Application of an oily gel formed by hydrogenated soybean phospholipids as a percutaneous absorption-type ointment base.
We investigated the possibility of developing an oily gel formed by hydrogenated soybean phospholipids (HSL) as a percutaneous absorption-type ointment base. Liquid paraffin (LP) was used as the oil, and indomethacin (IM), ketoprofen (KP), flurbiprofen (FP) and ibuprofen (IP) were used as model drugs. IM did not dissolve in LP, but solubilized when heated with HSL at a concentration of about 1% with 15% HSL at 95 degrees C. IM gel was thus prepared as follows: IM and HSL were mixed, added into LP, capped tightly, heated in a water bath and cooled. The consistency of the gel increased with increasing IM concentration, indicating some kind of interaction between IM and HSL. The release of IM from the IM gel was faster than that from a preparation in which IM was mixed in gel at room temperature (Gel + IM). The release rate of IM from IM gel was proportional to IM concentrations up to 1%, but became constant above that. Permeation of IM through hairless rat abdominal skin from IM gel was higher than that from the Gel + IM. The permeation rate was proportional to IM concentrations in the range of 0.1 to 0.5% in 15% HSL gel. KP and FP also solubilized in gel when subjected to the same procedure as IM, and their release and permeation increased when they were formulated as gels. However, no evident improvement of permeation was observed in the case of IP, which had high LP solubility. It was suggested that HSL showed no enhancing effect, but solubilized IM, KP or FP, leading to high permeation from the gel. After 3 months' storage, the permeation rate did not change for 0.5% IM in 15% HSL gel, but decreased for 1% IM in 15% HSL gel. This indicates that in the case of 1% IM in 15% HSL gel, IM is in a supersaturated state immediately after preparation and then recrystallizes with time.
Henmi
T
T
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Fujii
M
M
Kikuchi
K
K
Yamanobe
N
N
Matsumoto
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D009823:Ointment Bases / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D051381:Rats; D012869:Skin Absorption; D013025:Glycine max / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009823:Ointment Bases; D010743:Phospholipids