Detailed Project Report (DPR) on ephedrine

EPHEDRINE

[CODE NO.3827]  

Ephedrine is a medication and stimulant. It is often used to prevent low blood pressure during spinal anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in nasal congestion. It can be taken by mouth or by injection into a muscle, vein, or just under the skin. Onset with intravenous use is fast, while injection into a muscle can take 20 minutes, and by mouth can take an hour for effect. When given by injection it lasts about an hour and when taken by mouth it can last up to four hours.

Common side effects include trouble sleeping, anxiety, headache, hallucinations, high blood pressure, fast heart rate, loss of appetite, and inability to urinate. Serious side effects include stroke, heart attack, and abuse. While likely safe in pregnancy, its use in this population is poorly studied. Use during breastfeeding is not recommended. Ephedrine works by increasing the activity of the α and β adrenergic receptors.

Ephedrine was first isolated in 1885 and came into commercial use in 1926. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. The wholesale cost in the developing world is about US$0.69–1.35 per dose. In the United States it is not very expensive. It can normally be found in plants of the Ephedra type. Dietary supplements containing ephedrine are illegal in the United States, with the exception of those used in traditional Chinese medicine, where its presence is noted by má huáng.

Ephedrine promotes modest short-term weight loss, specifically fat loss, but its long-term effects are unknown. In mice, ephedrine is known to stimulate thermogenesis in the brown adipose tissue, but because adult humans have only small amounts of brown fat, thermogenesis is assumed to take place mostly in the skeletal muscle. Ephedrine also decreases gastric emptying. Methylxanthines such as caffeine and theophylline have a synergistic effect with ephedrine with respect to weight loss. This led to creation and marketing of compound products. One of them, known as the ECA stack, contains ephedrine with caffeine and aspirin. It is a popular supplement taken by bodybuilders seeking to cut body fat before a competition.

Ephedrine  is a sympathomimetic amine used for  allergic conditions,   CNS  (Central  Nervous  System)  stimulation,   and prophylaxis  and  treatment of hypotension. It is  useful  as  an adjunct  to  neostigmine in the treatment of  myasthenia  gravis. Either  the  sulphate or hydrochloride is used for  the  systemic effects  of  the  alkaloid. Sterile  solutions  can  be  injected subcutaneously,  intramuscularly,   or   intravenously.    Tropical

application to the respiratory or conjuctival mucosa is common.

1. AO.5 - 1.0% solution is used as a nasal decongestant.

2. A 4% solution is used as a mydriatic.

3. The 1-3% solution of the free base in oil is available for tropical use.

The preferred natural source of ephedrine is "Ma  Haung" which is a mixture of E. equisetina, E. Sinica, and E. distachya. The  yield  of  crude  alkaloid is in the range  of  0.5.  -  2%, depending  on  the species, of this, upto 90% may  be  ephedrine. Ephedrine is soluble in water, alcohol, chloroform, and ether. It melts over a range of 33-42~c, depending on the water content.

COST ESTIMATION

Plant Capacity                                 5.00 TON/day

Land & Building (3000 sq.mt.)    Rs. 4.00 Cr    

Plant & Machinery                         Rs. 3.09 Cr 

Working Capital for 2 Months    Rs. 17.52 Cr 

Total Capital Investment            Rs. 24.93 Cr 

Rate of Return                             42%

Break Even Point                       34%

• INTRODUCTION
  
• PROPERTIES OF EPHEDRINE
• PROPERTIES OF EPHEDRINE HYDROCHLORIDE
• CLASSIFICATION (FORMS)
• NOMENCLATURE
• GRADES
• MECHANISM OF ACTION
• COMPOUNDS WITH DECREASING Α-RECEPTOR AFFINITY
• MEDICAL USE
• OTHER USES
• USES AND APPLICATIONS
• CHEMISTRY AND NOMENCLATURE OF EPHEDRINE
• CONTRAINDICATION AND ADVERSE EFFECTS OF EPHEDRINE
• ADVERSE EFFECTS
• STRUCTURE OF EPHEDRINES
• FIGURE: FREUDENBERG AND LEITHE REPRESENTATION OF EPHEDRINE 
•    1A AND PSEUDOEPHEDRINE 2A.
• FIGURE. STABLE CONFORMATIONS OF EPHEDRINE 1B AND PSEUDOEPHEDRINE
• FIGURE. EPHEDRINE STEREOISOMERS.
• FIGURE: NOREPHEDRINE STEREOISOMERS.
• PHYSICAL PROPERTIES OF EPHEDRINES
• MARKET SURVEY AND GROWTH ASPIRATION OF INDIAN 
•    PHARMACEUTICAL INDUSTRY
• OPPORTUNITIES AND CHALLENGES FOR ACHIEVING VISION 2030
• OPPORTUNITIES
• EXHIBIT 3
• PATENT ANALYSIS
• A FOOTPRINT IN UNDERPENETRATED INTERNATIONAL MARKETS 
•    COULD INCREASE EXPORTS
• LEVERAGE INDIA'S STRENGTHS IN IT AND ITES – OPTIMIZE NEW 
•    AVENUES SUCH AS OTC
• CHALLENGES
• INDIA IS YET TO ACHIEVE UNIVERSAL HEALTHCARE ACCESS
• LACK OF A STABLE PRICING AND POLICY ENVIRONMENT FAVOURABLE 
•     FOR LONG-TERM INVESTMENT DECISIONS
• LACK OF CAPABILITIES IN THE INNOVATION SPACE
• DEPENDENCE ON EXTERNAL MARKETS FOR INTERMEDIATES AND APIS
• INDIAN PHARMA’S ERODING COMPETITIVE ADVANTAGE IN THE US 
•   GENERICS MARKET & LIMITED PRESENCE IN OTHER MARKETS 
•    AND PRODUCTS
• INCREASED SCRUTINY IN QUALITY COMPLIANCE WHEN SUPPLYING 
•    TO INTERNATIONAL MARKETS
• OVERVIEW OF INDIAN PHARMACEUTICAL INDUSTRY
• IMPORT DATA OF EPHEDRINE
• EXPORT DATA OF EPHEDRINE
• MARKET POSITION OF API (ACTIVE PHARMA INGREDIENT)
• INDIA API MARKET TRADE (%), FY 2016
• SHARE OF INDIA IN GLOBAL API MARKET (%), FY 2016
• SHARE OF INDIA IN GLOBAL API MARKET
• INDIAN API DOMESTIC CONSUMPTION MARKET FUTURE OUTLOOK
• INDIAN API DOMESTIC CONSUMPTION MARKET (BILLION US$), 
•     FY 2015-FY 2022
• MAJOR APIS IN THE INDIAN API MARKET
• MAJOR APIS IN THE INDIAN API MARKET
• DRIVERS
• RISING HEALTHCARE EXPENDITURE
• HEALTHCARE EXPENDITURE (US$ PER HEAD), 2012-2016
• INCREASING DISPOSABLE INCOMES
• PERSONAL DISPOSABLE INCOME (TRILLION US$), 2012-2016
• GROWING GERIATRIC POPULATION
• INDIAN POPULATION - 60 YEARS OR ABOVE (MILLION), 2015 & 2030
• INCREASING INCIDENCES OF CHRONIC DISEASES
• CARDIOVASCULAR DISEASES
• DIABETES
• INDIA - NUMBER OF PEOPLE WITH DIABETES (MILLION), 2015 & 2040
• PATENT EXPIRY OF BLOCKBUSTER DRUGS
• LIST OF BLOCKBUSTER DRUGS LOSING PATENT (2016-2022)
• INCREASED CONSUMPTION OF GENERIC DRUGS
• INVENTION OF NEW GENERATION OF APIS
• CHALLENGES
• OVER DEPENDENCE ON CHINA FOR IMPORTS
• API IMPORT FROM CHINA (BILLION US$), FY 2012 TO FY 2015
• THE REASONS FOR LOW MANUFACTURING COST OF API IN CHINA ARE:
• GLOBAL MARKET POSITION OF EPHEDRINE
• PRODUCTION SCHEMES OF EPHEDRINE
• PRODUCTION SCHEMES OF EPHEDRINE
• (1) EXTRACTION FROM EPHEDRA PLANTS
• (2) FERMENTATION OF SUGAR FOLLOWED BY AMINATION
• (3) CHEMICAL SYNTHESIS: BROMINATION OF PROPIOPHENONE 
•    FOLLOWED BY AMINATION
• PROCESS OF MANUFACTURE
• MANUFACTURING PROCESS:-
• REACTION WITH ACTIVELY FERMENTING GLUCOSE SOLUTION:-
• CONDENSATION WITH METHYLAMINE:-
• REDUCTION TO PRODUCE 1-EPHEDRINE:-
• CONVERSION TO EPHEDRINE HYDROCHLORIDE:-
• PACKING AND FORWARDING:-
• PROCESS FLOW SHEET FOR THE MANUFACTURE OF 
•     EPHEDRINE HYDROCHLORIDE (KETOL)
• BIOSYNTHETICS OF EPHEDRINE (ORGANIC)
• OTHER METHODS:
• PREPARATION OF PROPIONYL CHLORIDE  AND PROPIOPHENONE
• EPHEDRONE [Α-METHYLAMINOETHYL PHENYL KETONE]
• DL -EPHEDRINE HYDROCHLORIDE
• SYNTHESIS
• ANOTHER METHOD:
• DL -EPHEDRINE HYDROCHLORIDE
• METHOD FOR MANUFACTURING EPHEDRINE OR PSEUDOEPHEDRINE
• METHYLAMINE SOLUTION PREPARING THESE SOLVENTS, THERE 
•     ARE TWO WAYS:
• MANUFACTURING PROCESS  OF PSEUDO EPHEDRINE HCL
• THE PROCESSING STAGES ARE AS FOLLOWS:-
• STAGE-1
• STAGE-2
• STAGE-3
• STAGE-4
• PROCESS FLOW DIAGRAM
• INNOVATION TWO STAGE PROCESS FOR THE MANUFACTURE 
•     OF EPHEDRINE
• STAGE 1
• STAGE 2
• EPHEDRINE AND ITS SALTS ISOLATION AND PROPERTIES
• EXPERIMENTAL
• EXTRACTION
• PREPARATION OF EPHEDRINE HCL BY FRACTIONAL CRYSTALLIZATION
• SEPARATION OF THE OXALATES BY DIFFERENCE OF SOLUBILITY
• PREPARATION OF PURE EPHEDRINE BASE
• PROPERTIES OF PURE EPHEDRINE
• PSEUDOEPHEDRINE
• ACTION OF HCL UPON EPHEDRINE. PREPARATION OF PSEUDOEPHEDRINE.
• THE MODELING AND 3D STRUCTURES OF EPHEDRINE HYDROCHLORIDE
• RAMAN SPECTRUM OF EPHEDRINE HYDROCHLORIDE
• PLANT LAYOUT
• SUPPLIERS OF RAW MATERIALS
• SUPPLIERS OF PLANT & MACHINERY

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)