to customize
to meet your needs. Our expertise and three dedicatedinhalation production sites provide an unique starting point for
any advanced pharmaceutical application.

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We are DFE Pharma
We are DFE Pharma: the global
leader in excipient solutions.
We develop, produce and supply
excipients for use in oral solid doseand inhalation formulations, but asa supplier of complete solutions we
do a lot more than that.
We work closely with pharma­
ceutical companies around theworld, collaborating in original
research, supporting their go tomarket strategies and fine-tuning
our products to ensure that their
medicines deliver exactly the rightoutcomes for patients. Thatmakes us more than just a supplier.
We are recognised as a true
partner to the pharmaceuticalindustry in helping people aroundthe world live healthier lives.
We have spent more than 100years in proving that excellence is
not just a word but a deep, longterm commitment to ourcustomers and to the millions ofpatients who use our products
every day.

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Our customers respect us for
product quality, technicalexpertise and hands-on market
support. We work with your futurein mind: today, tomorrow andalways.
Our portfolio consists of filler/binders (Lactose, Micro­crystalline
Cellulose, Starches) and super­disintegrants (Croscarmellose
Sodium and Sodium StarchGlycolate) for oral solid dose, as
well as carriers for inhalation(Lactose).
DFE Pharma, in pursuit ofexcipient excellence.

Your Inhalation Grade Lactose
by DFE Pharma

A growing number of diseases are being treated with inhaled
medicines. Many treatments now use Dry Powder Inhalers, whichinvariably need a high quality inhalation grade of lactose topower the formulation. Since each Dry Powder Inhaler device isdifferent, they often need a specific grade of lactose to ensure
correct product performance, particularly for highly regulated
markets. Due to regulatory demands, all our inhalation grade
lactose is produced in dedicated inhalation production sites.

Quality and Regulatory
SupportAll production sites for inhalation
lactose operate under GMPstandards and meet the high quality
standards that are demanded by
the FDA and other regulatory
bodies. In addition, DFE Pharma
fully supports the quality
requirements demanded by ourcustomers.
A Drug Master File is available toassist in the registration of a new
formulation in the United States.
For optimal control on thefunctionality and to comply withregulatory requirements, additional
testing above the current
pharmacopoeia is in place.
DFE Pharma can support you forregistration of your Dry Powder
Inhalation product in China: formore information, please contact
our regulatory specialist. To support
our customers, an extensive list ofregulatory and quality documentsfor Lactohale® is available at ourwebsite www.dfepharma.com.

Technical Support

Production capabilities

DFE Pharma Inhalation teamdevelops pharmaceutical lactosethat facilitates delivery of youractive to the lung. We work closelywith pharmaceutical companies todesign lactose particles with therequired functionality for the drug,device and filling-platform.

Within DFE Pharma, three
production sites are fully committed
to the production of inhalation
grade lactose, each with theirunique capabilities: Veghel(Netherlands) for production ofRespitose® products, and Borculo(the Netherlands) and Kapuni(New Zealand) for production ofLactohale®. DFE Pharma is the only
excipient supplier with three
production sites on two different
continents for inhalation-grade
lactose, offering customers thepossibility of security of supply. All
three production sites have been
set up to produce a consistentand high-quality inhalation grade
lactose, to meet the quality needsof our customers.

Research and Development
Through our own research and close
co-operation with research
institutes and universities, we arecontinuously expanding ourknowledge of lactose and otherexcipients that can be used forinhaled delivery. Of particularinterest to us is the physiochemical
behaviour of lactose underconditions relevant for use as anexcipient in advanced pharmaceutical applications. With thisknowledge we can advise ourcustomers on the latest scientificdevelopments. DFE Pharma offers
the following inhalation gradelactose brands:• Lactohale®
• Respitose®

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Packaging of Inhalation Lactose
Packaging of the inhalation products offered by DFE Pharma
is important to guarantee the quality and ­stability of thematerial. In the table below, the standard packaging options
for Lactohale® and ­Respitose® are ­listed. Additional packaging
options might be ­available on request.
Storage
It is recommended to store inhalation lactose in the closed original packaging undernormal warehouse ­conditions.

Packaging overview Respitose® and Lactohale®
Packaging attributes

Cardboard
Box NL

Cardboard
Box NZHDPE BoxHDPE Drum

Re-test date

Length (cm)383638.9

38.9-

Width (cm)283232.8

32.8-

Height (cm)454271.4

71.4- Lactohale® 100

20 kg

-

-

-

3 years- Lactohale 200

20 kg

-

-

-

3 years- Lactohale 206

20 kg

-

-

-

3 years- Lactohale® ML001

-

20 kg

-

-

3 years- Lactohale 800

-

20 kg

-

-

3 years- Lactohale 210

15 kg

-

-

-

3 years- Lactohale® 220

15 kg

-

-

-

3 years- Lactohale 230

10 kg

-

-

-

3 years- Lactohale® 300

12.5 kg---

6 months- Respitose ML001

-

-

-

50 kg

3 years- Respitose ML003

-

-

-

40 kg

3 years- Respitose® SV001

--

-

50 kg

3 years- Respitose SV003

-

-

-

50 kg

3 years- Respitose SV010

--

-

50 kg

3 years

Product®
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Lactose-by-Design
Dry Powder Inhalation­Formulations
A dry powder inhaler formulation
should contain drug particles with
an aerodynamic particle size ofless than 5 μm for an optimal­pulmonary delivery. Due to thehigh surface area to mass ratio of
the particulates, the powdereddrug is highly cohesive. Therefore
a larger ­carrier, such as lactose, isapplied to de-agglomerate thedrug particles and optimize thedeposition of the drug in the lung.
In addition, the use of a lactose
carrier has the added benefit ofmaking the formulation manage­
able on an industrial scale byboosting the amount of powderin each dose. Summarizing, boththe filling of a device and the­deposition of the drug in the lungare strongly i­nfluenced by thequality of the carrier.

Role of Lactose in inhaledformulations
Lactose is one of the few excipientsthat have been ­accepted by all­authorities to be used in inhaledformulations. The properties of
the inhalation lactose are chosen
based on the different parameters,
like the device (flow of lactose),
filling platform (flow of lactose),type of drug and how it is processed and the required drug
­release (fine l­actose particles).
In practice, this means that DFE
Pharma can deliver customized­inhalation lactose to meet the­specific requirements of their­customers.

Inhalation lactose is a naturally
occurring disaccharide, which isextensively purified to meet thestrict requirements for use in an­inhaled application. To obtain­different functionalities for the­inhalation formulation the lactose
is further processed by techniquessuch as sieving, milling, micronisation or air-classification.1

More technical information can be foundon our website www.dfepharma.com
1

Steckel, H; Markefka, P; teWierik, H;
Kammelar, R; 2004, Functionality
testing of inhalation grade lactose. Eur.
J. Pharm. Biopharm. 57: 495-505

2

Kinnunen, H.; Hebbink, H.; Peters, H.;
Huck, D.; Makein, L.; Price, P.; Extrinsiclactose fines improve dry powder

The technical publications of DFE
Pharma show how the different
physical properties of inhalation
lactose can be controlled by­blending a fine fraction with acoarse fraction, i.e. the fines­content in inhalation grade­lactose.2 The choice of fines isa critical decision point in the­development of a DPI formulation.
The detailed knowledge of the­experts of DFE Pharma can
support customers to predict­various physical parameters of
the lactose for ­inhalation out offine and coarse lactose fraction.

inhaler formulation performance of acohesive batch of budesonide
via agglomerate formation andconsequential co-deposition;2015 Int J Pharmaceutics 478, 53-59

LactoseSieving

Milling

AirClassification

Micronisation

Blending

5Lactohale®
Lactohale® is our high-quality inhalation grade lactose that can be
optimized and customized to meet the specific need of customer.
Strict and highly consistent particle size control during theproduction, combined with state of the art particle size measuring
techniques form the basis for the success of Lactohale®.
While most customer start theirdevelopment with the standard
Lactohale® grades, many convert
to customization to fine-tune theperformance of their formulation.
In close collaboration, the flow
properties can be matched tothe correct fines content for an
optimal product performance.

in order to ensure that the batchis homogeneous. The resulting­customized Lactohale® grade with
their specific particle size profiles
is unique for each customer.

In the final processing step all­Lactohale® products are blended

Lactohale® Inhalation lactose isproduced in a dedicated inhalation
lactose production sites in Borculo(the Netherlands) and in Kapuni(New Zealand). Both plants were
designed to meet the strict quality

Crystals of alpha monohydrate lactose

Milled alpha monohydrate lactose.

requirements that are demandedby the FDA and supply to commercialized end-product in regulated
markets. We look forward to­collaborate closely with pharma­
ceutical companies to develop,
produce and deliver lactose withthe required functionality.
Please, contact your sales­representative for more
information.

Example of an adhesive mixture of
Lactohale® and salbutamolsulphate.

Lactohale® products overview
Product Name

Type oflactose

Production
Location

Lactohale® 300

Fine

Borculo (NL)

Lactohale 230

Fine

Borculo (NL)Lactohale® 220

Fine

Borculo (NL)

Lactohale 210

Fine

Lactohale ML001
Lactohale® 206

Typical values
Tapped Poured Carr’s
Density Density Index(g/l)(g/l)<5≤10520

260>25%

1.0 – 3.0

<10<30500310>25%

1.5-3.0

11-15

25-40

660

370

>25%

Borculo (NL)

2.0 – 3.5

14 - 1935 - 50

680

400>25%

CoarseKapuni (NZ)

3-7

37-61

124-194

880

570

>25%

CoarseBorculo (NL)

20-50

75-95

115-170

870

720

17%

Lactohale 200

CoarseBorculo (NL)

5-15

50-100120-160

940

650>25%

Lactohale® 800

CoarseKapuni (NZ)

5-15

50-100120-160

940

650>25%

Lactohale 100

CoarseBorculo (NL)

45-65

125-145200-250

840

690

19%

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NL | The Netherlands

6Particle Size Distribution(Sympatec)
D10 (μm)
D50 (μm)
D90 (μm)

NZ | New ZealandRespitose®
Respitose® Inhalation lactose is a highly consistent productwith excellent control of particle size. The offering can bedivided in either sieved crystalline lactose grades withtomahawk-shaped articles (Respitose® SV) or milled lactose
grades with irregular shaped particles (Respitose® ML).
Respitose® product range
include unique lactose gradeswith good flow and strict controlof particle size. Global customers
especially favor the standard
Respitose® SV003 productbecause of its unique particle
size profile.
Respitose® Inhalation lactose isproduced under GMP conditions
at a dedicated inhalation lactose

Respitose® ML001

production site in Veghel, theNetherlands. The plant wasdesigned to meet the strict
quality requirements that aredemanded by the FDA.

Please, contact your sales
representative for more
information.

Combination of differentRespitose® standard grades
provide customers a tool toachieve optimal performancefor their Dry Powder Inhalation
formulation.

Respitose® SV003

Respitose® ML003

Respitose® SV010

Respitose® standard products overview
Product Name

Type oflactose

Production
Location

Particle Size Distribution(Sympatec)
D10 (μm)
D50 (μm)
D90 (μm)

Typical values
Tapped Poured Carr’s
Density Density Index
(g/l)
(g/l)

Respitose® ML003

MilledVeghel (NL)

1-6

20-50

65-140

850

560

>25%

Respitose ML001

MilledVeghel (NL)

3-737-61

124-194

880

570

>25%

Respitose® SV003

SievedVeghel (NL)

19-43

53-66

75-106

780

630

19%

Respitose SV010

SievedVeghel (NL)

35-65

95-125160-190

830

690

17%

Respitose SV001

SievedVeghel (NL)

120-160

210-250

290-350

810

700

14%

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NL | The Netherlands

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DFE Pharma sales offices

Head Office

India

Singapore

Klever Strasse 187

Plot No. 148

3 Temasek Avenue

P.O. Box 20 21 20

Prestige Featherlite Tech Park

#11-01 Centennial Tower

47568 Goch

2nd Phase, EPIP Zone

Singapore 039190

GermanyWhitefield, Bangalore 560066

T. +65 6580 8100

T. +49 2823 9288 770

India

F. +65 6580 8191

F. +49 2823 9288 7799

T. +91 80 4925 6100

pharma@dfepharma.com

F. +91 80 4925 6150

JapanNorth America

China

Taiyo Seimei Bldg. 14F

61 South Paramus Road

Room 302

2-16-2, Konan, Minato-ku, Tokyo

Suite 535

No. 68 Bohang Road

108-0075 JapanParamus, NJ 07652

Pudong Shanghai

T. +81 3 6260 0740

USA

China

F. +81 3 6260 0754

T. +1 551 497 7355

T. +86 21 6134 5821

F. +1 551 497 7358

F. +86 21 6134 5800

BrazilRua Fradique Coutinho, 30 - sala 6105416-000 São Paulo SP Brazil
T. +55 11 2395 1700

dfepharma.com#004 / May 2020

DFE Pharma GmbH & Co. KG - Warranty
The details given here are merely intended for information purposes and are in no way legally binding.
Consequently we accept no responsibility in the broadest sense of the word for damage that may
result from applications based upon this information. ­Furthermore, this information does not constitutepermission to infringe patent and licence rights.

In pursuit of excipient excellence