Formulation development and scale-up of dutasteride liquisolid tablets.

Abstract

Introduction: Liquisolid (LS) technology is particularly advantageous for poorly water-soluble drugs administered in very low doses because of the improved dissolution rate and superior content uniformity. However, there is a lack of research papers describing the application of this concept on an industrial scale. Thus, we present trials conducted to develop tablets containing 0.5 mg of water-insoluble dutasteride according to the LS approach.

Methods: We divided the study into two stages: developing a placebo formulation and producing liquisolid tablets containing dutasteride on a pilot scale. We tested all the manufactured tablets for mass uniformity, resistance to crushing, disintegration time, dissolution, stability, and presence of impurities.

Results: We demonstrated that a standard high-shear granulator mixer with a spraying system is effective for LS formulation development and transfer to the pilot scale. We were able to compress the system into tablets with the desired assay, content uniformity, dissolution, and mechanical strength.

Conclusions: Multiple operations can be performed on one piece of equipment - that is, pre-mixing a carrier, wetting of the carrier with a solution of an active ingredient in a non-volatile liquid, mixing of the resulted mass with a coating agent, as well as additional excipients. Preparation of powder blends ready for tableting in line with the one-pot process approach is especially advantageous for the safety of staff engaged in the manufacturing of highly potent drug products.