Novel gelatin microcapsule with bioavailability enhancement of ibuprofen using spray-drying technique.
A poorly water-soluble ibuprofen and ethanol can be encapsulated in gelatin microcapsule by spray-drying technique. To develop a novel ibuprofen-loaded gelatin microcapsule with bioavailability enhancement, the effect of spray-drying conditions, gelatin, ibuprofen and sodium lauryl sulfate on the ibuprofen solubility and the amount of ethanol encapsulated in gelatin microcapsule were investigated. The ibuprofen solubility and amount of encapsulated ethanol increased as inlet temperature and amount of sodium lauryl sulfate increased, reached maximum at 105 degrees C and 0.6%, respectively and after that followed a rapid decrease. Furthermore, they abruptly increased as the amount of gelatin increased, reaching maximum at 4% then remaining almost stable, but the encapsulated ethanol content decreased noticeably. Likewise, the ibuprofen solubility increased as the amount of ibuprofen increased, reaching maximum at 0.5% and beyond that, there was no change in the solubility. However, the encapsulated ethanol content hardly changed irrespective of the amount of ibuprofen. Furthermore, the formula of ibuprofen-loaded gelatin microcapsule at the ratio of gelatin/ibuprofen/sodium lauryl sulfate/water/ethanol of 4/0.5/0.6/30/70 showed ibuprofen solubility of about 290microg/ml and ethanol content of about 160microg/mg. This gelatin microcapsule dramatically increased the initial dissolution rate of ibuprofen compared to ibuprofen powder in pH 1.2 simulated gastric fluid. Moreover, it gave significantly higher initial plasma concentrations, Cmax and AUC of ibuprofen in rats than did ibuprofen powder, indicating that the drug from gelatin microcapsule could be more orally absorbed in rats. Our results suggested that the enhanced oral bioavailability of ibuprofen in the gelatin microcapsule was contributed by the marked increase in the absorption rate of ibuprofen due to the crystallinity change to amorphous form and increase in dissolution rate of ibuprofen in the gelatin microcapsule in rats. Thus, the ibuprofen-loaded gelatin microcapsule developed using spray-drying technique with gelatin would be useful to deliver ibuprofen in a pattern that allows fast absorption in the initial phase, leading to better absorption.
Li
Dong Xun
DX
College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyongsan 712-749, South Korea.
Oh
Yu-Kyuong
YK
Lim
Soo-Jeong
SJ
Kim
Jong Oh
JO
Yang
Ho Joon
HJ
Sung
Jung Hoon
JH
Yong
Chul Soon
CS
Choi
Han-Gon
HG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002214:Capsules; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003890:Desiccation; D000431:Ethanol / Q000737:chemistry; D005079:Excipients; D005780:Gelatin / Q000737:chemistry*; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D005079:Excipients; D012997:Solvents; D000431:Ethanol; D005780:Gelatin; D007052:Ibuprofen