THE HISTORY OF CODEINE
According to the World Health Organization, codeine is the most commonly
used opiate in the world. Codeine was usually administered orally and has been
applied in clinical medicine for quite a long time. Codeine also is currently approved
for use as an oral analgesic for mild-to-moderate degrees of pain and as an antitussive
for suppression of cough which is used in low dose. Codeine is the least addictive and
kind of the safest opiate among all opiate drugs that have been prescribed nowadays
and the most widely used analgesic drugs or mostly known as “pain-killers”. Even
though codeine is the least addictive and safest, it doesn’t mean that codeine cannot
give harm to people because many become physically and mentally addicted after
extended or repeated use.
Codeine is a natural alkaloid which is extracted directly from the seeds of the
opium poppy, Papaver Somniferum. In early 1704, opium was quite known in England
and at that time, most of opium was sold in elixirs form, for example paregoric which
function as pain soothers. In 1804, a German pharmacist, Friedrich Wilhelm Adam
Serturner has discovered how to isolate and extract morphine crystals that obtained
from opium poppy seed. Codeine has been discovered and was first isolated in 1830
by a French chemist, Pierre Robiquet. The name, of “codeine” comes from the Greek
word that refers to the head of the poppy plant.
Drug manufacturers only can depend on using the tar from opiate poppies to
produce opiate drugs such as codeine, morphine and other opiate drugs. This problem
happened since President’s Nixon’s War on Drugs burden the people by make them
difficult to obtain the poppies that mostly grow in the country that are unfriendly to
America’s pharmaceutical interest, for example Afghanistan. Most drug manufacturers
need to face with heroin dealers to purchase raw codeine product. This problem has
led the chemists to discover a method to synthesize codeine from coal tar, which has
freed the drug companies from competing with the illicit drug cartels.
SYNTHESIS OF CODEINE
METHYLATION
The methylation of morphine is one of the key operations of the opium
alkaloid industry. About 90% of the manufactured morphine is converted into
codeine, which is the methyl ether of the phenolic hydroxyl of the morphine.
Codeine can be directly obtained by extracting the opium. However,
most codeine are prepared by methylation of morphine in a phase transfer
reaction. This is because, even though some codeine can be obtained from
opium directly, the quantity is still not enough to meet the extensive use of this
alkaloid as a valuable medicinal agent. Codeine is the most used by people
than morphine, so the process of methylation of morphine has been used to
synthesis more codeine needed. In this process, the phenolic hydroxyl of the
morphine is methylated with trimethylphenylammonium hydroxide. The first
step is, dissolving the dry morphine in the solution of potassium hydroxide Dry
morphine is dissolved in a solution of potassium hydroxide in the ethanol with
which
has
low
water
content.
After
that,
the
methylating
agent,
trimethylphenylammonium hydroxide was inserted in the solution. Then, the
solution will be heated to evaporate the ethanol. Next, the solution was slowly
cooled. After cooling, the water is added and then the solution is acidified with
sulfuric acid. Acidifying the solution causing the product to separate, and the
alcohol was removed using distillation. Sodium hydroxide was used to
precipitate the codeine. Precipitation of codeine showed that codeine was
insoluble in alkaline solution. The unreacted morphine is held in solution by the
sodium hydroxide. The crystalline form of codeine is purified by crystallization
as the sulfate.
PROPERTIES OF CODEINE
1. Colour and form
Codeine is colourless and can came out as white crystals or powder.
2. Boiling point
The boiling point of codeine is 480°F at 22mm/Hg
3. Melting point
The melting point of codeine is 309 to 313 °F (after drying at 176° F)
4. Solubility
The solubility of codeine can be less than 1 mg/mL at 70° F or not really soluble
in water or soluble in alcohol
5. Density
The density of codeine is 1.32 at 68 °F
STRUCTURE OF CODEINE

The molecular formula of codeine is C18H21NO3 .

The chemical name of codeine is (5alpha,6alpha)-7,8-didehydro-4,5-epoxy-3methoxy-17-methylmorphinan-6-ol

The other names of codeine are methylmorphine, morphine monomethyl ether.

The molecular weight of codeine is 299.37 g/mol
2D Chemical structure
3D Chemical structure
of codeine
of codeine
Crystal structure
of codeine
APPLICATION OF CODEINE
1) Analgesic
Codeine is a weak opioid analgesic which achieves its analgesic action through
metabolisation to morphine in the liver by the liver enzyme, CYP2D6. Usually 5 to 15%
of a dose of codeine is metabolized to morphine. Approximately 6 to 10% of
Caucasians and 1 to 2% of Asians are lack the CYP2D6 enzyme because of genetic
differents. The lack of the enzyme causing the difficulty in conversion of codeine to
morphine and are hard to achieve any pain relief with codeine
2) Antitussive
Antitussive is cough suppressants. Codeine is used with combinations of other
medications such as antihistamines, decongestants. This combination product is used
to treat symptoms that resulted from the flu, allergies, fever, or breathing diseases.
Codeine as antitussive help affect the specific part in the brain to reduce the cough
urgency. Decongestants can help to soothe stuffy nose symptoms. Antihistamines can
relieve watery and itchy eyes, runny nose or sneezing. Codeine should not be used
by children who are younger than 18 years old because it can give serious side effects
to them.
3) Anti-diarrheal
Therapeutic doses of codeine can increase the net absorption in large intestine, thus
reduce the stool volume by increasing the contact time between luminal fluid and
mucosa cells. Codeine do not regulate intestinal absorption, so there is no increase of
rate of absorption by cells.