Gastroresistant microparticles containing sodium alendronate prevent the bone loss in ovariectomized rats.
Sodium alendronate, an antiresorptive drug, primarily used in the treatment of osteoporosis was encapsulated in blended microparticles composed of Eudragit S100 and Methocel K15M. The micropowder obtained by spray-drying technique was characterized in terms of its morphology, particle size, encapsulation efficiency and in vitro drug release. In vivo studies were carried out in order to evaluate the pharmacodynamic effect and the ulcerogenic activity of sodium alendronate-loaded microparticles after oral administration in rats. Drug encapsulation efficiency was close to 80% and particle mean diameter of 13.8 microm. SEM analysis showed spherical collapsed shape particles with smooth surface. At pH 1.2, in vitro experiments showed that <10% of the drug was released from the microparticles. At pH 6.8, the microparticles were able to prolong the sodium alendronate release for 12h. In vivo experiments carried out in ovariectomized rats showed bone mineral density significantly higher for the sodium alendronate-loaded microparticles than for the negative control groups. Furthermore, the microencapsulation of the drug showed a significant reduction in the ulcerative lesion index. In conclusion, the blended microparticles are excellent oral carriers for sodium alendronate since they were able to maintain the drug antiresorptive effect and to reduce the gastrointestinal drug toxicity.
Cruz
Letícia
L
Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Assumpção
Evelise
E
Andrade
Sérgio F
SF
Conrado
Daniela J
DJ
Kulkamp
Irene C
IC
Guterres
Sílvia S
SS
Pohlmann
Adriana R
AR
D019386:Alendronate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001862:Bone Resorption / Q000517:prevention & control*; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D008863:Microspheres; D010052:Ovariectomy; D010316:Particle Size; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced; D013499:Surface Properties
D050071:Bone Density Conservation Agents; D004337:Drug Carriers; D011108:Polymers; D019386:Alendronate