Effect of EDTA and methionine on preventing loss of viscosity of cellulose-based topical gel.
Methylcellulose and hydroxypropylmethylcellulose (hypromellose) are used in topical formulations of a protein to form a viscous hydrogel. Five lots of hypromellose raw material were made into 3% gel; all showed viscosity loss after sterilization by autoclave. EDTA (edetate disodium) minimized the viscosity loss caused by autoclaving in the presence of up to 100 ppm H(2)O(2). These results suggest that EDTA may prevent loss of viscosity of the hydrogel when peroxide is present. H(2)O(2) at low levels (2-50 ppm) caused significant viscosity loss over time at either 40 degrees C or 5 degrees C in 3% methylcellulose or hypromellose gel. EDTA slowed the rate of viscosity loss during storage under stress by H(2)O(2) but did not completely prevent the loss. Methionine was effective in completely preventing gel-viscosity loss during storage in the presence of up to 50 ppm H(2)O(2). On the basis of these results, it is recommended that methionine be added to the protein topical formulation as a stabilizer against viscosity loss.
Ji
Junyan A
JA
Late Stage Pharmaceutical and Processing Development, Process Research and Development, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. jji@gene.com
Ingham
Erika
E
Wang
John Y
JY
D004492:Edetic Acid / Q000494:pharmacology*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D065347:Hypromellose Derivatives; D008715:Methionine / Q000494:pharmacology*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D013242:Sterilization; D013696:Temperature; D014783:Viscosity
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D004492:Edetic Acid; D008715:Methionine; D006861:Hydrogen Peroxide