Influence of water uptake, gel network, and disintegration time on prednisone release from encapsulated solid dispersions.
Prednisone is considered the glucocorticoid of choice for anti-inflammatory and immunosuppressant effects. However, its very low aqueous solubility can compromise oral bioavailability. Changes in the dissolution of a prednisone-PEG 6000 solid dispersion into capsule were investigated by addition of pregelatinized starch. Physical state of prednisone:PEG 6000 was analyzed by X-ray diffractometry, and scanning electron microscopy. Capsule formulations containing prednisone-PEG 6000 and pregelatinized starch showed superior dissolution properties (> 95% in 60 min) when compared with reference capsules without disintegrant (< 45% in 60 min). Water uptake and disintegration time were directly correlated with pregelatinized starch amount. The morphology of prednisone-PEG 6000 particles with disintegrant was analyzed by SEM, showing a novel surface structure. Thus, solid dispersions of a poorly water soluble drug combined with a disintegrant were confirmed as a valid approach to the improvement of drug dissolution.
Leonardi
Darío
D
Area Tecnología Farmacéutica, Departamento Farmacia, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, IQUIR (CONICET), 2000, Rosario, Argentina.
Salomon
Claudio J
CJ
D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D005782:Gels; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols / Q000737:chemistry*; D011241:Prednisone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013213:Starch / Q000737:chemistry; D013997:Time Factors; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D002214:Capsules; D004337:Drug Carriers; D005079:Excipients; D005782:Gels; D005938:Glucocorticoids; D014867:Water; D011092:Polyethylene Glycols; D013213:Starch; D011241:Prednisone