Antimicrobial and diffusional correlation of N-alkyl betaines and N-alkyl-N,N-dimethylamine oxides from semisolids.
Previous studies have shown that two classes of amphoteric surfactants, N-alkyl betaines and N-alkyl-N,N-dimethylamine oxides, exhibit pronounced antimicrobial activity in combination and have potential for use in a semisolid formulation for topical or vaginal delivery. In this work, several potential delivery systems were prepared and evaluated for antimicrobial activity and diffusional properties. A novel antimicrobial test for semisolids was proposed that determined the contact time needed to kill microorganisms. The unformulated agents in solution exhibited the faster kill within 60 min, followed by the hydroxyethylcellulose gel formulation in 90 min, and the poloxamer gel and a cream that required several hours. Diffusion from the dosage form utilized a Slide-A-Lyzer diffusion cassette with a 10,000 MWCO membrane with (14)C-labeled active species added to the aforementioned antimicrobial formulations. Diffusion of the individual betaine and amine oxide derivatives were tracked over time to determine the diffusion rates and profiles of the components in each formulation and in solution. The betaine derivative diffused up to three times faster than the amine oxide derivative within the first 2 h, but the amount diffused was approximately equivalent at 24 h. The formulations delayed release in the same rank order as the contact time kill analysis: hydroxyethylcellulose gel > poloxamer gel > cream.
Birnie
C R
CR
Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, 600 South 43rd Street, Philadelphia, PA 19104, USA.
Malamud
D
D
Thomulka
K W
KW
Schwartz
J B
JB
Schnaare
R L
RL
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001622:Betaine / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D004123:Dimethylamines / Q000737:chemistry / Q000493:pharmacokinetics*; D004926:Escherichia coli / Q000187:drug effects; D005079:Excipients / Q000493:pharmacokinetics; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D009824:Ointments / Q000493:pharmacokinetics; D010087:Oxides / Q000737:chemistry / Q000493:pharmacokinetics*; D012996:Solutions; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D004123:Dimethylamines; D005079:Excipients; D005765:Gastrointestinal Agents; D009824:Ointments; D010087:Oxides; D012996:Solutions; D001622:Betaine