Non-traditional application of drug and excipient

During formulation development, there are cases when, serendipitously, drug or excipients play a different role than intended one or a dual role. One of the examples of a non-traditional role is of a drug acting as a plasticizer. Plasticization tendency of APIs on polymers can be advantageous for hot melt extrusion, and film coating application. Due to the inherent plasticizing property of API, it can be mixed uniformly with other polymers using a V-blender or high shear mixer without the use of additional organic solvents during the formulation process. Divalproex sodium (DVS) is shown to possess plasticization tendency on Ethylcellulose(EC) using thermal, mechanical and rheological characterization of films of DVS and EC. Also, further characterization of the films using polarized microscopy, TGA, FTIR, Raman spectroscopy revealed the physical nature of the drug and polymer along with their interactions. The plasticization tendency was attributed to the presence of valproic acid, which is a component that is bound by coordinate bond with sodium valproate to form DVS. This study shows the non-traditional role of API as a plasticizer for a polymer (EC).

Some polymers can play a non-traditional role or dual role in formulation development; for example-a surfactant(poloxamer) can be used as plasticizer in hot melt extrusion, while Sodium Lauryl Sulfate, a wetting agent, can act as lubricant in a tablet formulation. Compression property of a sustained release polymer can aid the formulation scientist since it can be used alone or with less amount of compression aid to formulate a direct compression immediate release tablet or sustained release tablet dosage form. Affinisol® HPMC HME polymers were developed by Dow Chemicals to cater the need of Formulation Scientist for a low Tg HPMC for HME applications since the traditionally available grades have HPMC have much higher Tg and require the addition of plasticizer. Due to the low Tg of Affinisol® HPMC HME polymers, it is proposed that it may possess better compactability at low compression pressure. The study was undertaken to evaluate the compaction property of these polymers. Furthermore, powder properties were also examined for its proposed use as a dry binder or a direct compression sustained release polymer. Based on the compaction and powder properties of these polymers, these polymers can be used for the potential application as a dry binder or a direct compression sustained release polymer in tablet formulations.

Download full dissertation here: etd-2018-9051-1.pdf