Chemistry Reference
In-Depth Information
Figure 2.4.
Chemical representation of p(MAA-
co
-EA).
Figure 2.5.
Representative structure of HPMC.
2.1.2.4 Hydroxypropylmethylcellulose (Hypromellose)
S
TRUCTURE AND
S
YNTHESIS
/P
HYSICAL
P
ROPERTIES
The base material for HPMC is
cellulose, a natural polymer that is abundant in plants as the primary component of plant
cell walls. Cellulose is an extremely long (MW
10
6
Da), highly stereoregular
polysaccharide composed of anhydroglucose units (AGUs) [14].
HPMC, depicted in Figure 2.5, is made by reaction of cellulose with methyl
chloride, propylene oxide, and caustic soda. There are three available OH groups of
cellulose and the resulting substituents R
1
,R
2
, and R
3
are predominantly CH
3
,H,
CH
2
CH(OH)CH
3
, and CH
2
CH(OCH
3
)CH
3
[15]. The last substituent is formed by
further methylation of a hydroxypropyl moiety.
The substitution degree of HPMC is characterized by weight percent of methoxy and
hydroxypropoxy groups obtained by Zeisel cleavage with hydrogen iodide [16]. The
USP de
>
1
×
nes four substitution types according to the content of methoxy and hydrox-
ypropoxy groups.
HPMC is available in a wide range of viscosities (measured 2 wt% in water; for
viscosity
-
molecular weight relationship, see Ref. 17) The high-viscosity grades (about
4000
100,000 mPa s) are often used in hydrophilic matrix tablets, while lower viscosity
grades (3
-
-
15 mPa s), produced by acid-catalyzed cleavage of the cellulose backbone, are
excellent
film formers and frequently used in tablet coating and capsule manufacture [18].
Table 2.3 shows the types of substitution for HPMC. Glass transition temperatures (
T
g
)
of HPMC are reported in the literature ranging from about 155 to 180
C [19]. The
equilibrium moisture content at 75% relative humidity (RH) was determined to be about
10% for a 2910 substitution-type HPMC [20], which is at the lower end of the range
found across HPMC substitution grades. The maximum reported water uptake is in the
range of 15
°
18% at 75% RH for 2208 substitution type [21]. The substitution type most
commonly used for preparing ASDs by a solvent evaporation technology is 2910, as it is
suf
-
ciently soluble in a range of organic solvents. In addition, this grade is available in
