Mannogem Mannitol - ¥Effervescent Tablets ... Mannogem Mannitol Powder is an excellent tablet diluent/ ... We can deliver your project to you. merias S arma n

Mannogem® Mannitol Pharmaceutical Excipient

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Mannogem® MannitolsMannitol is becoming more popular as a filler/binder in formulations because of its chemical stability, low hygroscopicity, solubility and organoleptic properties. It has favorable tabletting characteristics that produce robust tablets with good disintegration. Mannitol is a versatile excipient that is ideal for the formulation development and manufacturing of a wide range of patient friendly dosage forms:

¥¥ Swallow Tablets¥¥ Chewable Tablets and Lozenges¥¥ Orally Disintegrating Tablets ¥¥ Orally Dispersible Powders¥¥ Effervescent Tablets¥¥ Hard Gelatin Capsules

Hygroscopicity of Mannogem EZ Compared to MCC

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6

9

12

15

0 10 20 30 40 50 60 70 80 90 100

Moi

stur

e Co

nten

t (%

dry

mas

s)

Relative Humidity (%)

Mannogem EZ at 25°C

MCC 102 at 25°C

Chemical StabilityMannitol contains only hydroxyl groups, which are less reactive than aldehydes and ketones. Mannitol does not promote acid-base reactions, oxidation or undergo Maillard reaction with primary amines. Mannitol is stable to heat, melting without decomposition, and is capable of forming stable crystalline polymorphs. In addition, low levels of reducing sugar impurities make mannitol a superior choice for formulating.

SolubilityMannitol dissolves rapidly while retaining porosity making it the excipient of choice in lyophilized and directly compressible orodispersible formulations. This easily wettable binder is excellent in solid dispersion for improving the solubility of poorly soluble APIs.

Minimal Moisture ContentLow hygroscopicity adds protection against moisture to safeguard the chemical and physical stability of the API and excipients within a formulation. Without hydrate formation or water retention, faster drying and processing times are possible during wet granulation and coprocessing applications.

Low Calorie and Non-CariogenicMannitol has low calorie content and does not contribute to tooth decay.

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Product Sales Bulletin

Organoleptic PropertiesMannitol has a negative heat of solution which imparts a pleasant cooling sensation. Due to the fast dissolving property of mannitol, it quickly delivers excellent palatability through a creamy texture and a mild sweetness. These characteristics make it an ideal excipient for the formulation of convenient, patient friendly dosage forms that are easy to administer.

Relative Cooling Effect (cal/g)Relative Sweetness to Sucrose

THE MANNOGEM ADVANTAGEOur extensive experience in polyol chemistry enables SPI Pharma to offer a range of Mannogem Mannitol product options for all oral dosage formulation applications. We focus solely on products for the pharmaceutical market that are engineered to provide customized solutions to meet our customers' specific processing needs.

PRODUCT GRADE TARGET APPLICATION TARGET DOSAGE FORM

Mannogem EZ

Dry Blending of Micronized and Low Dose Actives Direct Compression Roller Compaction

Swallow TabletsOrally Disintegrating TabletsChewable Tablets and LozengesEffervescent TabletsHard Gelatin CapsulesSachets and Stick Packs

Mannogem Granular Mannogem 2080

Direct CompressionDry Blending Roller Compaction

Swallow TabletsChewable Tablets and LozengesTablets with Taste Masked APIsHard Gelatin CapsulesSachets and Stick Packs

Mannogem Powder

Wet Granulation Hot Melt Extrusion Wet Mass Extrusion and Spheronization LyophilizationSpray-Dry Coprocessing

Swallow TabletsPellets (especially Proton Pump Inhibitors)Liquid Suspensions/Syrups

0% 20% 40% 60% 80% 100%

Mannitol

Xylitol

Sorbitol

Maltitol

Sucrose

0 5 10 15 20 25 30 35

Mannitol

Xylitol

Sorbitol

Maltitol

Sucrose

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Direct Compression Grades

Mannogem Granular GradesBoth Mannogem Granular and Mannogem 2080 are manufactured through a wet granulation process and have a larger particle size than our Mannogem EZ spray dried material. They exhibit excellent flow, disintegration and compression properties. These products are ideal for formulating tablets with taste masked APIs, which often have a larger particle size due to the taste masking process.

Mannogem EZ Spray DriedThe proprietary process used to manufacture Mannogem EZ yields a porous material with lower disintegration times, a narrow particle size distribution, enhanced flow, and compression properties. It is due to these properties that Mannogem EZ is excellent in ODT formulations. It produces tablets with higher hardness than other excipients at comparable compression forces, and its higher surface area allows Mannogem EZ to work well as a base for ordered mixing with micronized APIs and low dose formulations.

Mannogem Mannitols are available in a number of functional grades to meet the specific application needs of the formulator. To ensure consistent blend and tablet content uniformity results, select the grade that best meets the specific requirements of individual formulations based on particle size and density properties of the API and other components in the formulation.

Mannogem 2080Mannogem 2080 has a smaller average particle size, and a tighter overall particle size range. This lower particle size produces a higher surface area relative to Mannogem Granular, making it an effective API carrier system.

SEM Mannogem EZ (100x Magnification)

SPI Spray-Dried Mannitol EZ 100x

SEM Mannogem Granular (100x Magnification)

SPI Granular Mannitol 100x

SEM Mannogem 2080 (100x Magnification)

SPI Granular Mannitol 2080 100x

Mannogem Granular Mannogem Granular has a larger particle size that has shown to contribute to a softer texture for chewable tablets. The larger particle size allows it to match specific particle size and density constraints to minimize segregation during transport and manufacturing.

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High Compactibility Mannogem direct compression grades are highly compactible and gain hardness rapidly with increasing compression force. The high binding capacity of Mannogem makes it an excellent tablet binder, capable of producing quality, robust tablets at lower compression forces.

Compactibility

Low Friability Mannogem products form durable, robust tablets with low friability that can withstand the stresses associated with film coating, printing and packaging.

Friability

Excellent Disintegration Mannogem direct compression grades are readily soluble and typically exhibit shorter disintegration times, without the aid of disintegrants, that are independent of tablet hardness. These grades are easily wettable and dissolve rapidly, leading to increased drug release. Shorter disintegration times may help to enhance dissolution of poorly soluble drugs.

Disintegration vs Hardness (no disintegrant added)

40

80

120

160

200

10 15 20 25

Tabl

et H

ardn

ess

(N)

Compression Force (kN)

Mannogem Granular 2080

Mannogem Granular

Mannogem EZ

Globe Pharma 8 Station Instrumented Press25 RPM0.5512" FFBE PunchesTablet Weight: 700mgmg stearate: 2.5%

3.0

4.5

6.0

7.5

9.0

40 60 80 100 120 140 160

Disi

nteg

ratio

n Ti

me

(min

)

Tablet Hardness (N)


Mannogem Granular

Mannogem EZ


0.0%

0.5%

1.0%

1.5%

2.0%

10 15 20 25

Fria

bilit

y (%

)



Mannogem Granular

Mannogem EZ


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Deformation Mechanism Imparts Formulation BenefitsMannitol is a brittle material that fractures under compression. Brittle fracture deformation results in the constant creation of new surfaces during compression. This characteristic allows mannitol to be less sensitive to lubricant levels and blend times. It also contributes to enhanced compactibility, producing robust tablets independent of dwell time.

Allows High Speed ProductionMannogem has low sensitivity to press speed and can be tabletted over a wide range of dwell times. Higher production rates are possible with Mannogem direct compression grades because tablet robustness is not compromised with increased press speeds.

Tablet Hardness vs. Dwell Time in Milliseconds (Mannogem EZ)

Low Sensitivity to Lubricant Levels and Over BlendingThe increased surface area resulting from the brittle fracture deformation exposes clean new surfaces for bonding that reduce mannitol's sensitivity to lubricant levels and extended blending times.

Lubrication Sensitivity

20

60

100

140

180

220

5 10 15 20 25 30 35

Tabl

et H

ardn

ess

(N)


39 ms20 ms13 ms10 ms

Manesty Beta Press20, 40, 60, 80 RPM0.625" FFBE PunchesTablet Weight: 1000 mgSSF 2.5%

0

40

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Tabl

et H

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N)

Compression (kN)

Mannogem EZ at 2 min

Mannogem EZ at 30 min

Mannogem 2080 at 2 min

Mannogem 2080 at 30 min


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Mannogem Mannitol Powder is an excellent tablet diluent/filler for use in wet granulation and lyophilization. It dries rapidly, resulting in shorter processing time and increased productivity.

Mannitol is also a good excipient for hot melt extrusion applications. It melts without decomposition at a temperature of approximately 165° C. Its rapid recrystallization upon cooling make it an attractive carrier to improve solubility of poorly soluble APIs.

Powder GradeSEM Mannogem Powder (100x Magnification)

SPI Mannitol POWDER

OUR PRODUCTS AND SERVICES CAN HELP YOU TO SOLVE THE MOST CHALLENGING FORMULATION PROBLEMS– EFFICIENTLY, COST-EFFECTIVELY AND WITH A FOCUS ON SERVICE.

ANTACID ACTIVES The global leader in immediate-relief antacid

actives, we specialize in aluminum, magnesium, calcium products, and preformulated solutions for the production of antacid suspensions and tablets.

DRUG DELIVERY SYSTEMSA full spectrum of ODT products, services, and

technologies to support every stage of your product life cycle.

TASTE-MASKED ACTIVESOur Actimask® technology provides an excellent

taste barrier and mouthfeel without hindering API release and onset of therapeutic relief.

FUNCTIONAL EXCIPIENTS Ingredients and formulation expertise to support a

wide range of patient friendly dosage forms.

VACCINE ADJUVANTS Years of expertise in aluminum hydroxide chemistry ensure our vaccine adjuvants exhibit a very regular

profile in terms of compliance, morphology, particle size distribution, and protein adsorption capacity.

DRUG DEVELOPMENT SERVICESOur complete drug development and testing service

can provide unique options to energize your drug portfolio. No time? Limited resources?

We can deliver your project to you.

AmericasSPI Pharma, Inc.Rockwood Office Park503 Carr Rd., Suite 210Wilmington, DE 19809

Europe/Middle East/ AfricaSPI Pharma SASChemin du Vallon du Maire13240 Septemes-Les VallonsFrance

Asia/PacificSPI Pharma, Inc – India Branch21 B, Veerasandra Industrial AreaHosur Road, Bangalore – 560100Karnataka, India

Australia Distribution CompanyAnzchem1 Braidwood StreetEnfield NSW 2136Australia

Contact Us:[email protected]

www.spipharma.com

© SPI Pharma 2016. All trademarks are the property of SPI Pharma. The information contained in this document is proprietary to SPI Pharma and may not be used or disseminated inappropriately. The information and recommendations contained herein are to the best of SPI Pharma, Inc.’s knowledge reliable and accurate. Any recommendations are made without warranty, either implied or expressed, due to the variations in equipment, conditions, and methods which may be used in commercially processing the products. No warranties of any kind are made, express or implied, including those of merchantability and fitness for particular purpose, other than the products conform to current standard specifications. SPI Pharma, Inc. makes no warranty that the use of the products or formulations provided by SPI Pharma, Inc. will not infringe any trademark, trade name, copyright, patent or other rights held by any third party when used in customer’s application. SPI Pharma, Inc. shall not be liable for loss of profit or for incidental, special or consequential loss or damages.

Order No. SPI-EXC-MGM-0100-03201600 03-2016 | All rights reserved

Mannogem® Mannitol

Product Bulk Density g/mL

Tapped Density g/mL Carr's Index Avg. Particle Size

d(0.5)

Mannogem Powder 0.45 0.68 34 ≈60

Mannogem EZ 0.44 0.56 21 ≈140

Mannogem 2080 0.56 0.67 16 ≈300

Mannogem Granular 0.62 0.70 11 ≈400

Typical Properties

*Typical properties not intended to be product specifications.

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Mannogem Mannitol - ¥Effervescent Tablets ... Mannogem Mannitol Powder is an excellent tablet diluent/ ... We can deliver your project to you. merias S arma n