Sofosbuvir and Daclatasvir are BCS class I drugs. What that means is that they are highly soluble in water and get into the body easily.
Ledipasvir, Velpatasvir and Simeprevir are all essentially insoluble BCS class II drugs. This does not make them unusable (70% of all our drugs are like this) but it does mean there is more too it than simply ingesting them.
www.sciencedirect.com/science/article/pii/S1818087614000348
One technique to make insoluble drugs dissolve and get into the body is to change them. With simeprevir it is made into a sodium salt to aid solubility, however with simeprevir there is another issue: related substance C. This report is partially redacted but what you can see is that the originator had to apply for an exemption to allow more than the usual maximum quantity of impurity to be present and furthermore that this impurity is known to be toxic.
www.pmda.go.jp/files/000153596.pdf
With ledipasvir and velpatasvir they need to effectively be ground extremely finely so that there is a very large surface area to dissolve. There are a variety of ways to achieve this goal, but nevertheless it must be done. Micron size grinding - to 1 um is one approach and as you may have read from the article above there are many others. The goal is to make the API as small as possible. We used micronisation and the SVR rates we've seen provide reassurance that has been effective.
I have it on good authority that generic Sof+Vel will be available within 30 days so suggest anyone contemplating its use get something that has been formulated by experts - in other words don't try this particular trick at home.
