HIJ Drug Manufacturing Factory

1
HIJ Drug Manufacturing Factory

• Ketamine

6S Chu Man
Hin, Hinson (9)
Chung Siu Wa, Jennifer (10)
Lau Yuk Ping, Isa (14)
2
(No Transcript)
3
Lead Compound Discovery
cause hallucinations(??), neurotoxicity(????) and
seizures(??)
phencyclidine (PCP)
A kind of an anesthetic (???)
Ketamine for replacement
4

• Laboratory Session

5
Molecular Modification
Ketamine
PCP
Cyclohexamine
Year
1959
1958
1962
6
Drug synthesis
Step 1
Cyclopentylmagnesium bromide
2-chlorobenzonitrile
7
Drug synthesis
Step 2
Br2
1-(2-chlorobenzoyl) cyclopentane
8
Drug synthesis
Step 3
CH3NH2 H2O
9
Drug synthesis
Step 4
Decalin (C10H18)
Methylimino derivative
10
Drug synthesis
Ketamine made!!
11
Formulation Development
12
Injection
10 ketoprofen
5 Lidocaine
10 ketamine
13
Injection
cyclobenzaprine
tramadol
clonidine
These are all longer-acting local
anaesthetics(???)
14
Liquid Aerosol Formulation
carriers
diluents
solubilizing or emulsifying agents
excipients
surfactants
15
Liquid Aerosol Formulation
carriers

• Examples
• Soya lecithin (?????)
• oleic acid (??)
• sorbitan trioleate (????????
• ?)

Preferred
16
Liquid Aerosol Formulation
diluents

• Examples
• Sterile water
• Saline(??)
• Buffered saline
• Dextrose(???)solution

• In Specific embodiment
• phosphate buffered saline
• buffered saline solution generally between the pH
  7.0-8.0 range
• water

17
Liquid Aerosol Formulation
They are useful for 1) pH maintenance 2) solution
stabilization 3) regulating osmotic pressure
solubilizing or emulsifying agents
excipients
surfactants
18
Liquid Aerosol Formulation
Benzodiazepine (???????)
narcotic analgesic (?????)
19
Aerosol Dry Powder Formulation
a dispersing agent
ketamine
a bulking agent (eg. lactose, sucrose)
20
Aerosol Dry Powder Formulation
Dispersing agent facilitates the dispersal of the
powder from the device
May include another therapeutically effective
drug like benzodiazepine and narcotic analgesic
21
Safety Tests

• According to several research and studies
• 1) tolerance and/or dependence to the drug
• 2) great deal in common with other drugs linked
• with dependence including stimulants,
• opiates, alcohol, and cannabis
• 3) indulges in excessive amounts over a short
• period of time

22
Human Trials

• The drug was first given to American soldiers
  during the Vietnam War.
• A 2-year prospective audit of sedation practice
  was undertaken by the Department of Emergency
  Medicine.

23
Test
Total people involved 210  
24
Results
Time/ min
25
Results
Percentage/
14.6
22.2
26
Results

1. Apnoea(??) and hypoxia(??) most often occurred
   with midazolam and propofol
2. hypertension(????) and hypertonicity(????)were
   encountered more frequently with ketamine
3. 19.5 of patients given ketamine suffered from
   the reemergence phenomenon.

27
Conclusion

• 1) Ketamine is both safe and effective
• 2) Ketamine compares favourably with
• midazolam as an agent for procedural
• sedation
• 3) Ketamine may be particularly useful in groups
• of patients at high risk of adverse effects
  with
• midazolam

28
Market Approval

• 1) In 1970, the FDA approved ketamine for
• human use
• 2) It was (and still is) legally sold as
• (i) Ketalar (Parke-Davis, for humans)
• (ii) Ketaset (For Dodge, for animals),
• (iii) other brands (like Ketamine
• Hydrochloride)