Redispersible, dry emulsion of lovastatin protects against intestinal metabolism and improves bioavailability.
OBJECTIVE
To prepare a redispersible, dry emulsion (DE) and investigate whether it can improve intestinal stability and oral absorptive efficiency of the poorly water-soluble lovastatin (Lov).


METHODS
Phosal 53 MCT, Tween 80, and starch sodium octenyl succinate were employed as the oil phase, emulsifying agent, and matrix material, respectively. The redispersible, DE of Lov (Lov-DE) was prepared by spray drying the submicron emulsion of Lov. The characteristics of DE and the in vitro drug release were studied. The protective effects on the metabolism of Lov- DE and reference formulations, including the Lov suspension and the hydroxypropyl-beta-cyclodextrin (CD) complex were investigated in microsomes and the gut wall of male Sprague-Dawley (SD) rats. The bioavailability in SD rats was evaluated simultaneously.


RESULTS
Lov-DE in distilled water was reconstituted compared with the submicron emulsion of Lov before spray drying, and remained almost unchanged after 3 months' storage at room temperature. Compared with the Lov suspension, the in vitro Lov dissolution of both the redispersible, DE and CD complex increased obviously. Compared with control formulations, the metabolism studies carried out in vitro and in vivo confirmed that the redispersible, DE presented remarkable protective effects as indicated by the decreased metabolism rate of Lov. Lov-DE showed a 1.83-fold and 1.44-fold higher the area under the curve(AUC0-8 h)of Lov compared with that of the Lov suspension and CD complex in SD rats, respectively.


CONCLUSIONS
Lov-DE reduced the metabolism of Lov in the small intestine and improved its oral absorption in SD rats.
Ge
Zhen
Z
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Zhang
Xin-xin
XX
Gan
Li
L
Gan
Yong
Y
D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008148:Lovastatin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin