374
`
`Monnitol
`
`SEM: 2
`Excipient: Mannitol
`Manufacturer: Merck
`Magnification: 500 x
`Voltage: 3.5 kV
`
`SEM:4
`Excipient: Mannitol granular
`Manufacturer: SPI Polyols Inc.
`Lot No: 2034F8
`Magnification: 100 x
`
`00005559
`
`-
`
`10µm
`
`MERCK REM-Team
`
`SEM: 3
`Excipient: Mannitol powder
`Manufacturer: SPI Polyols Inc.
`Lot No: 3140G8
`Magnification: 100 x
`
`Osmolarity: a 5.07% w/v aqueous solution is isoosmotic with
`serum.
`Particle size distribution:
`Pear/ital 300 DC: maximum of 0.1 % greater than 500 µm
`and minimum of 90% greater than 200 µmin size
`Pear/ital 400 DC: maximum of 20% greater than 500 µm
`and minimum of 85% greater than 100 µm in size
`Pear/ital 500 DC: maximum of 0.5% greater than 841 µm
`and minimum of 90% greater than 150 µm in size
`Average particle diameter is 250 µm for Pear/ital 300
`DC, 360 µm for Pearlitol 400 DC and 520 µm for Pear/ital
`500 DC.(ZlJ See also Figure 3.
`Refractive index: nf>0 = 1.333
`Solubility: see Table II.
`Specific surface area: 0.37--0.39 m2/g
`Table I:
`Pharmacopeial specifications for mannitol.
`
`Test
`
`JP 2001
`
`PhEur 2002 USP 25
`
`+
`
`+
`
`Identification
`+
`Characters
`+
`Solution appearance +
`+
`l 65-l 70°C 164-169°C
`166-169°C
`Melting range
`Specific rotation
`+ 137° to + 145°+23° to +25° + 137° to+ 145°
`Conductivity
`+
`Acidity
`Loss on drying
`Chloride
`Sulfate
`Arsenic
`Lead
`Nickel
`Heavy metals
`Reducing sugars
`Residue on ignition
`Related substances
`Bacterial endotoxins
`Microbial
`
`,;; 0.5%
`
`+
`,;; 0.3%
`,;; 0.007%
`,;; 0.01 %
`,;; l ppm
`
`,;; 0 .5ppm
`,;; l ppm
`
`,;; 0.2%
`
`+
`
`,;; 0.1%
`,;; 41U/g10l
`,;; 100/g
`
`IO Typical Properties
`Compressibility: see Figure 1.
`Density (bulk):
`0.430 g/cm3 for powder
`0. 7 g/cm3 for granules
`Density (tapped):
`0. 734 g/cm 3 for powder
`0.8 g/cm3 for granules
`Density (true): l.514g/cm3
`Dissociation constant: pK. = 13.5 at 18°C
`Flash point: < 150°C
`Flowability: powder is cohesive, granules are free flowing.
`Heat of combustion: 16.57 kJ!g (3.96 Kcal/g)
`Heat of solution: -120.9 Jig (-28.9 cal/g) at 25°C
`Melting point: l66-l68 °C
`Moisture content: see Figure 2.
`
`+
`,;;0.3%
`,;; 0.007%
`,;; 0 .01%
`,;; 1.3 ppm
`
`+
`,;; 5ppm
`+
`,;; 0 .10%
`
`!ol Test applied only if the mannitol is to be used in the manufacture of parenteral dosage forms.
`
`0-101.5%
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1023, p. 13 of 24
`
`