title: Model drug as pore former for controlled release of water-soluble metoprolol succinate from ethylcellulose-coated pellets without lag phase: opportunities and challenges.
abstract: The objective of the present study was to evaluate the feasibility of using model drug metoprolol succinate (MS) as a pore former to modify the initial lag phase (i.e., a slow or non-release phase in the first 1-2 h) associated with the drug release from coated pellets. MS-layered cores with high drug-layering efficiency (97% w/w) were first prepared by spraying a highly concentrated drug aqueous solution (60% w/w, 70°C) on non-pareils without using other binders. The presence of MS in ethylcellulose (EC) coating solution significantly improved the coating process by reducing pellets sticking, which often occurs during organic coating. There may be a maximum physical compatibility of MS with EC, and the physical state of the drug in the functional coating layer of EC/MS (80:20) was simultaneously crystalline and non-crystalline (amorphous or solid molecule solution). The lag phase associated with hydroxypropylcellulose (HPC) as a pore former was not observed when MS was used as a pore former. The drug release from EC/MS-coated pellets was pH independent, inversely proportional to the coating levels, and directly related to the pore former levels. The functional coating layer with MS as a pore former was not completely stabilized without curing. Curing at 60°C for 1 day could substantially improve the stability of EC/MS-coated pellets. The physical state of the drug in the free film of EC/MS (85:15) changed partially from amorphous to crystal when cured at 60°C for 1 day, which should be attributed to the incompatibility of the drug with EC.
authors.affiliation: Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, No. 27, Taiping Road, Haidian District, Beijing, 100850, People's Republic of China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Wang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Dai
authors.forename: Xinyi
authors.initials: X
authors.lastname: Chang
authors.forename: Meiyan
authors.initials: M
authors.lastname: Yang
authors.forename: Ruifang
authors.initials: R
authors.lastname: Shen
authors.forename: Li
authors.initials: L
authors.lastname: Shan
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Gao
mesh_terms: D065966:Absorption, Physicochemical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D004343:Drug Implants / Q000008:administration & dosage / Q000138:chemical synthesis*; D006244:Hardness; D008790:Metoprolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D010316:Particle Size; D044367:Phase Transition; D016062:Porosity; D012995:Solubility; D013499:Surface Properties; D014867:Water / Q000737:chemistry*
chemical_list: D000319:Adrenergic beta-Antagonists; D020099:Coated Materials, Biocompatible; D004343:Drug Implants; D014867:Water; C013517:ethyl cellulose; D002482:Cellulose; D008790:Metoprolol