title: Supersaturated controlled release matrix using amorphous dispersions of glipizide.
abstract: Spray dried dispersions (SDDs) of glipizide, a BCS Class II model drug, were prepared using various grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and copovidone S-630 as carriers. The SDDs appeared as a single amorphous phase with up to 60% drug loading level as revealed by X-ray powder diffraction (XRPD), modulated differential scanning calorimetry (mDSC) and scanning electron microscopy (SEM). Supersaturated micro-dissolution testing of various SDDs in fasted state simulated intestinal fluid showed prolonged supersaturation state (up to 180min) with solubility increases of 5.2-13.9 fold relative to crystalline drug under similar conditions. Solubility and stability characteristics of the most desirable SDDs in terms of relative dissolution AUCs (AUC(SDD)/AUC(crystalline)) and supersaturated concentration ratios (C180/Cmax) were determined. Results show that HPMCAS-based SDDs achieve a higher degree of supersaturation compared to Copovidone S-630 and that SDDs comprising HPMCAS-M and HPMCAS-H maintained stable supersaturated concentration. Dissolution data showed that SDD-loaded CR tablets provide stable supersaturated concentration within the hydrated matrix with increased rate and extent of drug dissolution over 24h. Co-existence of HPMCAS and HPMC within the hydrating matrix showed strong suppression of drug crystallization and allowed achievement of zero-order and slow-first order release kinetics.
authors: School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
authors: Zheng
authors: Z
authors: Lu
authors: Ashland Specialty Ingredients, 500 Hercules Road, Wilmington, DE 19808, USA.
authors: Yonglai
authors: Y
authors: Yang
authors: Ashland Specialty Ingredients, 500 Hercules Road, Wilmington, DE 19808, USA.
authors: Rae-Ann
authors: RA
authors: Covington
authors: Ashland Specialty Ingredients, 500 Hercules Road, Wilmington, DE 19808, USA.
authors: Yunxia Vivian
authors: YV
authors: Bi
authors: Ashland Specialty Ingredients, 500 Hercules Road, Wilmington, DE 19808, USA.
authors: Thomas
authors: T
authors: Dürig
authors: School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
authors: Marc A
authors: MA
authors: Ilies
authors: School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA. Electronic address: reza.fassihi@temple.edu.
authors: Reza
authors: R
authors: Fassihi
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000378:metabolism; D005913:Glipizide / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D005913:Glipizide
keywords: Amorphous solid dispersion; Controlled-release matrix tablet; Copovidone; Glipizide; Hydroxypropyl methylcellulose acetate succinate (HPMCAS); Spray drying