My product Flashcards
(33 cards)
Daprodustat CQAs
Description – exhaust air temp IPC = crushing strength and appearance checks
Identity – Input IR and end product testing
Impurities – Input material imps
Drug substance content – premix feed ratio, EG qty, mean weight
UDU – pre-mix blending, premix feed ratio, EG qty, individual core weight
Dissolution – liquid / solid ratio
Daprodustat CPPs
Pre mix blend speed and time
Api and excipient pre mix mass flow
Liquid mass flow
EG qty
Exhaust air temp
Daprodustat formulation
Daprodustat
Mannitol
Microcrystalline Cellulose (avicel)
Hypromellose
Croscarmellose Sodium
Colloidal Silicone Dioxide
Magnesium Stearate
Aquarius
Daprodustat excipient function
Mannitol Diluent
Microcrystalline Cellulose (avicel) Diluent
Hypromellose Binder
Croscarmellose Sodium Disintegrant
Colloidal Silicone Dioxide Glidant
Magnesium Stearate Lubricant
Aquarius Film-Coat
Daprodustat contraindications
Gemfibrozil - used to lower triglycerides when can’t take statins. It has the potential to increase the effectiveness of daprodustat so you make more red blood cells than intended = danger
Rifampicin - an antibiotic used to treat serious infections including tuberculosis. It has the potential to decrease the effectiveness of daprodustat
Why are things contraindicated with daprodustat?
Daprodustat is primarily metabolized by CYP2C8, a liver enzyme. This means that drugs that are CYP2C8 inhibitors can potentially increase the levels of daprodustat in the blood, while CYP2C8 inducers could decrease daprodustat levels. Strong CYP2C8 inhibitors, like gemfibrozil, are contraindicated with daprodustat, while moderate inhibitors may require dose adjustments. Daprodustat also inhibits CYP2C8, which could affect the metabolism of other drugs that are CYP2C8 substrates
Daprodustat – what to tell the dr about
Tell Dr if you have high blood pressure or cancer (may cause tumour to grow)
CKD and daprodustat may increase heart problems.
Daprodustat side effects
heart attack,
stroke
blood clots - blood clot in vein - deep vein thrombosis, blood clot in lung - pulmonary embolism, blood clot in dialysis access.
high blood pressure
skin rash, swelling, tummy pain, constipation.
Need to increase dose slowly as don’t want heam spike - this is dangerous. So also precautions about if you miss a dose.
Daprodustat – how does it work
Daprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor HIF-PHI
Prolyl hydroxylase catalyses the incorporation of oxygen into organic substrates. Thus in normic conditions, the prolyl hydroxylase catalyses the addition of oxygen (in the form of OH) onto HIF a which is subsequently broken down into peptides I.e. under normoxia, HIFα is hydrolysed by prolyl hydroxylase enzymes.
By binding to the prolyl hydroxylase, there’s no hydroxide addition to HIF α so it passes into the nucleus and joins with HIF β in the nucleus which induces the expression of target genes. It binds the hypoxia response elements of the genes, increasing gene transcription and therefore producing EPO.
Daprodustat – brand names
Jesduvroq and duvroq
Daprodustat primary process
Why are Gemfibrozil and rifampicin affected by daprodustat
Daprodustat is primarily metabolized by CYP2C8, a liver enzyme. This means that drugs that are CYP2C8 inhibitors can potentially increase the levels of daprodustat in the blood, while CYP2C8 inducers could decrease daprodustat levels.
Strong CYP2C8 inhibitors, like gemfibrozil, are contraindicated with daprodustat, while moderate inhibitors may require dose adjustments.
Daprodustat also inhibits CYP2C8, which rifampicin induces, reducing the effect of the rifampicin.
Dolutegravir CQAs
Description – exhaust air temp and spray rate. 49 deg C 200 g/min. IPC = crushing strength and appearance checks
Identity – Input IR and end product testing
Impurities – Input material imps
Drug substance content – API purity, main compression force, mean and individual weight
UDU – pre-mix blending, premix feed ratio, EG qty, individual core weight
Dissolution – water amount, wet massing time, main compression force, mean tablet hardness.
Dolutegravir CPPs
API purity IMQC test)
water addition, wet massing time.
main compression force
mean tablet hardness
mean and individual weight
UDU – pre-mix blending, premix feed ratio, EG qty, individual core weight
exhaust air temp and spray rate. 49 deg C 200 g/min.
Doli – which unit ops have impact but no CPPs?
Granulation – Content and UDU
Compression - Description
Dolutegravir formulation
Dolutegravir sodium
Mannitol
Microcrystalline cellulose,
Povidone (K29/32)
Sodium starch glycolate
Sodium stearyl fumarate.
Coat – Opadry II
Polyvinyl alcohol-partially hydrolyzed
Titanium dioxide
Macrogol
Talc
Iron oxide yellow (E172) (for 25 mg and 50 mg tablets).
Dolutegravir excipient function
Mannitol – diluent
Microcrystaline cellulose (avicel) – diluent
Povidone – binder
Sodium Starch Glycolate – disintegrant
Sodium stearyl fumarate – lubricant
The rest – film coat
Dolutegravir contraindications
Hypersensitivity to the active substance or to any of the excipients.
Co-administration with dofetilide.
Dolutegravir side effects
Allergic reactions such as skin rash, fever, fatigue, swelling and muscle or joint aches.
Headache, diarrhoea and nausea.
Itching, being sick, stomach pain/discomfort, insomnia, dizziness, depression anxiety etc
Dolutegravir – how does it work
Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral Deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle.
It reduces the amount of virus in your body and keeps low level, it also increases the number of CD4 cells in your blood.
Dolutegravir – brand names
Tivicay 10 mg, 25 mg and 50 mg
Dolutegravir primary process
Dolutegravir secondary process
- Dispensing API’s
- Initial mixing/blending with excipients
- Granulation
- Screen Wet Milling
- Drying
- Screen
- Blend (add SSG & SSF)
- Compression
- Coating
- Packaging
Dolutegravir – how classified
Integrase inhibitors (INIs) (Anti-retroviral medicines)
