In vitro and in vivo evaluation of mucoadhesive microspheres consisting of dextran derivatives and cellulose acetate butyrate.
The objective of this study was to evaluate mucoadhesive properties and gastrointestinal transit of microspheres made of oppositely charged dextran derivatives and cellulose acetate butyrate (CAB). The microspheres were prepared by emulsion solvent evaporation method. A reference microsphere was made of lactose instead of dextran derivatives. Microspheres with a diameter of 425-710 microm were examined for in vitro mucoadhesion by the everted sac method. The results indicated that the percentage of adherence to the rat small intestine was affected by the amount of dextran derivatives in the microspheres. After 1.5h, the adhering percent of the reference microspheres and the microspheres containing 50% of dextran derivatives were 34 and 74%, respectively. Then gastrointestinal transit after oral administration to rats was evaluated by counting the microspheres remaining in the stomach and small intestine. The microspheres containing 40% of dextran derivatives adhered to the stomach rather than the small intestine. Mathematical analysis revealed that the time required for 50% of microspheres to leave the stomach was 1.42h, three times longer than the reference. These findings suggest that the microsphere is a promising device as a multiple-unit mucoadhesive system.
Miyazaki
Yasunori
Y
Pharmaceutical Department, Tokyo Women's Medical University Daini Hospital, Nishiogu-2-1-10, Arakawa-ku, 116-8567, Tokyo, Japan. myph@dnh.twmu.ac.jp
Ogihara
Kanako
K
Yakou
Shigeru
S
Nagai
Tsuneji
T
Takayama
Kozo
K
D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D002482:Cellulose / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003637:DEAE-Dextran / Q000008:administration & dosage / Q000493:pharmacokinetics; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics; D003911:Dextrans / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D004339:Drug Compounding; D005746:Gastric Emptying; D005772:Gastrointestinal Transit; D066298:In Vitro Techniques; D007583:Jejunum / Q000502:physiology; D008297:Male; D008863:Microspheres; D008954:Models, Biological; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics
D003911:Dextrans; D004337:Drug Carriers; D002482:Cellulose; C014396:cellulose acetate-butyrate; D003637:DEAE-Dextran; D016264:Dextran Sulfate; D013806:Theophylline