Compression and compaction properties of plasticised high molecular weight hydroxypropylmethylcellulose (HPMC) as a hydrophilic matrix carrier.
The compression and compaction properties of plasticised high molecular weight USP2208 HPMC were investigated with the aim of improving tablet formation in HPMC matrices. Experiments were conducted on binary polymer-plasticiser mixtures containing 17 wt.% plasticiser, and on a model hydrophilic matrix formulation. A selection of common plasticisers, propylene glycol (PG) glycerol (GLY), dibutyl sebacate (DBS) and triacetin (TRI), were chosen to provide a range of plasticisation efficiencies. T(g) values of binary mixtures determined by Dynamic Mechanical Thermal Analysis (DMTA) were in rank order PG>GLY>DBS>TRI>unplasticised HPMC. Mean yield pressure, strain rate sensitivity (SRS) and plastic compaction energy were measured during the compression process, and matrix properties were monitored by tensile strength and axial expansion post-compression. Compression of HPMC:PG binary mixtures resulted in a marked reduction in mean yield pressure and a significant increase in SRS, suggesting a classical plasticisation of HPMC analogous to that produced by water. The effect of PG was also reflected in matrix properties. At compression pressures below 70 MPa, compacts had greater tensile strength than those from native polymer, and over the range 35 and 70 MPa, lower plastic compaction values showed that less energy was required to produce the compacts. Axial expansion was also reduced. Above 70 MPa tensile strength was limited to 3 MPa. These results suggest a useful improvement of HPMC compaction and matrix properties by PG plasticisation, with lowering of T(g) resulting in improved deformation and internal bonding. These effects were also detectable in the model formulation containing a minimal polymer content for an HPMC matrix. Other plasticisers were largely ineffective, matrix strength was poor and axial expansion high. The hydrophobic plasticisers (DBS, TRI) reduced yield pressure substantially, but were poor plasticisers and showed compaction mechanisms that could be attributed to phase separation. The effect of different plasticisers suggests that the deformation characteristics of this HPMC in the solid state is dominated by hydroxyl mediated bonding, rather than by hydrophobic interactions between methoxyl-rich regions.
Hardy
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Formulation Insights, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Cook
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WG
Melia
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CD
D002626:Chemistry, Pharmaceutical; D003998:Dicarboxylic Acids / Q000737:chemistry; D004337:Drug Carriers; D004548:Elasticity; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D008970:Molecular Weight; D010968:Plasticizers / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011312:Pressure; D011409:Propylene Glycols / Q000737:chemistry*; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D013718:Tensile Strength; D014215:Triacetin
D003998:Dicarboxylic Acids; D004337:Drug Carriers; D010968:Plasticizers; D011108:Polymers; D011409:Propylene Glycols; D013607:Tablets; C012504:polypropylene glycol; D065347:Hypromellose Derivatives; C055481:dibutyl sebacate; D008747:Methylcellulose; D014215:Triacetin