Home Forums Main Forum Experts Corner Compounding Why Formulation Matters (or does not)

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  • #25413
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    This is a bump for this post.

    Just a quick reminder to people that there is more to medication that just the purity of the API. For most medications formulation plays an important role in making them “bioavailable”. Bioavailable means that they can get into your body to do their work. If they don’t get in you might as well be swallowing sand.

    With good factory options available I suggest using those, but if you insist on using API please choose Sofosbuvir and Daclatasvir ONLY.

    Ledipasvir is far less forgiving and Velpatasvir will simply not be absorbed (it is BCS class IV – insoluble and impermeable). Voxilaprevir is likely to be just as problematic as Velpatasvir so while you might be able to source it, you would do far better to wait for a generic factory formulation.


    YMMV

    #25414
    Avatar photosplitdog
    • Guardian Angel
    • ★★★★★
    @splitdog

    “…..so while you might be able to source it, you would do far better to wait for a generic factory formulation.”

    I figured as much. Hopefully it is sooner than later. :P


    splitdog@roadrunner.com

    Genotype 3
    VL 4,100,000
    ALT 101 AST 71
    Treatment Naive
    Started Sof/Dac Jan 12, 2016
    VL= <15 4 weeks in. AST/ALT normal.
    VL=UNDETECTED 8 weeks in.
    SVR4= Virus back. 3,300,000

    Started generic Epclusa Sep. 23, 2017

    4 weeks in <15 *Detected.
    12 weeks in <15 *Not Detected.
    16 weeks in <15 *Not Detected.
    Finished 24 weeks treatment 3-17-18
    SVR5 <15 Not Detected.
    SVR 20 <15 Not Detected.
    SVR 44 <15 Not Detected.

    Thank you Jesus.
    Thank you Dr. James

    #25415
    Avatar photosplitdog
    • Guardian Angel
    • ★★★★★
    @splitdog

    Dr Freeman, does the weight (dose) of an existing drug get reduced if the solubility rises? Is there some kind of relationship to maintain the same bioavailability? I find this new particle technology fascinating.


    splitdog@roadrunner.com

    Genotype 3
    VL 4,100,000
    ALT 101 AST 71
    Treatment Naive
    Started Sof/Dac Jan 12, 2016
    VL= <15 4 weeks in. AST/ALT normal.
    VL=UNDETECTED 8 weeks in.
    SVR4= Virus back. 3,300,000

    Started generic Epclusa Sep. 23, 2017

    4 weeks in <15 *Detected.
    12 weeks in <15 *Not Detected.
    16 weeks in <15 *Not Detected.
    Finished 24 weeks treatment 3-17-18
    SVR5 <15 Not Detected.
    SVR 20 <15 Not Detected.
    SVR 44 <15 Not Detected.

    Thank you Jesus.
    Thank you Dr. James

    #25417
    dope-on-a-rope.jpgDr James
    • Guardian Angel
    • ★★★★★
    @fixhepc

    There are two baseline factors.

    • Water solubility.
    • Lipid membrane permeability.

    We need a drug to be water soluble to dissolve in the stomach.

    BUT

    We also need it to be fat (lipid) soluble to “float” through the gut lining and into the blood (unless there is a transporter it can hijack).

    You may notice that we want both water and fat soluble.

    Things that are say like salt or sugar dissolve easily in water, but ever tried to dissolve them in oil?

    Similarly things like chewing gum won’t dissolve in water, but will dissolve in oil (fast into orange oil gum remover for example).

    Given these two almost opposite requirements only about 30% of medications have this physical characteristic. Basically they have a polar (water loving) and non polar (lipid loving) part. Technically hydrophilic (water loving) and hydrophobic (water hating, oil loving) parts.

    In day to day life dish washing detergent and alcohol are two common things that have this dual nature.

    BCS class I chemicals are water soluble and permeable (detergant, alcohol)
    BCS class II chemicals are relatively insoluble but permeable (oily)
    BSC class III chemicals are soluble but relatively impermeable (salty)
    And BCS class IV chemicals a insoluble and impermeable (ie like sand or rock)

    Velpatasvir is BCS class IV.


    YMMV

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