Properties of melt extruded enteric matrix pellets.
The objective of this study was to investigate the properties of enteric matrix pellets that were prepared by hot-melt extrusion in a one-step, continuous process. Five polymers (Eudragit) L100-55, L100 and S100, Aqoat grades LF and HF) were investigated as possible matrix formers, and pellets prepared with Eudragit S100 demonstrated superior gastric protection and acceptable processibility. Extruded pellets containing Eudragit S100 and up to 40% theophylline released less than 10% drug over 2h in acid, however, the processibility and yields were compromised by the high amounts of the non-melting drug material in the formulation. Efficient plasticization of Eudragit S100 was necessary to reduce the polymer's glass transition temperature and melt viscosity. Five compounds including triethyl citrate, methylparaben, polyethylene glycol 8000, citric acid monohydrate and acetyltributyl citrate were investigated in terms of plasticization efficiency and preservation of the delayed drug release properties. The aqueous solubility of the plasticizer and its plasticization efficiency impacted the drug release rate from the matrix pellets. The use of water-soluble plasticizers resulted in a loss of gastric protection, whereas low drug release rates in acid were found for pellets containing insoluble plasticizers or no plasticizer, independent of the extent of Eudragit S100 plasticization. The release rate of theophylline in buffer pH 7.4 was faster for pellets that were prepared with efficient plasticizers. The microstructure and solid-state properties of plasticized pellets were further investigated by scanning electron microscopy and powder X-ray diffraction. Pellets prepared with efficient plasticizers (TEC, methylparaben, PEG 8000) exhibited matrices of low porosity, and the drug was homogeneously dispersed in its original polymorphic form. Pellets containing ATBC or citric acid monohydrate had to be extruded at elevated temperature and showed physical instabilities in the form of recrystallization at room temperature. Enteric matrix pellets with a diameter below 1mm and containing 30% theophylline could be successfully prepared by hot-melt extrusion when Eudragit S100 plasticized with either TEC or methylparaben was employed as the matrix material.
Schilling
Sandra U
SU
Drug Dynamics Institute, University of Texas at Austin, Austin, USA. sschilling@mail.utexas.edu
Shah
Navnit H
NH
Waseem Malick
A
A
McGinity
James W
JW
D003460:Crystallization; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods*; D004343:Drug Implants / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D010316:Particle Size; D010968:Plasticizers / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013806:Theophylline / Q000737:chemistry / Q000493:pharmacokinetics; D044366:Transition Temperature; D014783:Viscosity
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D010968:Plasticizers; D011108:Polymers; D013806:Theophylline