Hydroxypropylmethylcellulose - an overview

30 Dec.,2022


Hydroxypropyl Methyl Cellulose

2.5.4 Hydroxylpropyl Methylcellulose (HPMC)

HPMC is a water soluble nonionic cellulosic polymer in which some of the hydroxyl groups are substituted with methoxy and hydroxypropyl groups (Zarmpi et al., 2017). As a binder, HPMC is used at the concentration of 2%–5% w/w, however, it has been commonly used as tablet film coating polymer. The polymer chain length, size and degree of branching determine the viscosity of the polymer in solution. In general, a tablet film coating requires low viscosity polymers. Using low viscosity polymers, the solid content in the coating formulation can be increased with a lesser amount of water, which can increase coating speed and efficiency. HPMC has many of the desired coating polymer properties. It provides aqueous soluble films; easy processing because of its nontacky nature; a transparent, tough, and flexible film that protects fragile tablets; improved appearance; and resistance to abrasion. The lower viscosity HPMC, however, produced film with lower tensile strength. The higher viscosity grades of HPMC provide film with good tensile strength, but their films have poor adhesion to the core surface and can easily peel off the tablet surface. When used alone, HPMC has the tendency to bridge or fill the debossed tablet surfaces. Therefore, a mixture of HPMC with other polymers or plasticizers is used to improve its binding to the tablet surface and eliminate bridging or filling problems.

Different grades of HPMC are available according to their particle size distribution, viscosity, molecular weights, and substitution of methoxy and hydroxypropyl groups. Because water penetration affects drug release and dissolution, not only the hydroxypropyl group and the degree of substitution but also the substitution pattern affects the release and dissolution (Zarmpi et al., 2017). Heterogeneity in the substitution pattern alters the release of the polymer because of hydrophobic interactions between the substituent, and a subsequent drug release alteration (Viriden, Larsson, & Wittgren, 2010; Zhou et al., 2014). Variation in substitution pattern causes batch-to-batch variability (Dahl, Calderwood, Bormeth, Trimble, & Piepmeier, 1990). On aqueous solutions interaction, HPMC hydrates and forms a viscous gel layer that thickened when more water penetrated. These characteristics of HPMC affect its functionality. The MW and chain length has a significant effect on the viscosity of HPMC aqueous solutions and affects drug release and dissolution (Zarmpi et al., 2017). The hydrogen-bonding between oxygen atoms in ether groups of HPMC and water molecules leads to extension of the polymer and formation of a coil-shaped structure (Zarmpi et al., 2017). Coiled structures tend to form more hydrogen-bonds, entrap water, and form entanglements with other coiled molecules resulting in increased resistance to flow. Therefore, HPMC with high MW tends to swell faster and forms viscous layers.

Particle size of HPMC affects drug release and dissolution through its impact on tablet hardness and water penetration. HPMC of smaller particle size formed stronger tablets because of increased surface area and interparticle cohesiveness, whereas HPMC of larger particles enhanced the dissolution because they do not fully occupy the space around each particle, leaving voids for water penetration (Mohamed et al., 2015). Drug release was caused by disintegration, diffusion, and a combination of diffusion and erosion for large, medium, and small particle sizes of HPMC, respectively. These effects were attributed to the proximity of polymer particles and the differences in the porosity of the formed hydrogel. Faster dissolution observed with higher HPMC particle sizes because of their porous arrangement, was counterbalanced via high concentrations because more polymer chains were present leaving no spaces for water penetration. The drug release rate from HPMC matrices was influenced by the drug/HPMC ratio, drug solubility, compression force, and viscosity grade of the HPMC. Lower viscosity grade HPMCs are more sensitive to the effect of compression force and tend to provide erosion-based release, compared to higher viscosity grade HPMCs for predominantly diffusion-based drug release (Hiremath & Saha, 2008a, 2008b). Mechanical properties of HPMC also affect its functionality. According to Rowe, dense granules are expected when the spreading coefficient of binder over substrate was positive, while negative spreading coefficient led to the formation of porous granules (Rowe, 1990). Hydroxypropyl cellulose (HPC) is also one of the widely used binders (Parikh, 2010). HPC is nonionic, water-soluble, and pH insensitive cellulose ether polymer. The high level of substitutions makes HPC more thermoplastic and less hygroscopic than other water soluble cellulose ethers. Although, HPC has a good film formation property and excellent plasticity, it is not commonly used as an aqueous film coating polymer compared to HPMC because of its strong binding force. Various MW grades of HPC are available; however, low MW grades are typically used as binders. To overcome the above bridging or filling issues of HPMC, the combination of HPMC and HPC are used. HPC provides better film adhesion; however, the cost of HPC is much higher than HPMC.