Influence of Different Meltable Binders on the Solid-State Behaviour and Dissolution Profiles of Solid Lipid Extrudates Processed Via Continuous Hot Melt Granulation

Abstract

Mere similar grades of same excipients manufactured by two different manufacturers often differ significantly that they even have an impact on the variations in final product or dosage form. Solid lipids are one of the most available options as matrix former in sustained drug delivery. Due to their chemical and physical complexity, lipids may exhibit a complex behaviour (i.e. melting crystallization and polymorphism). The aim of this study was to evaluate the physical and chemical properties of two Glyceryl Monostearate (GMS) lipids (Geleol from Gattefosse and Capmul GMS 50K from Abitec Corp. USA) and how these properties may affect during melt granulation process for sustained release applications. Thermal processing was applied on GMS samples to understand the polymorphic nature and suitability as meltable binders. Niacin was used as model drug. A thorough evaluation of GMS samples and sustained release tablets was undertaken using analytical techniques such as differential scanning calorimetry (DSC), X-ray diffraction (XRD). Moreover, melt viscosity study assisted to apprehend the behaviour of GMS samples in hot melt extrusion processing. Surface morphology of the drug and extruded granules examined via SEM and AFM revealed high level of surface interaction and dense structure of drug inside lipid matrix. The DSC and XRD study confirmed that Geleol could not withstand the heat treatment applied during thecontinuous melt granulation processing. The shifting of stable β form to an unstable α form in Geleol was detected. In the contrary case, Capmul GMS 50K was able to withstand the heat treatment supported by the applied analytical techniques. Nonetheless,both GMS samples perform differently in final dosage form. This change in stable β form to an unstable α form affected dissolution profiles at 3 months storage in accelerated condition. This study helped to interpret the complex solid-state behaviour of solid lipid extrudates with different compositions, in order to the simply and outline a suitable formulation strategy for the development of lipid-based oral dosage forms.