Table of Contents 1.About the Organization 7 1.1Units of Hetero Drugs 8 1.1.1 The Formulation Unit (Jeedimetla, Unit III) 9 2.What is a Formulation? 10 2.1 Preformulation 10 3.Dosage Forms 11 4.Tablet Manufacturing Process 13 4.1 Batch Manufacturing Record 13 4.2 Flow Diagram of Production Process 13 4.2.1. Granulation 14 4.2.1.1. What is an Active Ingredient? 14 4.2.1.2. What is an Excipient? 14 4.2.1.3. Stages in Granulation 15 4.2.2. Compression 19 4.2.3. Coating 21 4.2.4. Inspection 23 5. Capsule 24 5.1 Capsule Shell type 24 5.1.1. Hard Shelled Capsules 24 5.1.2. Soft Shelled Capsules 25 5.2 Capsule Production 25 5.2.1. Granulation 25 1
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Table of Contents1.About the Organization 7
1.1Units of Hetero Drugs 8
1.1.1 The Formulation Unit (Jeedimetla, Unit III) 9
2.What is a Formulation? 10
2.1 Preformulation 10
3.Dosage Forms 11
4.Tablet Manufacturing Process 13
4.1 Batch Manufacturing Record 13
4.2 Flow Diagram of Production Process 13
4.2.1. Granulation 14
4.2.1.1. What is an Active Ingredient? 14
4.2.1.2. What is an Excipient? 14
4.2.1.3. Stages in Granulation 15
4.2.2. Compression 19
4.2.3. Coating 21
4.2.4. Inspection23
5. Capsule 24
5.1 Capsule Shell type 24
5.1.1. Hard Shelled Capsules 24
5.1.2. Soft Shelled Capsules 25
5.2 Capsule Production 25
5.2.1. Granulation 25
5.2.2. Filling 26
5.2.2.1. Automatic Filling Machine 26
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5.2.2.2. Capsule Sorter and Elevator27
5.2.2.3. Capsule Detection and Polishing 28
5.2.3. Sorting 29
5.2.3.1. Mini Capsule Sorter 29
5.2.3.2. Air Displacement Unit 29
5.2.4. Inspection 30
5.2.5. Packing 31
5.2.5.1. Blister Packing 32
5.2.5.2. Strip Packing 33
5.2.5.3. Container Packing 34
References 35
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1.About the Organization:
Hetero Drugs Limited is an Indian pharmaceutical company established in the year
1993, by Dr. B.Partha Saradhi Reddy, a PhD scientist and expertise in chemistry. It was
started by him with a vision to be recognized as an aggressive company that combines its
strength of R&D and manufacturing with definite advantages in terms of cost and chemistry
with a strong emphasis on quality of the products. The tag line of the company is “Where the
future started yesterday”.
Hetero is one of its kinds, of the very few companies which have been able to carve a
niche in the pharmaceutical industry given the present scenario where it requires a right blend
of intellectual strength, core competencies and a precise foresight for the future.
Hetero has revenues over $500 million and employs over 5000 people. Hetero is a
strong player in API(Active Pharmaceutical Ingredients) and finished dosages and its
manufacturing plants have approvals of USFDA (United States Food and Drug
Administration), WHO (World Health Organization) and cGMP (Current Good
Manufacturing Practices). It has marketing presence in over 100 countries.
Hetero drugs is the parent company in the Hetero group of companies and other
companies which are part of the group are Hetero Labs, Hetero Research Foundation,
Symbed Labs limited, Cirex Laboratories, GenX Pharma and also foreign subsidiaries such as
Invagen Inc, in US and Richmond labs in Argentina etc .Hetero also has its own retail chain
of pharmacy outlets in India named as “Hetero Pharmacy”.
It holds a leadership position in the manufacture of anti-retrovirals in Hyderabad.
Some of their anti-HIV drugs which have huge markets are Nevilast-30, Nevilast-40,
Zidolam-N, etc.
They were awarded license to make generic Oseltamivir Tamiflu, by the Swiss firm
Roche in 2005 .This generic is an anti-flu treatment for India and other developing countries.
This drug is widely seen as the most promising treatment for combating any future pandemic
of bird flu in humans. The company says that Hetero Drugs is among the first to demonstrate
that it is technically capable of making a reliable generic version of tamiflu, this decision
could make it easier and cheaper for poorer nations to acquire stocks of the drug.
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Also now in 2009, as the swine flu outbreak is spreading across the globe and various
health organizations and government agencies are piling up stocks of Oseltamivir (tamiflu) as
precautionary measure, hetero is helping many countries including India by supplying the
generic Oseltamivir under its brand name “Fluvir”
Few of the milestones of the company are:
National Award for “Best Efforts in Research and Development” from the Department
of Scientific and Industrial Research, Ministry of Science and Technology, Government
of India, in the year 1996.
Highest Exporter award (for the year 1999) against stiff competition from internationally
recognized domestic competitors.
Approval of the API facilities by USFDA for compliance to CGMP norms.
Approval of the finished dosage facilities by WHO for the supply of anti-retroviral drugs.
1.1Units of Hetero Drugs
With full-fledged marketing capabilities, the company has been able to market its
products in over 100 countries in Asia, Middle-east, Eastern Europe and Latin America. With
its compliance to the most stringent regulatory requirements, Hetero has today gained
foothold to market several of its APIs in the United States, Canada and Europe.
With all six manufacturing facilities being supported by excellent infrastructure and
compliance to the GMP requirements, Hetero has crossed numerous milestones in a
comparatively short period since its inception.
Among the six manufacturing units four are in Hyderabad, one is in Visakhapatnam,
and the other is in Himachal Pradesh. In Hyderabad, the units are located as mentioned
below:
Unit Location
1 Bonthapally(API)
2 Kazipally
3 Jeedimetla(Formulation)
4 Bonthapally(API)
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1.1.1 The Formulation Unit (Jeedimetla , Unit III)
The unit in Jeedimetla is divided into two blocks namely block A and block B. It has
been certified by ISO-9001:2000 for it maintaining clean and international standards in
quality and manufacturing procedures.
Installed production capacities of the facility on single shift basis per annum are as
follows:
Tablets 2.8 billion units
Capsules 250 million units
Liquid Orals 3.5 million units
The details of the blocks are as follows:
i. BLOCK A:
• Built up area of about 6510 sq.mt.
• Modular concept with unidirectional flow
• Spread in two floors
• Four modules /six packing lines
• Designed for solid dosage forms
• Approved by WHO, Geneva
ii. BLOCK B:
Built up area 16310 sq. mt.(GF+FF+SF)
Multi product concept
Designed for solid and liquid oral dosage forms
Manufacturing facility confined to ground and second floor.
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2. What is a Formulation?
Formulation (also called as Pharmaceutical formulation), in pharmaceutics, is the
process in which different chemical substances (called excipients), including the active drug
(called API), are combined to produce a final medicinal product.
Formulation studies involve developing a preparation of the drug which is both stable
and acceptable to the patient. For orally taken drugs, this usually involves incorporating the
drug into a tablet or a capsule. It is important to appreciate that a tablet contains a variety of
other substances apart from the drug itself, and studies have to be carried out to ensure that
the drug is compatible with these other substances.
2.1Preformulation:
Preformulation involves the characterization of a drug's physical, chemical, and
mechanical properties in order to choose what other ingredients should be used in the
preparation. In dealing with protein pre-formulation, the important aspect is to understand the
solution behaviour of a given protein under a variety of stress conditions such as freeze/thaw,
temperature, shear stress among others to identify mechanisms of degradation and therefore
its mitigation.
It is also important to check whether there are any unwanted interactions between the
preparation and the container. If a plastic container is used, tests are carried out to see
whether any of the ingredients become adsorbed on to the plastic, and whether any
plasticizers, lubricants, pigments, or stabilizers leach out of the plastic into the preparation.
Even the adhesives for the container label need to be tested, to ensure they do not leach
through the plastic container into the preparation.
Stability studies are carried out to test whether temperature, humidity, oxidation, or
photolysis (ultraviolet light or visible light) have any effect, and the preparation is analysed to
see if any degradation products have been formed. Formulation studies then consider such
factors as particle size, polymorphism, pH, and solubility, as all of these can influence
bioavailability and hence the activity of a drug. The drug must be combined with inactive
additives by a method which ensures that the quantity of drug present is consistent in each
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dosage unit e.g. each tablet. The dosage should have a uniform appearance, with an
acceptable taste, tablet hardness, or capsule disintegration.
3. Dosage Forms:
A dosage form is the physical form of a dose of medication, such as a capsule or
injection. The route of administration is dependent on the dosage form of a given drug.
Various dosage forms may exist for the same compound, since different medical
conditions may warrant different routes of administration. For example, persistent vomiting
may make it difficult to use an oral dosage form; in this case, it may be advisable to use either
an injection or a suppository. Also, specific dosage forms may be warranted for certain
medications, since there may be problems with stability, e.g. insulin cannot be given orally