The suitability of tris(hydroxylmethyl) aminomethane (THAM) as a buffering system for hydroxypropyl methylcellulose (HPMC) hydrophilic matrices containing a weak acid drug.
There are few studies of alkalising pH-modifiers in HPMC hydrophilic matrices. These agents may be incorporated to provide microenvironmental buffering and facilitate pH-independent release of weak acid drugs. This study compared tris(hydroxylmethyl) aminomethane (THAM, TRIS, tromethamine, trometamol) with sodium citrate as internal buffering agents for HPMC (4000 cps) 2208 and 2910 matrices containing felbinac, a weak acid drug which exhibits pH-dependent solubility. Drug release at pH 1.2 and 7.5 was accelerated by both buffers, but THAM-buffered matrices provided extended, diffusion-based release kinetics, without loss of matrix integrity at high buffer concentrations. Release kinetics appeared to be independent of media pH. THAM did not depress the sol-gel transition temperature or suppress HPMC particle swelling, and had minimal effects on gel layer formation. Sodium citrate promoted greater thickness of the early gel layer than THAM. Measurements of internal gel layer pH showed that both buffers produced a rapid alkalisation of the gel layer which was progressively lost. As result of its higher pK(a) and molar ratio on a percent weight basis, THAM provided a higher internal pH and a greater longevity of pH modification. It is concluded that THAM offers a useful buffering option for weak acid drugs in HPMC-based systems.
Pygall
Samuel R
SR
Formulation Insights, School of Pharmacy, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
Kujawinski
Sarah
S
Timmins
Peter
P
Melia
Colin D
CD
D002021:Buffers; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002951:Citrates / Q000737:chemistry; D004058:Diffusion; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D010648:Phenylacetates / Q000737:chemistry; D000077559:Sodium Citrate; D012995:Solubility; D013607:Tablets; D044366:Transition Temperature; D014325:Tromethamine / Q000737:chemistry*
D002021:Buffers; D002951:Citrates; D005079:Excipients; D005782:Gels; D010648:Phenylacetates; D013607:Tablets; D014325:Tromethamine; D000077559:Sodium Citrate; D065347:Hypromellose Derivatives; C012776:biphenylylacetic acid; D008747:Methylcellulose