“Development of solvent-free techniques for tablet manufacturing”

Abstract

Aqueous and organic solvents are widely used during drug manufacturing processes, and they are used in large quantities mainly in kneading and in coating of tablets and granules. The use of different solvents during the manufacture of medicines has many drawbacks. Organic solvents (such as alcohol) have some environmental hazards due to their toxicity, flammability and the difficulty of disposal after drying. In addition, the time consumed due to solvent evaporation and drying is long and consumes energy which increases the cost of production. Water is one of the best solvents because it is safer, but there are many concerns when using it, such as increasing the time period due to drying, and the degradation of drugs sensitive to moisture or causing microbial contamination. Solvent-free technologies offer a practical solution to overcome these barriers. One of these techniques is hot melt granulation (HMG) which is defined as a technique in which a binder of relatively low melting point is molten to coat and agglomerate the powder particles yielding granules of larger particle size. The purpose of this research was to develop and evaluate this non-solvent-based technology during the manufacture of extended-release drug Divalproex sodium (DVS) used as antiepileptic, antimigraine, and in bipolar disorder treatment. The application of this technique (hot melt granulation) with lipid substances provided protection from moisture, while masking the bitter taste of the drug and most importantly extending the drug dissolution for a long time (about 24 hours). Quality by design (QbD) principles was applied to the HMG process to delineate the normal operating range (NOR) for the critical process and formulation parameters (CPP and CFP) (granulation time, impeller speed, and binder type/concentration). A quality target product profile (QTPP) for an extended dissolution tablet was achieved by selecting dissolution as a critical quality