Suppression of agglomeration in fluidized bed coating. IV. Effects of sodium citrate concentration on the suppression of particle agglomeration and the physical properties of HPMC film.
We previously reported that sodium citrate (Na citrate), which is a high order salt in the Hofmeister's series, greatly suppressed particle agglomeration in fluidized bed coating (Pharm. Res., 16 (1999), 1616-1620). In this paper, we studied the effects of Na citrate concentration on the particle agglomeration in fluidized bed coating and on the structure of coated film on the particles. Spherical granules made of crystalline cellulose (Celphere) containing phenacetin were coated in a fluidized bed with the aqueous coating solution of hydroxypropylmethyl cellulose (HPMC) containing Na citrate at various concentrations. The particle diameter and drug release profile of coated particles, and the physical properties, i.e. tensile strength, elongation percentage at break, porosity and pore size distribution, of the HPMC cast film were investigated. The particle agglomeration was suppressed with the increasing Na citrate concentration. It is considered that the increase in the suppression effect was caused by the salting-out effect of the increased Na citrate. In the HPMC cast film system, the tensile strength and elongation percentage decreased and the porosity and cumulative pore volume increased with an increase in Na citrate concentration. It is considered that the increase in the porosity by adding Na citrate resulted from a phase separation due to the salting-out during the film forming process. The drug release rate from coated particles also increased with the increasing Na citrate concentration. It can be concluded that the increase in the release rate was due to the increase in porosity of the HPMC coated film caused by the increased Na citrate concentration.
Laboratory of Medical and Pharmaceutical Technology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, 192-0392, Tokyo, Japan. tn96135@ps.toyaku.ac.jp
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D000465:Algorithms; D002951:Citrates / Q000737:chemistry*; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010232:Paraffin; D010316:Particle Size; D010615:Phenacetin / Q000737:chemistry; D016062:Porosity; D000077559:Sodium Citrate; D013718:Tensile Strength
D002951:Citrates; D005079:Excipients; D000077559:Sodium Citrate; D065347:Hypromellose Derivatives; D010232:Paraffin; D008747:Methylcellulose; D010615:Phenacetin