title: Immediate release pellets with lipid binders obtained by solvent-free cold extrusion.
abstract: Lipid-based drug delivery systems have spread in their use in pharmaceutical drug development. This work focuses on the use of lipid binders as alternative non-toxic extrusion aid for pellet formulations. The preparation of immediate release pellets with solid lipid binders through a solvent-free cold extrusion/spheronisation process was investigated in this study. Various binary, ternary and quaternary mixtures of powdered lipids and the model drug sodium benzoate were investigated and compared to well-known wet extrusion binders like microcrystalline cellulose and kappa-carrageenan. The cold lipid extrusion process offers multiple advantages as it is suitable for thermal sensitive as well as for hygroscopic drugs, furthermore no drying process to evaporate the solvent is needed and the process is feasible for different extruder types. Some of the developed pellets showed favourable properties like spherical shape, narrow size distribution, a high drug load of 80% sodium benzoate and a drug release of more than 90% within 40 min. The stability of drug release, which can be problematic when using lipid excipients, was sufficient for some mixtures, as storage under elevated temperatures changed the release profiles only slightly and no formulation released less than 80% within the first 60 min. A formulation with a mixture of hard fat, glycerol distearate and glycerol trimyristate showed the best results, as pellets with a low aspect ratio, narrow size distribution and complete drug release were obtained. Using appropriate mixtures of acylglycerides it becomes possible to produce pharmaceutical pellets with immediate release characteristics by cold extrusion and subsequent spheronisation. Thus, lipids are very promising alternatives to commonly used extrusion/spheronisation binders.
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Krause
authors.forename: Markus
authors.initials: M
authors.lastname: Thommes
authors.forename: Jörg
authors.initials: J
authors.lastname: Breitkreutz
mesh_terms: D002351:Carrageenan / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D010316:Particle Size; D020160:Sodium Benzoate / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
chemical_list: D005079:Excipients; D008055:Lipids; D012997:Solvents; D002351:Carrageenan; D002482:Cellulose; D020160:Sodium Benzoate; C109691:microcrystalline cellulose