Fabrication and in vivo evaluation of highly pH-responsive acrylic microparticles for targeted gastrointestinal delivery.
Acrylic enteric microparticles for oral drug delivery were prepared by an oil-in-oil emulsion solvent evaporation process. The novel use of sorbitan sesquioleate as a surfactant produced Eudragit L55, L and S (pH thresholds of 5.5, 6 and 7, respectively) microparticles of good morphology (spherical, smooth surfaced), size (<100microm) and size uniformity. The process was efficient (yield approximately 90%) and the encapsulated model drug (prednisolone) was in the amorphous form. The Eudragit L and S microparticles showed excellent pH-responsive drug release in dissolution studies (negligible drug release at pH 1.2; rapid drug release above the polymers' pH thresholds). In contrast, Eudragit L55 particles aggregated in fluid and showed poor control of drug release. In vivo in rats, Eudragit L microparticles released their drug load rapidly (T(max)<1h) and the C(max) and AUC were higher than those of a control suspension of prednisolone. Drug absorption from Eudragit S microparticles was low which was attributed to the fact that the threshold pH of Eudragit S was not reached in the rat intestine and drug release was therefore incomplete. It was concluded that although the rat is an inappropriate model for the investigation of Eudragit S microparticles, the positive results seen with the Eudragit L microparticles indicate its potential use in pH-targeted drug delivery.
Kendall
Richard A
RA
Department of Pharmaceutics, School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom.
Alhnan
Mohamed A
MA
Nilkumhang
Suchada
S
Murdan
Sudaxshina
S
Basit
Abdul W
AW
D000179:Acrylates / Q000737:chemistry*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients; D041981:Gastrointestinal Tract; D006863:Hydrogen-Ion Concentration; D008297:Male; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D011109:Polymethacrylic Acids; D011239:Prednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013535:Suspensions; D014783:Viscosity; D014961:X-Ray Diffraction
D000179:Acrylates; D005079:Excipients; D011109:Polymethacrylic Acids; D013535:Suspensions; C038300:methylmethacrylate-methacrylic acid copolymer; D011239:Prednisolone