Solid Lipid Extrudates Research Articles

Controlled release of active as a consequence of the die diameter in solid lipid extrusion

The aim of the study was the investigation of dependency of the release profile on the original diameters of milled extrudates manufactured by solid lipid extrusion. Different die diameters in the range of 0.3 mm to 5.0 mm were used. The extrudates were milled and sieved. The fractions between 315 µm and 400 µm were investigated within their shape, surface area and dissolution profiles by using the dissolution tester and the disintegration tester for short-time dissolution tests. Different pH-media were used for the release tests: pH 1.2 to imitate release conditions in the stomach and pH 7.4 to imitate conditions in the mouth. The chosen active enrofloxacin, a derivate of 3-quinolinecarboxylic acid, offers different solubilities in these release media. Two conclusions of this study were obtained: In the case of slightly solubility of active in the medium there was no dependency of the released active on the die diameter. If the active was very slightly soluble in the release medium a dependency between the two parameters was found. Having bad tasting actives like enrofloxacin, this achievement has an enormous impact on the manufacturing processes: a reduction of die diameters and therefore reduction of released amount of active will lead to taste masking.

Understanding the solid-state behaviour of triglyceride solid lipid extrudates and its influence on dissolution

Three monoacid triglycerides differing in their fatty acid chain lengths were extruded below their melting temperatures. Physical characterization was conducted on the powders as well as the extrudates with a combination of DSC, XRPD and vibrational spectroscopy to get a deeper insight into the complex solid-state behaviour of lipids and solid lipid extrudates during processing and storage. The combination of extrusion temperature and friction was a key factor for the lipid polymorphic behaviour after extrusion. Polymorphic transitions had a strong influence on the dissolution behaviour due to crystallization of the stable β-form from the unstable α-form on the surface of the extrudate. These correlations help to understand the solid-state behaviour of lipids and to avoid process conditions which lead to unstable dosage forms. Tailor-made dissolution profiles for a model drug could be achieved using triglycerides of different fatty acid chain lengths as the dissolution rate is chain-length dependent. The solid-state form of the drug was unchanged after storage in accelerated conditions over 10 months. These studies demonstrate that although triglycerides are a promising basis for oral dosage forms, a good understanding and monitoring of the solid-state behaviour is mandatory to obtain reliable and reproducible dosage forms.

Influence of thermal and thermo-mechanical treatment

Two lipids with similar melting ranges but of different composition were analyzed using differential scanning calorimetry and X-ray diffraction. The lipids were processed via extrusion or were tempered at different temperatures; they were analyzed directly after extrusion and after storage at 40°C. Precirol ATO 5® showed high sensitivity to storage time and varied temperature exposure. Extrusion showed only marginal influences on the solid state. Melting peaks were narrower and shifted to higher temperatures in comparison to the untreated powder. Dynasan 114® was more robust, changes in the solid state could only be shown for samples treated above the melting range. Thus, Dynasan 114® is more appropriate for solid lipid extrusion of pharmaceutical products.

Solid lipid extrusion of sustained release dosage forms

The applicability of the solid lipid extrusion process as preparations method for sustained release dosage forms was investigated in this study. Two lipids with similar melting ranges but of different composition, glyceryl palmitostearate (Precirol ATO 5 ®) and glyceryl trimyristate (Dynasan 114 ®), and mixtures of each lipid with 50% or 75% theophylline were extruded at temperatures below their melting ranges. Extrudates were analyzed using differential scanning calorimetry, scanning electron microscopy, porosity measurements and in vitro drug dissolution studies. The possibility of processing lipids by softening instead of complete melting and without subsequent formation of low-melting, metastable polymorphs could be demonstrated. Extrudates based on formulations of glyceryl palmitostearate/theophylline (50:50) and glyceryl trimyristate/theophylline (50:50) showed sustained release properties. An influence of extrusion conditions on the matrix structure was shown for extrudates based on a mixture of glyceryl trimyristate and theophylline (50:50). Glyceryl trimyristate tended to solidify in porous structures after melting. Exceeding a material temperature of 50.5 °C led to porous extrudate matrices with a faster drug release. The production of novel, non porous sustained release matrices was possible at a material temperature of 49.5 °C. Extrudates based on glyceryl trimyristate/theophylline (50:50) only slight changes in melting enthalpy and stable drug release profiles.