Transforming growth factor-alpha (TGF-alpha) in a semisolid dosage form: preservative and vehicle selection.
The selection of an ideal semisolid vehicle for growth factors presents a challenge. Some antimicrobial agents are known to delay wound healing. The objective of this investigation was to identify appropriate preservatives and vehicles for TGF-alpha. Criteria for acceptance are noninterference with the mitogenic activity of TGF-alpha as well as adequate product preservation. Vehicles considered were o/w creams, ointments, and a gel. Combinations of six preservatives were tested. Selection was determined using both microbial preservative challenge and TGF-alpha mitogenic assay. In the former, 10 species of microorganisms were inoculated into formulation samples. At selected time intervals, it was determined whether colonies decreased, increased, or remained constant. In the mitogenic assay, samples of either preservatives or formulation prototypes were introduced to TGF-alpha-stimulated fibroblast cell cultures. Mitogenesis was determined by measuring 3H-dThd uptake into newly synthesized DNA. As preservatives, sorbic acid and quaternium-15 appear to satisfy both selection criteria. A thermosetting gel appears most promising as vehicle.
Tan
E L
EL
Bristol-Myers Squibb, Pharmaceutical Research Institute, Pharmaceutics Research and Development, Buffalo, New York 14213-1032.
Shah
H S
HS
Leister
K J
KJ
Kozick
L M
LM
Pasciak
P
P
Vanderlaan
R K
RK
Yu
C D
CD
Patel
B
B
D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004655:Emulsions; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008934:Mitogens; D014677:Pharmaceutical Vehicles; D011310:Preservatives, Pharmaceutical; D013936:Thymidine / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000008:administration & dosage* / Q000737:chemistry
D004655:Emulsions; D008934:Mitogens; D014677:Pharmaceutical Vehicles; D011310:Preservatives, Pharmaceutical; D016211:Transforming Growth Factor alpha; D004247:DNA; D013936:Thymidine