Mannogem® Mannitol Pharmaceutical Excipient Mannogem® Mannitols Mannitol 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
Chemical Stability Hygroscopicity of Mannogem EZ Compared to MCC Mannitol contains only hydroxyl groups, which are less 5 reactive than aldehydes and ketones. Mannitol does Mannogem at 25 C not promote acid-base reactions, oxidation or undergo 2 MCC 2 at 25 C
Maillard reaction with primary amines. Mannitol is stable s s a
to heat, melting without decomposition, and is capable m
r of forming stable crystalline polymorphs. In addition, low levels of reducing sugar impurities make mannitol a t e n superior choice for formulating. t
C o n 6 e u r t s o i
Solubility M 3 Mannitol dissolves rapidly while retaining porosity making it the excipient of choice in lyophilized and directly compressible orodispersible formulations. This 2 3 4 5 6 7 easily wettable binder is excellent in solid dispersion for elati e umi it improving the solubility of poorly soluble APIs.
Minimal Moisture Content Low 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-Cariogenic Mannitol has low calorie content and does not contribute to tooth decay.
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Organoleptic Properties Mannitol 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 Sweetness to Sucrose Relative Cooling Effect (cal/g)
Su rose Su rose
Maltitol Maltitol
Sor itol Sor itol
litol litol
Mannitol Mannitol
2 4 6 5 5 2 25 3 35
THE MANNOGEM ADVANTAGE Our 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 Dry Blending of Micronized and Swallow Tablets Low Dose Actives Orally Disintegrating Tablets Direct Compression Chewable Tablets and Lozenges Mannogem EZ Roller Compaction Effervescent Tablets Hard Gelatin Capsules Sachets and Stick Packs Direct Compression Swallow Tablets Dry Blending Chewable Tablets and Lozenges Mannogem Granular Roller Compaction Tablets with Taste Masked APIs Mannogem 2080 Hard Gelatin Capsules Sachets and Stick Packs Wet Granulation Swallow Tablets Hot Melt Extrusion Pellets (especially Proton Pump Inhibitors) Wet Mass Extrusion and Liquid Suspensions/Syrups Mannogem Powder Spheronization Lyophilization Spray-Dry Coprocessing
3 Direct Compression Grades 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 EZ Spray Dried SEM Mannogem EZ (100x Magnification) The 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 SPI Spray-Dried Mannitol EZ 100x for ordered mixing with micronized APIs and low dose formulations.
Mannogem Granular Grades Both 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 Granular Mannogem 2080 Mannogem Granular has a larger particle size that has Mannogem 2080 has a smaller average particle size, and shown to contribute to a softer texture for chewable a tighter overall particle size range. This lower particle tablets. The larger particle size allows it to match size produces a higher surface area relative to Mannogem specific particle size and density constraints to minimize Granular, making it an effective API carrier system. segregation during transport and manufacturing.
SEM Mannogem Granular (100x Magnification) SEM Mannogem 2080 (100x Magnification)
SPI Granular Mannitol 100x SPI Granular Mannitol 2080 100x
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Compactibility
2 Mannogem ranular 2 Mannogem ranular High Compactibility 6 Mannogem
Mannogem direct compression grades are highly compactible and gain hardness rapidly with increasing e s n r 2 compression force. The high binding capacity of Mannogem a makes it an excellent tablet binder, capable of producing a let lo e arma quality, robust tablets at lower compression forces. Station nstrumente ress 25 M 55 2 un es a let eig t 7 mg mg stearate 2 5 4 5 2 25 Com ression or e
Disintegration vs Hardness (no disintegrant added)
Mannogem ranular 2 Mannogem ranular Excellent Disintegration Mannogem 7 5 Mannogem direct compression grades are readily soluble n i m and typically exhibit shorter disintegration times, without the e m i
aid of disintegrants, that are independent of tablet hardness. n
o 6 ti
a These grades are easily wettable and dissolve rapidly, leading r e g t
n to increased drug release. Shorter disintegration times may i s i
lo e arma 4 5 Station nstrumente ress help to enhance dissolution of poorly soluble drugs. 25 M 55 2 un es a let eig t 7 mg mg stearate 2 5 3 4 6 2 4 6 a let ar ness
Friability
2 lo e arma Mannogem ranular 2 Station nstrumente ress Mannogem ranular 25 M 55 2 un es Low Friability Mannogem a let eig t 7 mg 5 mg stearate 2 5 Mannogem products form durable, robust tablets with low friability that can withstand the stresses associated with film
t coating, printing and packaging. i l i a i r
5
5 2 25 Com ression or e
5 Deformation Mechanism Imparts Formulation Benefits Mannitol 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.
Tablet Hardness vs. Dwell Time in Milliseconds (Mannogem EZ)
22 Allows High Speed Production 3 ms Mannogem has low sensitivity to press speed and can 2 ms 3 ms be tabletted over a wide range of dwell times. Higher ms production rates are possible with Mannogem direct 4 e s
compression grades because tablet robustness is not n r
compromised with increased press speeds. a t e
l a
Manest eta ress 6 2 4 6 M 625 un es a let eig t mg SS 2 5 2 5 5 2 25 3 35 Com ression or e
Lubrication Sensitivity
2 Mannogem at 2 min Mannogem at 3 min Low Sensitivity to Lubricant Levels and Over Blending 6 Mannogem 2 at 2 min The increased surface area resulting from the brittle Mannogem 2 at 3 min fracture deformation exposes clean new surfaces for s 2 bonding that reduce mannitol's sensitivity to lubricant n e s r a levels and extended blending times. a let
lo e arma 4 Station nstrumente ress 25 M 55 2 un es a let eig t 7 mg mg stearate 2 5 5 5 2 25 Com ression
6 Product Sales Bulletin Powder Grade Mannogem Mannitol Powder is an excellent tablet diluent/ SEM Mannogem Powder (100x Magnification) 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.
SPI Mannitol POWDER
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ANTACID ACTIVES FUNCTIONAL EXCIPIENTS The global leader in immediate-relief antacid Ingredients and formulation expertise to support a actives, we specialize in aluminum, magnesium, wide range of patient friendly dosage forms. calcium products, and preformulated solutions for the production of antacid suspensions and tablets. VACCINE ADJUVANTS Years of expertise in aluminum hydroxide chemistry DRUG DELIVERY SYSTEMS ensure our vaccine adjuvants exhibit a very regular A full spectrum of ODT products, services, and profile in terms of compliance, morphology, particle technologies to support every stage of your size distribution, and protein adsorption capacity. product life cycle. DRUG DEVELOPMENT SERVICES TASTE-MASKED ACTIVES Our complete drug development and testing service Our Actimask® technology provides an excellent can provide unique options to energize your drug taste barrier and mouthfeel without hindering API portfolio. No time? Limited resources? release and onset of therapeutic relief. We can deliver your project to you.
7 Mannogem® Mannitol
Typical Properties Bulk Density Tapped Density Avg. Particle Size Product Carr's Index g/mL g/mL 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 not intended to be product specifications.
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© SPI Pharma 2016. All trademarks are the property of SPI Pharma. The information contained in this document is proprietary to SPI Pharma and Order No. SPI-EXC-MGM-0100-03201600 may not be used or disseminated inappropriately. The information and recommendations contained herein are to the best of SPI Pharma, Inc.’s 03-2016 | All rights reserved 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.