Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion

Eur J Pharm Biopharm. 2001 Sep;52(2):181-90. doi: 10.1016/s0939-6411(01)00162-x.

Abstract

The objective of the present study was to investigate the influence of formulation factors on the physical properties of hot-melt extruded granules and compressed tablets containing wax as a thermal binder/retarding agent, and to compare the properties of granules and tablets with those prepared by a high-shear melt granulation (MG) method. Powder blends containing phenylpropanolamine hydrochloride, Precirol and various excipients were extruded in a single-screw extruder at open-end discharge conditions. The extrudates were then passed through a 14-mesh screen to form granules. The extrusion conditions and the optimum amount of wax to function as the thermal binder were dependent on the properties of the filler excipients. At the same wax level, drug release from tablets decreased in the order of using microcrystalline cellulose (MCC), lactose and Emcompress as the filler excipient. The observed differences in the dissolution properties of the tablets were due to the differences in the solubility, swellability and density of the filler excipients. Replacing Precirol with Sterotex K, a higher melting point wax, resulted in slightly increased dissolution rates, when the extrusion was performed at the same temperature conditions. Hot-melt extruded granules were observed to be less spherical than high-shear melt granules and showed lower values of bulk/tap densities. However, tablets containing MCC or lactose granules prepared by hot-melt extrusion (HME) exhibited higher hardness values. Slower drug release rates were found for tablets containing MCC by HME compared with MG. Analysis of the hot-melt extruded granules showed better drug content uniformity among granules of different size ranges compared with high-shear melt granules, resulting in a more reproducible drug release from the corresponding tablets.

MeSH terms

  • Adrenergic alpha-Agonists / chemistry
  • Adrenergic alpha-Agonists / pharmacokinetics*
  • Chemistry, Pharmaceutical
  • Compressive Strength
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics
  • Hot Temperature
  • Particle Size
  • Phenylpropanolamine / chemistry
  • Phenylpropanolamine / pharmacokinetics*
  • Tablets
  • Waxes / chemistry
  • Waxes / pharmacokinetics

Substances

  • Adrenergic alpha-Agonists
  • Drug Carriers
  • Tablets
  • Waxes
  • Phenylpropanolamine