Detailed Project Report on active pharma ingredients (api) [azithromycin, alpha lipoic acid, pregablin, naproxen, ketoprofen]

ACTIVE PHARMA INGREDIENTS (API) [AZITHROMYCIN, ALPHA LIPOIC ACID, PREGABLIN, NAPROXEN, KETOPROFEN]

[CODE NO.4237]  

The Active Pharmaceutical Ingredient Industry is the organ by which active pharmaceutical ingredients are manufactured from raw materials through both chemical and physical means. Depending on the complexity of the molecule required, synthesis of APIs might need multi-step complex chemistry utilizing a range of processing technologies.

The leading manufacturer of APIs today is TAPI (Teva Active Pharmaceutical Ingredients). Specializing in range of API-related fields, TAPI works in areas such as chemical synthesis, fermentation, and chromatography and plant extraction and now has the industry’s largest portfolio of over 300 API products. In 2011 alone they achieved third-party sales of around $750 million.

Dr. Reddy’s is another leading manufacturer with 60 APIs for drug use, diagnostic kits and biotechnology products. Aurobindo and Cipla manufacture 200 APIs each, exporting their products to well over 200 countries worldwide. Other notable manufacturers are Sandoz-Lek-Biochemie, Ranbaxy, Matrix and Sun.

APIs are commonly referred to as ‘bulk pharmaceuticals’ and are in fact usually made in places at quite a distance to where tablets, suspensions and liquids are manufactured. Today, the greatest concentrations of API manufacturers are located around Asia, specifically in India and China. 

This has led to more and more companies to outsource API manufacturing to such places, which has the main benefit of eliminating the need to invest in highly expensive equipment and infrastructure – which on top of everything can also be complicated to install and maintain. A good example can be found with AstraZeneca, who manufacture 85% of its APIs but are currently in the process of withdrawing from all API production in favor of outsourcing.

Regardless of where the active pharmaceutical ingredient is made, companies must adhere to strict safety and quality standards set by the country where it will be used. So those APIs manufactured in China or India for use in the United States must still be inspected and licensed by the FDA. Similarly, if the API is intended for use in Europe, they would need to meet regulations set by the European Medicines Agency. Regular inspection outside the country of use however can prove difficult with counterfeiting and contamination being high on the list of various agencies’ concerns. For instance, since 2008, the FDA has considerably increased its overseas staff as a way of attempting to eliminate these problems. As a result, countries such as India have gained their foothold in the global market and now have around 75 FDA-approved manufacturing facilities for API synthesis.

Today there are more and more calls for API manufacturers to go green – that is to say, to reduce the waste they produce. Every year, large pharmaceutical manufacturers can produce anywhere from 3000 to 5000 tons of hazardous waste each.  If one were to ask any reputable API manufacturer how they would like to improve the process, they’d likely say to make the reactions faster, or to make them cheaper. Ironically the first steps in reducing waste from API synthesis would be to reduce the number of reactions required to produce a given molecule.  Therefore though the goal may be different, the means turn out to be the same as fewer reactions mean less solvent to dispose of. Another step in going green is to find different solvents and catalysts that are not only more efficient, but are also better for the environment.

Naproxen is a nonsteroidal anti-inflammatory drug (NSAID).

Naproxen is a pain medication that relieves inflammation and joint stiffness. Other NSAIDs in the same medication class include acetylsalicylic acid, diclofenac, ibuprofen, and meloxicam.

Naproxen works by blocking the enzyme that produces prostaglandins. Prostaglandins play an essential role in inflammation. The body produces them at the site of injured tissue, and they cause redness, heat, swelling, and pain.

Naproxen is available as naproxen or naproxen sodium. The major difference between naproxen and naproxen sodium is that naproxen sodium is more rapidly absorbed.

The body reaches peak levels of naproxen in 2–4 hours and naproxen sodium in 1–2 hours, meaning that it absorbs naproxen sodium faster than regular naproxen.

Alpha-lipoic acid 

Generic name: alpha-lipoic acid (AL fa lye POE ik AS id)

Brand name: Alpha Lipoic Acid, Alpha-Lipoic-Acid-300, Alpha Lipoic

Dosage forms: oral capsule (100 mg; 200 mg; 300 mg; 600 mg); oral tablet (100 mg; 300 mg; 50 mg)

Drug class: Nutraceutical products

Alpha-lipoic acid is an antioxidant also known as Acetate Replacing Factor, ALA, Biletan, Lipoicin, Thioctan, and many other names.

Alpha-lipoic acid is a naturally occurring fatty acid that can be found in many foods such as yeast, spinach, broccoli, potatoes, and organ meats such as liver or kidney.

Alpha-lipoic acid has been used in alternative medicine as a possibly effective aid in weight loss, treating diabetic nerve pain, healing wounds, lowering blood sugar, improving skin discoloration caused by vitiligo, and decreasing complications of coronary artery bypass graft (CABG) surgery. Alpha-lipoic acid may have been combined with other plants or extracts in a specific preparation to treat these conditions.

Alpha-lipoic acid has also been used to treat rheumatoid arthritis, Alzheimer's disease, alcoholic liver problems, altitude sickness, heart-related nerve problems, HIV-related brain problems, or eye problems caused by diabetes. However, research has shown that alpha-lipoic acid may not be effective in treating these conditions.

Azithromycin

Generic name: azithromycin (a ZITH roe MYE sin)

Brand name: Azasite, Azithromycin 3 Day Dose Pack, Azithromycin 5 Day Dose Pack, Zithromax, Zithromax TRI-PAK, Zithromax Z-Pak, Zmax

Drug class: Macrolides

Azithromycin is an antibiotic that fights bacteria.

Azithromycin is used to treat many different types of infections caused by bacteria, such as respiratory infections, skin infections, ear infections, eye infections, and sexually transmitted diseases.

Azithromycin may also be used for purposes not listed in this medication guide.

Ketoprofen 

Generic name: ketoprofen (kee toe PROE fen)

Brand name: Orudis, Oruvail, Actron, Orudis KT

Dosage forms: oral capsule (25 mg; 50 mg; 75 mg); oral capsule, extended release (200 mg)

Drug class: Nonsteroidal anti-inflammatory drugs

Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to treat pain or inflammation caused by arthritis.

The ketoprofen regular capsule is also used to treat mild to moderate pain, or menstrual pain.

Only ketoprofen extended-release capsules are used for treating arthritis. This form of ketoprofen will not work fast enough to treat acute (immediate) pain.

Pregabalin 

Generic name: pregabalin (pre GAB a lin)

Brand name: Lyrica, Lyrica CR

Dosage forms: oral capsule (100 mg; 150 mg; 200 mg; 225 mg; 25 mg; 300 mg; 50 mg; 75 mg); oral solution (20 mg/mL); oral tablet, extended release (165 mg; 330 mg; 82.5 mg)

Drug class: Gamma-aminobutyric acid analogs

Pregabalin is an anti-epileptic drug, also called an anticonvulsant. It works by slowing down impulses in the brain that cause seizures. Pregabalin also affects chemicals in the brain that send pain signals across the nervous system.

Pregabalin is used to treat pain caused by fibromyalgia, or nerve pain in people with diabetes (diabetic neuropathy), herpes zoster (post-herpetic neuralgia), or spinal cord injury.

Pregabalin is also used with other medications to treat partial onset seizures in adults and children who are at least 1 month old.

COST ESTIMATION

Plant Capacity                                    250 Kg./Day

Land & Building (3000 sq.mt.)  Rs. 4.06 Cr

Plant & Machinery                              Rs. 1.15 Cr

Working Capital for 2 Months    Rs. 5.30 Cr

Total Capital Investment                  Rs. 10.80 Cr

Rate of Return                                     38%

Break Even Point                                42%

• INTRODUCTION
• ALPHA-LIPOIC ACID
• AZITHROMYCIN
• KETOPROFEN
• PREGABALIN
• CHEMISTRY AND MANUFACTURERS OF API
• CHEMISTRY
• MANUFACTURERS
• CARBIDOPA API
• DILTIAZEM
• PRECAUTIONS
• GEMFIBROZIL API
• THERAPEUTIC EFFECTS
• PRECAUTIONS AND TOXICITIES
• DRUG INTERACTIONS
• AZITHROMYCIN API
• TREATMENT
• MECHANISM OF ACTION
• SIDE EFFECTS
• ACTIVE PHARMA INGREDIENTS
• APIS ARE GENERALLY MANUFACTURED THROUGH A VARIETY OF PROCESSES THAT INCLUDE:
• MARKET OVERVIEW OF API
• KEY MARKET ANALYSIS
• GLOBAL OVERVIEW OF API
• MARKET OF INDIAN PHARMACEUTICAL INDUSTRY
• COMPOSITION OF INDIAN PHARMA MARKET
• PHARMA EXPORT TO CONTINUE WITNESSING POSITIVE GROWTH
• CHALLENGES FACED BY INDIAN API INDUSTRY
• STRICTER IMPLEMENTATION OF POLLUTION CONTROL NORMS
• INTERPRETATION OF DPCO,
• NO TAX INCENTIVES, HIGHER UTILITIES AND BORROWING COST
• LACK OF MEGA BULK DRUG PARKS
• ISSUES FACED BY FERMENTATION INDUSTRY
• RECOMMENDATIONS
• FASTER ENVIRONMENT CLEARANCE
• ENCOURAGE MANUFACTURING BY PROVIDING A FISCAL STIMULUS FOR APIS AND INTERMEDIATES
• FOR FERMENTATION PRODUCTS
• RECOMMENDATIONS – IMMEDIATE
• ACCOMMODATIVE PRICING POLICY UNDER DPCO,
• FINANCIAL INCENTIVES
• RECOMMENDATIONS – LONG TERM
• INDUSTRY–ACADEMIA INITIATIVES
• FACILITATE ALTERNATIVE SOURCES OF IMPORT
• USES AND APPLICATION OF NAPROXEN
• DOSAGE AND FORM OF NAPROXEN
• MILD TO MODERATE PAIN
• OSTEOARTHRITIS, RHEUMATOID ARTHRITIS, ANKYLOSING SPONDYLITIS
• ACUTE GOUT ATTACKS
• JUVENILE RHEUMATOID ARTHRITIS
• HEADACHES
• MANUFACTURING PROCESS OF AZITHROMYCIN
• CHEMICAL REACTION
• MATERIAL OR MASS BALANCE
• MANUFACTURING PROCESS OF PREGABALIN
• STAGE- I
• STAGE-II
• STAGE-III
• PROCESS FLOW DIAGRAM
• MATERIAL BALANCE OF PREGABALIN
• STAGE-I
• STAGE-II
• STAGE-III
• MANUFACTURING PROCESS OF NAPROXEN
• STAGE-I
• STAGE-II
• STAGE-III
• STAGE-IV
• STAGE-V
• STAGE-VI
• STAGE-VII
• PROCESS FLOW DIAGRAM
• RAW MATERIALS
• MANUFACTURING PROCESS OF ALPHA LIPOIC ACID
• STAGE-1
• STAGE-II
• STAGE-III
• MANUFACTURING PROCESS OF KETOPROFEN
• STEP-I
• STEP-II
• OTHER PROCESS OF API MANUFACTURE
• MANUFACTURING PROCESS OF M-BROMO ANISOLE
• REACTION
• PROCESS FLOW DIAGRAM OF M-BROMO ANISOLE
• (BATCH 400 KGS)
• MANUFACTURING PROCESS OF ETHYL TRIPHENYL PHOSPHONIUM BROMIDE (BATCH 135 KG)
• PROCESS FLOW DIAGRAM (BATCH 135 KG)
• MANUFACTURING PROCESS OF CINNAMYLALDEHYDE (BATCH 560 KG)
• PROCESS FLOW DIAGRAM
• MANUFACTURING PROCESS OF M-PHENOXY BENZYL 
• ALCOHOL (BATCH 175 KG)
• PROCESS FLOW DIAGRAM BATCH-175 KG
• MANUFACTURING OF BENZYL ALCOHOL BATCH- 187 KGS
• PROCESS FLOW DIAGRAM
• MATERIAL BALANCE
• DISTILLATORY
• MANUFACTURING PROCESS OF ALPRAZOLAM
• PROCESS FLOW DIAGRAM
• MANUFACTURING PROCESS OF METHYLPHENIDATE
• PROCESS FLOW DIAGRAM
• PRINCIPLES OF PLANT LAYOUT
• STORAGE LAYOUT:
• EQUIPMENT LAYOUT:
• SAFETY:
• PLANT EXPANSION:
• FLOOR SPACE:
• UTILITIES SERVICING:
• BUILDING:
• MATERIAL-HANDLING EQUIPMENT:
• RAILROADS AND ROADS:
• MAJOR PROVISIONS IN ROAD PLANNING FOR MULTIPURPOSE SERVICE ARE:
• PLANT LOCATION FACTORS
• PRIMARY FACTORS
• 1. RAW-MATERIAL SUPPLY:
• 2. MARKETS:
• 3. POWER AND FUEL SUPPLY:
• 4. WATER SUPPLY:
• 5. CLIMATE:
• SPECIFIC FACTORS
• 6. TRANSPORTATION:
• A. AVAILABILITY OF VARIOUS SERVICES AND PROJECTED RATES
• 7. WASTE DISPOSAL:
• 8. LABOR:
• 9. REGULATORY LAWS:
• 10. TAXES:
• 11. SITE CHARACTERISTICS:
• 12. COMMUNITY FACTORS:
• 13. VULNERABILITY TO WARTIME ATTACK:
• 14. FLOOD AND FIRE CONTROL:
• EXPLANATION OF TERMS USED IN THE PROJECT REPORT
• 1. DEPRECIATION:
• 2. FIXED ASSETS:
• 3. WORKING CAPITAL:
• 4. BREAK-EVEN POINT:
• 5. OTHER FIXED EXPENSES:
• 6. MARGIN MONEY:
• 7. TOTAL LOAD:
• 8. LAND AREA/MAN POWER RATIO:
• PROJECT IMPLEMENTATION SCHEDULES
• INTRODUCTION
• PROJECT HANDLING
• PROJECT SCHEDULING
• PROJECT CONSTRUCTION SCHEDULE
• TIME SCHEDULE
• ADDRESSES OF RAW MATERIAL SUPPLIERS
• PLANT AND EQUIPMENT SUPPLIERS
• 
  

APPENDIX – A:

01. PLANT ECONOMICS

02. LAND & BUILDING

03. PLANT AND MACHINERY

04. OTHER FIXED ASSESTS

05. FIXED CAPITAL

06. RAW MATERIAL

07. SALARY AND WAGES

08. UTILITIES AND OVERHEADS

09. TOTAL WORKING CAPITAL

10. TOTAL CAPITAL INVESTMENT

11. COST OF PRODUCTION

12. TURN OVER/ANNUM

13. BREAK EVEN POINT

14. RESOURCES FOR FINANCE

15. INSTALMENT PAYABLE IN 5 YEARS

16. DEPRECIATION CHART FOR 5 YEARS

17. PROFIT ANALYSIS FOR 5 YEARS

18. PROJECTED BALANCE SHEET FOR (5 YEARS)