Medicinal
Technologies -
Pravastatin Production Technology
Introduction
Romanian company, through its Germany
and Italy based associates, offers the technology for
production of Pravastatin. The technology offered does
not conflict with any existing patent. The technical
details and product specifications are: Name: 1-Napthalene-heptanoic
acid, 1,2,6,7,8,8a-hexahydro-b,d,6-trihydroxy-2-methyl-8-(2-methyl-1-pxpbutoxy)-monosodium
salt Empirical formula: C23 H34 NaO7 Molecular weight:
446.5 Sodium Description: White to off-white granular
powder Identification by IR: Complies with test Solubility:
Soluble in water and glacial acetic acid, insoluble
in acetone, dichloroethane, hexane, and acetonitrile
Water by Karl Fisher (% w/w): NMT 6.0 Assay: (% w/w):
NLT98.0 HPLC on dried basis Strain classification: Pravastatin
is produced by microbial hydroxylation of Compactin
(ML-236B Na) using Streptomyces carbophilis, in this
case a mutant selected for high productivity. Pharmaceutical
use: Coronary artery disease is an exceptionally important
problem in industrial society and is often associated
with arteriosclerosis, a condition in which esterified
and free cholesterol is deposited in thinner walls of
coronary arteries. Extensive epidemiological studies
have established a link between abnormally high level
of low density lipoprotein cholesterol and the incidence
of coronary arteriosclerosis. Pravastatin is a potent
inhibitor of 3-hydroxy-3methylglutaryl coenzyme A (HMG
CoA) reductase. This enzyme catalyzes the conversion
of hydroxymethylglutarate to mevanolate, which is an
early and rate limiting step in biosynthesis of cholesterol.
The effectiveness of Pravastatin in
lowering cholesterol has been confirmed clinically and
it is approved for the treatment of primary hypercholesterolemia.
Process description: Streptomyces carbophilus is grown
on agar medium for 7-8 days. Flasks are inoculated with
a piece of well grown agar culture and cultivated on
a shaker. After 48 hours cultivation time the culture
is completely transferred to the production fermenter.
The productive fermenter is fed with sterile solution
of Glucose to maintain the optimal concentration of
Carbon source and pH. During the fermentation samples
are taken to check the conversion of compactin to pravastatin.
The fermentation broth is transferred to the recovery
section where the product is extracted by solvents,
lactonised and then converted to Sodium salt of Pravastatin.
It is re-crystallised to get the pharma grade material
Asian and Pacific Centre for Transfer
of Technology
APCTT Building
C-2 Qutab Institutional Area
P.O.Box - 4575
New Delhi - 110 016
Tel : 91-11-26966509
Fax : 91-11-26856274
