Dutasteride Tablet Bioavailability?

[docpepper]

What's up fellas.

I may have fucked up and ordered a few year's supply of a very low-bioavailability form of Dutasteride.

So Duasteride is a super lipophilic (fat-loving) molecule. That's why all 25 FDA-approved formulations of the drug are in capsule form, with the drug dissolved in oil inside the capsule.

I recently decided to switch from Finasteride to Dutasteride, so I threw in a bulk order of Healing Pharma Dutasteride tablets into my recent Indian Pharma order. It wasn't until a few weeks later did I figure out why the tablet form of the drug is so rare. I did some searching and found this study that compared Dutasteride softgel capsules to hard tablets. It found that the tablets had 76% bioavailability of the softgels. Not too bad, good enough for me.

Impact of Formulation on the Pharmacokinetics of Dutasteride: Results from Two Phase I Studies - PubMed

The bioavailability of, and peak exposure to, dutasteride are influenced by the formulation of the administered medication. These studies demonstrate the importance of formulation for obtaining the optimal pharmacokinetic properties of dutasteride.

pubmed.ncbi.nlm.nih.gov

But today I was trying to learn about something to do with lipophilic drug formulations and it reminded me of the Dutasteride tablets. I was thinking, what are the odds that this ostensibly very low-margin, relatively unknown Indian Pharma brand (Healing Pharma) is using the correct excipients to ensure that it's bioavailable in a tablet? After all, the tablets measured in the study linked above were an alternate formulation made by GSK when they were developing Avodart. Now, I imagine that a company like Healing that makes as many products as it does could probably figure it out, I'm a complete noob to pharmacology, but it doesn't seem like some rocket science thing to figure out. But I would have no idea. I could be taking what is in effect sugar pills everyday while slowly being kidnapped by the Norwood reaper for all I know.

So I tried a redneck experiment. I took two Dutasteride tablets, dropped one in water, and the other in olive oil. Within minutes, the tablet dropped in water lost all of its shape and turned into clumps of powder, and the tablet dropped in oil look pretty much unchanged. What does this tell me? I have no idea. Maybe someone here would know something about this.

I'm thinking I should probably just take the loss and buy some damn capsules to ensure I'm actually getting the drug. But I figured this is something someone like @Ghoul might have some insight on.

Would appreciate any insights you guys have.

 

[Ghoul]

What's up fellas.

I may have fucked up and ordered a few year's supply of a very low-bioavailability form of Dutasteride.

So Duasteride is a super lipophilic (fat-loving) molecule. That's why all 25 FDA-approved formulations of the drug are in capsule form, with the drug dissolved in oil inside the capsule.

I recently decided to switch from Finasteride to Dutasteride, so I threw in a bulk order of Healing Pharma Dutasteride tablets into my recent Indian Pharma order. It wasn't until a few weeks later did I figure out why the tablet form of the drug is so rare. I did some searching and found this study that compared Dutasteride softgel capsules to hard tablets. It found that the tablets had 76% bioavailability of the softgels. Not too bad, good enough for me.

Impact of Formulation on the Pharmacokinetics of Dutasteride: Results from Two Phase I Studies - PubMed

The bioavailability of, and peak exposure to, dutasteride are influenced by the formulation of the administered medication. These studies demonstrate the importance of formulation for obtaining the optimal pharmacokinetic properties of dutasteride.

pubmed.ncbi.nlm.nih.gov

But today I was trying to learn about something to do with lipophilic drug formulations and it reminded me of the Dutasteride tablets. I was thinking, what are the odds that this ostensibly very low-margin, relatively unknown Indian Pharma brand (Healing Pharma) is using the correct excipients to ensure that it's bioavailable in a tablet? After all, the tablets measured in the study linked above were an alternate formulation made by GSK when they were developing Avodart. Now, I imagine that a company like Healing that makes as many products as it does could probably figure it out, I'm a complete noob to pharmacology, but it doesn't seem like some rocket science thing to figure out. But I would have no idea. I could be taking what is in effect sugar pills everyday while slowly being kidnapped by the Norwood reaper for all I know.

So I tried a redneck experiment. I took two Dutasteride tablets, dropped one in water, and the other in olive oil. Within minutes, the tablet dropped in water lost all of its shape and turned into clumps of powder, and the tablet dropped in oil look pretty much unchanged. What does this tell me? I have no idea. Maybe someone here would know something about this.

I'm thinking I should probably just take the loss and buy some damn capsules to ensure I'm actually getting the drug. But I figured this is something someone like @Ghoul might have some insight on.

Would appreciate any insights you guys have.

Great work on that research and coming up with that question. I picked up where you left off, and the TLDR is there are several reputable manufacturers in India producing the tablet form.

India is a major source of the dutasteride API for other manufacturers worldwide. Clearly an ingredient they have expertise in, and they produce the most desirable form, "Dutasteride crystalline 2".

Several cheap excipients can now make it bioequivalent to the more expensive to produce gelcaps, like simply using cyclodextrin, a cheap excipient, as an absorption enhancer.

So why wouldn't the cheaper to produce, more stable tablets be available in the US?

Because the original FDA approved name brand, Avodart was developed and approved in gelcap form. The earliest synthesis of dutasteride was in a far more
crude, difficult to absorb form, so Avodart had to be formulated that way. Avodart costs $1300 for 30 gelcaps. Generic Dutasteride gelcaps $8. This is a likely a 1¢ per gelcap profit drug for generic manufacturers.

Now that it's a low priced generic. despite advances making the active ingredient easy to process into a bioequivalent solid tablet, that would require an expensive FDA reapproval process, rather than just copying the existing approved formulation. Generics sticking to the original drug form can use a relatively fast and inexpensive ANDA, Abbreviated New Drug Approval, process to put their product on the market.

There's not enough money to be made on generic dutasteride to justify the expense of getting a full new drug approval in the US, likely million of dollars.

In fact, Healing Pharma subcontracts it to Kivi Pharma to produce, because they have the necessary expertise to manufacture the tablet form, which is approved in India (they have a much less expensive process to demonstrate bioequivalency, though no reason to believe it's not as credible as the FDA's).

If they were just throwing the API together with random excipients, they could do that themselves very cheaply, and not involve another speciality manufacturer.
.

Formulation of a film-coated dutasteride tablet bioequivalent to a soft gelatin capsule (Avodart®): Effect of γ-cyclodextrin and solubilizers - PMC

The aim of this study was to optimize a tablet formulation of dutasteride that is bioequivalent to a commercially available soft gelatin capsule (Avodart®). The effect of cyclodextrin on enhancing the aqueous solubility of dutasteride was ...

pmc.ncbi.nlm.nih.gov

 

[docpepper]

Great work on that research and coming up with that question. I picked up where you left off, and the TLDR is there are several reputable manufacturers in India producing the tablet form.

India is a major source of the dutasteride API for other manufacturers worldwide. Clearly an ingredient that have expertise in, and they produce the most desirable form, "Dutasteride crystalline 2".

Several cheap excipients can now make it bioequivalent to the more expensive to produce gelcaps, like simply using cyclodextrin, a cheap excipient, as an absorption enhancer.

So why wouldn't the cheaper to produce, more stable tablets be available in the US?

Because the original FDA approved name brand, Avodart was developed and approved in gelcap form. The earliest synthesis of dutasteride was in a far more
crude, difficult to absorb form, so Avodart had to be formulated that way.

Now that it's a low priced generic. despite advances making the active ingredient easy to process into a bioequivalent solid tablet, that would require an expensive FDA reapproval process, rather than just copying the existing approved formulation.

There's not enough money to be made on generic dutasteride to justify the expense of getting that approval in the US, likely million of dollars.

In fact, Healing Pharma subcontracts it to Kivi Pharma to produce, because they have the necessary expertise to manufacture the tablet form, which is approved in India (they have a much less expensive process to demonstrate bioequivalency, though no reason to believe it's not as credible as the FDA's).

If they were just throwing the API together with random excipients, they could do that themselves very cheaply, and not involve another speciality manufacturer.
.

Formulation of a film-coated dutasteride tablet bioequivalent to a soft gelatin capsule (Avodart®): Effect of γ-cyclodextrin and solubilizers - PMC

The aim of this study was to optimize a tablet formulation of dutasteride that is bioequivalent to a commercially available soft gelatin capsule (Avodart®). The effect of cyclodextrin on enhancing the aqueous solubility of dutasteride was ...

pmc.ncbi.nlm.nih.gov

Ah man, great answer!

So it's just like MCT carriers for test I guess. Who the fuck is gonna spend tens of millions on clinical trials just for a less viscus oil, or in this case, for a different formulation which would have no practical impact on anyone's life and at best would have slightly-worse bioavailability than the standard formulation.

I found some COAs for the product I use, Dutaheal here:

Product Code - Healing Pharma India Pvt Ltd

Product Code

www.healingpharma.in

If you're interested in reading them yourself, just click "Batch Certificate" and type in "AGT 40449," or "AGT 4" to see a list of different batch certificates.

What's cool is you can see testing for your batch. Don't know what assay they're using, and it's their contract manufacturer doing the tests, so obvious conflict of interest, but still cool to read.

Unfortunately there's no information on the excipients used. Cool nonetheless.

I actually downloaded the entire 2022 Indian Pharmacopeia manual to see if there was any information on Dutasteride tablets and the excipients used, but no dice there.

Seems that besides the big pharma brands in India like Cipla and Sun Pharma, most Indian Dut formulations are tabs. Scanned some forums and found a lot of Indians saying the tabs were effective for them.

As per your comments RE: Healing and their 3rd party partner, they use Alventa now, at least for Dut. Very good point on this front, as Healing does manufacture some of their drugs themselves like Finasteride, Minoxidil, Raloxifene, but farm out presumably more annoying-to-produce stuff like Dutasteride, Omeprazole, and Anastrozole.

Fun little rabbit hole I went down on here.

 

[Ghoul]

Ah man, great answer!

So it's just like MCT carriers for test I guess. Who the fuck is gonna spend tens of millions on clinical trials just for a less viscus oil, or in this case, for a different formulation which would have no practical impact on anyone's life and at best would have slightly-worse bioavailability than the standard formulation.

I found some COAs for the product I use, Dutaheal here:

Product Code - Healing Pharma India Pvt Ltd

Product Code

www.healingpharma.in

If you're interested in reading them yourself, just click "Batch Certificate" and type in "AGT 40449," or "AGT 4" to see a list of different batch certificates.

What's cool is you can see testing for your batch. Don't know what assay they're using, and it's their contract manufacturer doing the tests, so obvious conflict of interest, but still cool to read.

Unfortunately there's no information on the excipients used. Cool nonetheless.

I actually downloaded the entire 2022 Indian Pharmacopeia manual to see if there was any information on Dutasteride tablets and the excipients used, but no dice there.

Seems that besides the big pharma brands in India like Cipla and Sun Pharma, most Indian Dut formulations are tabs. Scanned some forums and found a lot of Indians saying the tabs were effective for them.

As per your comments RE: Healing and their 3rd party partner, they use Alventa now, at least for Dut. Very good point on this front, as Healing does manufacture some of their drugs themselves like Finasteride, Minoxidil, Raloxifene, but farm out presumably more annoying-to-produce stuff like Dutasteride, Omeprazole, and Anastrozole.

Fun little rabbit hole I went down on here.

Obviously we'd love a full list of excipients, to be certain, but I presume they're keeping them as trade secrets.

Perhaps more importantly, in the absence of absolute certain proof (which is rarely found in anything related to medicine), is the element of overall trust one has in a manufacturer.

We know Sun, for instance is reliable, largely an effect of being a major exporter of generics having to meet foreign standards.

But I'll say that to my surprise, Healing Pharma seems to be right up there based on my experience with numerous products from them. It's even my preferred brand these days. You can see the attention to detail in pill production and packaging. That alone is no guarantee, but it is indicative of the effort they put into manufacturing. A wide range of pill forms, sizes, shapes, even more expensive to manufacture "split colors" for combination pills, despite being really cheap meds, does say something about them, and the fact they're making unique formulations specific to each API. The "shiny" finish on pressed tabs vs crumbly is another difference between manufacturers. It takes care to determine the correct ingredients and processes to achieve that. Compare that to a UGL (or bottom of the barrel India pharma) where every tab is the same sized chaulky white pill, using the same excipients.

 

[docpepper]

Obviously we'd love a full list of excipients, to be certain, but I presume they're keeping them as trade secrets.

Perhaps more importantly, in the absence of absolute certain proof (which is rarely found in anything related to medicine), is the element of overall trust one has in a manufacturer.

We know Sun, for instance is reliable, largely an effect of being a major exporter of generics having to meet foreign standards.

But I'll say that to my surprise, Healing Pharma seems to be right up there based on my experience with numerous products from them. It's even my preferred brand these days. You can see the attention to detail in pill production and packaging. That alone is no guarantee, but it is indicative of the effort they put into manufacturing. A wide range of pill forms, sizes, shapes, even more expensive to manufacture "split colors" for combination pills, despite being really cheap meds, does say something about them, and the fact they're making unique formulations specific to each API. The "shiny" finish on pressed tabs vs crumbly is another difference between manufacturers. It takes care to determine the correct ingredients and processes to achieve that. Compare that to a UGL (or bottom of the barrel India pharma) where every tab is the same sized chaulky white pill, using the same excipients.

I always love the Healing packaging. Feel like Patrick Bateman looking at business cards when I feel those shiny raised letters on the box, the texture, etc.

Seems a lot of the forum vets here are fans of Healing as well, they've become my go-to for that reason. Spiff just posted a bunch of tests, some of Healing products, and they all came back spot-on. And despite my initial skepticism at their prices, your posts praising them made me pull the trigger on a bunch of stuff and everything has worked out great. It's just this formulation that has me raising questions. It's probably fine, though, based off the digging we've done in this thread.

The lab package I get from Private MD Labs has PSA in there, so I'll be able to see the efficacy of these Dut tabs if my PSA starts going up over the next couple labs, compared to where it was on Finasteride.

Thanks for your digging on this matter bro. Appreciate it.