This document discusses statins, which are drugs used to lower cholesterol levels and prevent cardiovascular disease. It begins by explaining that hyperlipidemias involve elevated levels of cholesterol or triglycerides in the blood. Statins work by inhibiting HMG-CoA reductase, a rate-limiting enzyme in cholesterol biosynthesis in the liver. This decreases cholesterol synthesis and lowers LDL cholesterol levels. Lovastatin was the first statin approved by the FDA and is produced through the fermentation of fungi such as Aspergillus terreus. The document then describes the fermentation and purification process used to produce lovastatin through solid state fermentation of A. terreus and extraction using organic solvents.

1. STATINS
PHARMACEUTICAL PROCESS CHEMISTRY
PRESENTED BY
Mr. Darshan N U B Pharm ( M Pharm)
M Pharmacy II Semester
Dept. of Pharmaceutical Chemistry
SACCP
PRESENTING TO
Mr. Purushotham K N M Pharm ( Ph.D)
ASST. Professor
Dept. of Pharmaceutical Chemistry
SACCP
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2.  Hyper-lipoproteinemias (HPL) are conditions in which the concentration of cholesterol
or triglyceride carrying lipoproteins in the plasma is elevated above normal.
 Increase in lipoprotein can hasten the development of atherosclerosis and is a risk factors
for myocardial infarction (MI)
 Lipids and proteins form complexes called lipoproteins & circulate in blood vessels.
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3. Lipoproteins
Low density lipoprotein (LDL)
< 2.0 milli mol/liter
High density lipoprotein
(HDL) > 1.0 mmol/liter in
men and >1.2 in women
Chylomicrons
0.4 mmol/L
Very low density lipoproteins
(VLDL) 0.77 mmol/liter
Types of Lipoprotein
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4. Hypolipidaemias
• These are the drugs which lower the levels of lipids and lipoproteins in blood used to
prevent cardiovascular disease by retarding the atherosclerosis in hyper-lipidaemia
individuals
• Drugs used to treat hyperlipidaemia are
 Lovastatin, Simvastatin, Atorvastatin
 Cholestyramine, Colestipol
 Clofibrate, Gemfibrozil
 Nicotinic Acid
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Biosynthesis of Cholesterol

6. Mechanism of Action of Statins (HMG CoA reductase Inhibitors)
• Hydroxymethyl glutaryl CoA is the rate controlling enzyme in the biosynthesis of
cholesterol
• Lovastatin and its congeners are structurally similar to HMG CoA and therefore
competitive inhibitors of the enzyme HMG-CoA reductase. The synthesis of
cholesterol in the liver is reduced. There is an increase in the expression of hepatic
LDL receptor. So that more of LDL is taken up from the circulation. As a result
plasma levels of LDL cholesterol and triglycerides fall.
• Concentration of HDL- cholesterol increases by 10%
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7. Statins
Inhibit the HMG CoA reductase
Decrease synthesis of Cholesterol
Decrease LDL
Statins to be useful lowering morbidity and mortality in patients with coronary
heart disease. Hence they are used in patients with MI, angina etc
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9.  Lovastatin was the first statin drug which was approved by USFDA In the
year 1987
 It is a potent drug that is used to control increased serum cholesterol level,
there by preventing hypercholesterolemia and associated health issue.
 It is a competitive inhibitor of the enzyme HMG CoA reductase which
catalyses rate limiting step in cholesterol biosynthesis
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Structure of lovastatin

10. Fungal organism reported for lovastatin production
• Aspergillus
• Penicillium citrinum
• Monascus ruber
• Trichoderma
• Pleurotus widely reported soil fungi capable of lovastatin production
• Commercial production of lovastatin employs a Aspergillus terreus soil fungus
• Several production media have been evaluated for lovastatin production by SmF ( submerged
fermentation)
• Increased yield by supplementation with carbon, nitrogen, aminoacids, vitamins, etc.
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11. Fermentation Techniques
• Different fermentation techniques including solid state fermentation (SSF)
and submerged fermentation (SMF) can be used for statin production.
• Large scale commercial production utilises submerged batch fermentation
• There is a controlled aeration & agitation in a bioreactor during SMF, which
increases the oxygen mass transfer and constant distribution of nutrients to
fungal mycelia, resulting in increased production of statins.
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15. Materials and Methods
Culturing of Aspergillus terreus by Solid State Fermentation (SSF)
• Wheat bran (40g) as substrate
• Inoculated with spore suspension (107/8ml spores) of A. terreus
(KM017963)
• Incubated at 280C for 7 days
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16. Extraction
• Inoculated substrate was dried at 40◦C for 24h
• Crushed to powder
• Ethyl acetate (150 ml) was added
• Filtrate was dried using rotary vacuum evaporator
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17. Purification of lovastatin
• One gram of dried crude lovastatin extract was loaded on to pre-
packed silica gel column
• Elution with benzene (100%), and combination of
Benzene: Acetonitrile in the following ratio 95:5, 90:10, 85:15, 80:20
Acetonitrile (100%)
• Thin Layer Chromatography (TLC)
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18. Detection of Lovastatin by Thin Layer Chromatography
(TLC)
• Organic phase (20 µl) was spotted on TLC plate
• Dichloromethane: Ethyl acetate (70:30)
• Rf comparison with standard Lovastatin
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19. REFERENCE
• Essential of Medical Pharmacology K D Tripathi 8th edition.
• Istvan, E 2003 statin inhibition of HMG-CoA reductase : Atheroscle.
Suppl. 4,3-8. doi:10.1016/s1567-5688(03)00003-5.
• Google , Wikipedia date 28/08/2022
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20. THANK YOU
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