Drug product performance of newly innovated drugs under clinical trial phase three/Four. Amlodipine & Camsylate Esaxerenone 2.5 mg Pindolol (10mg) & Clopamide(5mg) Nebivolol(5mg)

1. Welcome To Our Presentation
Drug product performance of newly innovated drug under clinical trile phase three/Four
Group-G
Sadia Afrin Shanchita(977)
Md.Junnatul Fardos(979)
Al Fahad Ul Islam(981)
Mst. Rashna Sharmin(986)
Batch: 17th A
Department Of Pharmacy
Daffodil International University
Date: 13-10-2019

2. Agenda
Amlodipine & Camsylate
Esaxerenone 2.5 mg
Pindolol (10mg) & Clopamide(5mg)
Nebivolol(5mg)

3. Amlodipine & Camsylate
• Amlodipine is a dihydropyridine calcium antagonist, that inhibits the
transmembrane influx of calcium ions into vascular smooth muscle and cardiac
muscle.

4. Why this study?
This study was designed to determine the effectiveness and tolerability of
amlodipine camsylate compared with amlodipine besylate in Korean patients with
mild to moderate hypertension.
•Performance
• Hardness:4.9kg
• Friability:0.66%
• Weight variation:3.95%
• Disintegration Time:8 min
•Formulation
• Amlodipine Camsylate 15mg
(5.35%)
• Diluents: Starch 75.6%= 209mg
• Lubricants: Steric acid 4% =10.4mg
• Binder: cellulose 4%=10.4mg
• Disintegrates: Cross polyvinyl
pyrrolidine12%=31.2mg

5. Formulation Method

6. Pharmacokinetics
Amlodipine is well absorbed by the oral route with a mean oral
bioavailability around 60%;
The half-life of amlodipine is about 30 h to 50 h, and steady-state
plasma concentrations are achieved after 7 to 8 days of daily dosing.
In the blood it has high plasma protein binding of 97.5%.
It is slowly metabolized in the liver by CYP3A4
Renal elimination is the major route of excretion with about 60% of
an administered dose recovered in urine

7. Esaxerenone 2.5 mg
Esaxerenone (brand name Minnebro) is a nonsteroidal
antimineralocorticoid drug, developed by Daichi Sankyo
Company and is approved in Japan for the treatment of
hypertension. This drugs is used as adjunctive therapy, in
combination with other drugs, for the management of
chronic heart failure.

8. Why this study
• It is mineralocorticoid receptor blocker that show kidney
protective effects in preclinical studies, it is a potential therapy
to treat diabetic kidney disease.
• It is highly selective antagonist of the mineralocorticoid
receptor so that it has good safety profile and has no adverse
effect to sex hormones.
• This study determined the optimal doses for lowering blood
pressure in patients with essential hypertension.

9. Formulation
API- Esaxerenone(2%)- 2mg
Diluent- Starch(79%)- 127mg
Lubricant- Magnesium stearate(4%)- 6.4mg
Disintegrates- Cross carboxy methyl cellulose(12%)- 19.2mg
Binder- cellulose(3%)- 4.8mg
Performance
Hardness test – 4.4 kg
Disintegration time – 7 min
Wright variation – 6.3%
Friability test – 0.35%

10. Pharmacodynamics
• Act on mineralocorticoid receptors in kidney tubular epithelial cells
• Lower BP by inhibition of urinary Na+ reabsorption and potassium (K+)
excretion
• Binding of aldosterone to MR plays a central role in the regulation of plasma
sodium (Na+), extracellular potassium (K+) and regulate arterial blood
pressure, so by acting on this receptor esaxerenone give effect as
antihypertensive drug.
Pharmacokinetics
1.Esaxerenone gives rapid absorption.
2.Drug will distribute within the whole body through blood.
3.It cross multiple metabolism pathways including oxidation, glucuronidation,
and hydrolysis, the low contribution of transporters, indicated limited drug-
drug interaction.
4.It has a long elimination half‐life (~20 h). Low urinary excretion of
esaxerenone suggested that the plasma exposure of esaxerenone was not
affected by renal dysfunction.

11. Pindolol (10mg) &
Clopamide(5mg)
• Why This Study
Pindolol similar to propranolol with an extra
contraindication for hyperthyroidism. Pindolol has modest
beta-adrenergic agonist activity and is therefore used with
caution in angina pectoris. It has a negligible negative
inotropic effect on cardiac muscle.
The beta-adrenergic blocking agents
are being used with increasing
frequency in the treatment of
essential hypertension. Pindolol has
been proven effective in the
treatment of hypertension, both
alone and combined with
hydralazine. During work pindolol
decreases systolic blood pressure.
Clopamide has proven very suitable
as a hydralazine

12. Formulation Performance
• Hardness: 5.7 Kg
• Friability: 0.65%
• Weight variation: 3.85 %
• Disintegration Time: 8 min
Active Drug:
Pindolol(10mg)&Clopamide(5mg) -5.36%
Starch – 75.64%
Steric Acid - 4%
Cross-linked polyvinyl pyrrolidine – 12%
Cellulose- 3%
Method – Wet Granulation

13. Pharmacokinetics
• Absorption
• Bioavailability
• Plasma protein binding
• Volume Of distribution
• Half-life
• Metabolism
• Clearance
• Excretion
Pharmacodynamics
Pindolol
Pindolol blocks beta receptors that are found in the heart.
This reduces the action of adrenaline and noradrenaline
on the heart, causing it to beat more slowly and with less
force
Clopamide
Clopamide works by causing the kidneys to increase the
amount of salts such as potassium and sodium that are
filtered out of the blood and into the urine. When these
salts are filtered out of the blood by the kidneys, they
draw water alongside them

14. How can we evaluate the effect
The patients should not take any drug before 2 weeks of the trial during this time the patient will
take one placebo tablet daily
Treatment commence with pindolol 10 mg daily, given in the mornings for 3 weeks
Pindolol 10 mg and Clopamide 5 mg were given twice daily for 9 weeks
Then analyses the blood pressure change

15. NEBIVOLOL(5mg)
Nebivolol is a beta blocker used to treat high blood pressure and heart
failure. As with other β-blockers, it is generally a less preferred treatment
for high blood pressure. It may be used by itself or with other blood
pressure medication. It is taken by mouth. Common side effects include
dizziness, feeling tired, nausea, and headaches. Serious side effects may
include heart failure and bronchospasm. Its use in pregnancy and
breastfeeding is not recommended.

16. Why This Study?
• Nebivolol is used to treat high blood pressure and heart failure. ACE inhibitors, angiotensin II
receptor antagonists, calcium channel blockers and thiazide diuretics are generally preferred over
beta blockers for the treatment of high blood pressure.
Formulation
Active Drug: Nebivolol (3.03%) 5mg
Starch-78.47%
Steric Acid-3%
Cellulose-3.5%
Cross-linked polyvinyl pyrrolidine-12%

17. Performance:
• Hardness: 5kg
• Friability: 0.3%
• Dissolution time : 5 min
• Weight variation: 7.5%
How Can We Evaluate The effect
Nebivolol is a third-generation β-blocker, with highest β1 selectivity and nitric-
oxide-derived vasodilatation. It also exhibits antiproliferative and antioxidant
property that has beneficial metabolic profile compared to second-generation β
blockers like atenolol. This study was planned to study the comparative effects of
nebivolol and atenolol on metabolic parameters in patients with essential
hypertension.

18. Thank You