PHYSICO-CHEMICAL PROPERTIES OF
DRUGS
Physical Chemical
Solubility and Permeability Partition Coefficient
Physical State Isomerism
Polarity Intermolecular Forces
Particle Size Ionization
Melting Point pH
Functional Group
QUESTIONS
1. What are the requirements for a drug to exert
its biological effect?
The Drug must:
pass through barriers
survive alternate sites of attachment/storage
avoid metabolic destruction before it reaches the site
of action
allow favorable binding characteristics
dissociate from receptor and reenter the systemic
circulation to be excreted
QUESTIONS
2. What route of administration will give fast drug
action?
Intravenous (IV) route of administration
QUESTIONS
3. What are the different forces involved in drug-
receptor interaction? Explain.
Covalent Bonds bond formed by sharing electrons
between atoms
Ionic
Bonds bond formed by the attraction between
atoms of opposite charge
Hydrogen Bonds bond formed by hydrogen atoms
bound to electronegative atoms
QUESTIONS
3. What are the different forces involved in drug-
receptor interaction? Explain.
Ion-Dipole bond formed from the electrostatic
attraction between an ion and a neutral molecule that
has a dipole.
Dipole-Dipole bond formed between the positive end
of one polar molecule and the negative end of another
polar molecule
Van der waals forces bond formed when any two
uncharged atoms approach each other very closely
QUESTIONS
4. What form of drug is well absorbed and excreted
in the body?
Intravenous (IV) route of administration
QUESTIONS
5. What is the importance of a drug receptor?
What is the principle of Drug-Receptor
Interaction?
RECEPTO DRUG-RECEPTOR
DRUG R COMPLEX
PHARMACOLOGICA
L EFFECT
BIOTRANSFORMATION REACTIONS
Phase 1 Functionalization Phase 2 Conjugation
Reactions Reactions
Glucuronic Acid
Conjugation
Oxidative Reactions Sulfate Conjugation
Reductive Reactions Amino Acid
Hydrolytic Reactions Conjugation
Acetylation
Methylation
QUESTIONS
1. What is Biotransformation?
Biotransformation is the conversion of
lipophilic chemicals into more hydrophilic
(water-soluble) derivatives to be readily
eliminated in urine or bile.
QUESTIONS
2. What are the different sites of drug biotransformation?
Liver MAIN SITE
Intestinal Mucosa orally administered drugs
Kidney
Lungs
Placenta
Substrate selective and limited to
Brain Particular types of reactions
Adrenal glands
Skin
QUESTIONS
3. Identify the different factors affecting
drug metabolism. Explain the effect
Age Differences
Species and Strain Differences
Hereditary or Genetic Factors
Sex Differences
Enzyme Induction and Inhibition
Miscellaneous Factors
QUESTIONS
4. Are drug metabolites pharmacologically active or
inactive? Explain and give examples
Active or Inactive Parent compounds when administered must
be metabolically converted to biologically ACTIVE drugs
(metabolites)
e.g. Phenacetin (Analgesic) Acetaminophen
Active Parent Active Metabolite
Azathioprine (Immunosuppresant) 6-Mercapturine
Inactive Parent Active Metabolite
QUESTIONS
5. Which of the two phases of drug
metabolism produces water soluble and
readily excretable metabolites?
Phase II or Conjugation metabolism
*Phase I reactions MAY NOT produce sufficiently
hydrophilic and readily excretable metabolites
OTHER METHOD
Sodium salicylateis by treated
withsodium phenolate withcarbon
dioxideat high pressure (100 atm) and
high temperature (390K) -a method known
as theKolbe-Schmitt reaction.
CHEMICAL FORMULA
Salicylic acid C7H6O3
Me Salicylate C8H8O3
Sodium Hydroxide NaOH
Hydrochloric acid HCl
CHEMICAL REACTIONS
THEORETICAL YIELD
DENSITY Volume Mass MW
2.13 g/ mL 200 mL =
1.17 g/ mL 10 mL=
TY=( MW of the Product) ( Wgt Reactants)
MW of the Reactants
SOLUTION FOR THEORETICAL
YIELD
TY=( MW of the Product) ( Wgt Reactants)
MW of the Reactants
% YIELD
Percent Yield= Actual Yield X 100
Theoretical Yield
Eg. Actual yield: 3 g
PHYSICAL PROPERTIES
Color = white
Odor = odorless
Appearance = crystalline powder
Melting Point = 158-161 C
CHEMICAL PROPERTIES
Reagents Result
Bromine water white ppt
(Tribromophenol- bromide)
Ferric Chloride soln Violet solution
Methyl Alcohol Irritating/ pungent odor
(forms and ester and water)
CONCLUSION
Salicylic acid can be done..
It has it own physical and chemical properties.
ANSWERS TO QUESTIONS
1. What chemical group can you attribute the
color change of salicylic acid with Ferric
chloride soln?
Phenol group = monohydroxybenzoic acid
+ purple, blue, red or green color
STRUCTURE OF SA
Me Salicylate
Aspirin
ANSWERS TO QUESTIONS
2. What are the pharmaceutical and medicinal uses
of salicylic acid?
Anti-septic pain reliever
Keratolytic Fever Relief
Anti-fungal
ANSWERS TO QUESTIONS
3. What is the difference between natural and
synthetic salicylic acid?
Natural SA (wintergreen leaves, sweet birch
bark, willow bark)
Synthetic SA (synthesize in the lab)
+ Natural SA does not have negative effects
ANSWERS TO QUESTIONS
4. What are the major chemical classes of
salicylates in medicine?
USES
Salicylic acid = keratolytic/ antiseptic
Sodium salicylate = analgesic/
antipyretic
Acetyl SA = analgesic/ antipyretic
Me Salicylate = liniment
ANSWERS TO QUESTIONS
5. What pharmacologic category do drugs
containing SA belong to?
Salicylates = NSAID
METABOLISM OF SA
SA glucosyltransferaseconverts SA to
Its metabolite SA glucoside.
SYNTHESIS OF ACETYLSALICYLIC
ACID
3 g of Salicylic acid + 6 mL acetic anhydride
+ 85% phosphoric acid
Heat 10 mins in beaker
Distilled water
+ 20 mL water then COOL
Scratch the walls of the flask, filter, wash
The crystals, filter, then oven dry
WEIGH
CHEMICAL FORMULA
Salicylic acid - C7H6O3
Acetic anhydride - C4H6O3
Phosphoric acid - H3PO4
Ferric Chloride - FeCl3
Sodium hydroxide - NaOH
Sulfuric acid - H2SO4
Acetic Acid
Acetylsalicylic acid
CHEMICAL REACTION
THEORETICAL YIELD
DENSITY Volume Mass MW
SA 1.443 g/cm3 3g
Acetic 1.082 g cm3 6 mL
TY=( MW of the Product) ( Wgt Reactants)
MW of the Reactants
SOLUTION FOR THEORETICAL
YIELD
TY=( MW of the Product) ( Wgt Reactants)
MW of the Reactants
= _____?
PERCENT YIELD
Percent Yield= Actual Yield X 100
Theoretical Yield
Eg. Actual yield: 2.5 g
=
= ___?
PHYSICAL PROPERTIES
Color = white
Odor = odorless
Appearance = crystal figures
Melting point = 135C
CHEMICAL PROPERTIES
Reagents Result
Ferric Chloride Violet colored soln
Sodium hydroxide Yield water and
Na salicylate
Ethanol, sulfuric acid Yield water and
Me Salicylate
CHEMICAL REACTION
IN CONCLUSION:
Acetylsalicylic acid can be done..
It has it own physical and chemical properties.
STRUCTURE OF ASA
ANSWERS TO QUESTIONS
1. Give the products of Aspirin hydrolysis.
ANSWERS TO QUESTIONS
2. Why is the salt form used in place of the original
acetsalicylic acid in dosage from formulation?
- Salts of ASA are unstable in pharmaceutical
dosage forms.
ANSWERS TO QUESTIONS
3. Give the different therapeutic uses of
acetylsalicylic acid?
NSAID indicated for fever and pain (RA, Reiters
syndrome, Osteoarthritis) and inflammation in
the body.
Prevents blood clots (stroke to occur, heart
attacks)
ANSWERS TO QUESTIONS
4. What are the side effects of acetylsalicylic acid?
Gastrointestinal effects (stomach ulcerations,
abdominal burning, pain, cramps, nausea,
gastritis and bleeding)
Tinnitus
Liver toxicity
Others: Rash, vertigo, dizziness, kidney
impairment.
ANSWERS TO QUESTIONS
5. What are the conditions that lead to gastric
mucosal irritation of acetylsalcylic acid?
Alcohol intake
Corticosteroids
Pyrazolone derivatives (phenylbutazone)
Ibuprofen
ANSWERS TO QUESTIONS
6. What is the storage requirement for salicylic
acid?
Store at room temperatue.
Away from moisture and light
Do not use if ASA has vinegar smell.
METABOLISM OF
ACETYLSALICYLIC ACID
Glucuronidation
Active metabolite : Salicylate
SYNTHESIS OF METHYL
SALICYLATE
60 mL methanol + 27.6 Salicylic acid
H2SO4, swirl
reflux 2 hrs
cool in iced bath
20% sodium carbonate
(50 ml of hexane, 5 minutes)
SYNTHESIS OF METHYL
SALICYLATE
Drain off the aqueous layer from funnel
Wash hexane soln with
Water, drain soln contain
Sodium salt of SA
Dry hexane soln with Mg sulfate
Then, evaporate in fume hood
CHEMICAL FORMULA
Salicylic acid - C7H6O3
Methanol - CH3OH
Hydrochloric acid - HCl
Hexane - C6H14
Magnesium SO4 - MgSO4
Sulfuric acid - H2SO4
Ferric Chloride - FeCl3
Me Salicylate -
CHEMICAL REACTION
CHEMICAL REACTION
THEORETICAL YIELD
DENSITY Volume Mass MW
SA 1.44 g/cm 3g
Acetic 1.08 g/cm 6mL
ASA 1.40 g/cm
TY=( MW of the Product) ( Wgt Reactants)
MW of the Reactants
SOLUTION FOR THEORETICAL
YIELD
TY=( MW of the Product) ( Wgt Reactants)
MW of the Reactants
= _____?
PERCENT YIELD
Percent Yield= Actual Yield X 100
Theoretical Yield
Eg. Actual yield: 20 g
=
= ___?
PHYSICAL PROPERTIES
Color = white
Odor = odorless
Appearance = crystalline powder
Melting Point = 135 C
CHEMICAL PROPERTIES
Reagents Result
Ferric Chloride Violet colored soln
Sodium hydroxideYields water and
Na salicylate
Ethanol, H2SO4 Yields water and Me
salicylate
STRUCTURAL OF METHYL SA
ANSWERS TO QUESTIONS:
1. What is the mechanism of methyl salicylate
formation?
Carboxylic acid + alcohol = ester & water.
ANSWERS TO QUESTIONS:
2. What are the natural sources of methyl
salicylate?
Pyrotaceae Family, Pyrola genus
, Gaultheria genus
Wintergreen
ANSWERS TO QUESTIONS:
3. What method is used in the extraction of methyl
salicylate from plants?
Steam distillation to extract essential oils
Wintergreen is purified thru application of steam.
Maceration is performed to isolate the essential oil
(Me Salicylate)
ANSWERS TO QUESTIONS:
4. What is the use of methyl salicylate? Give
examples of its preparation available in the
market?
Rubefacient in deep heating liniments.
Flavoring agents
Odor masking agent
ANSWERS TO QUESTIONS:
6. Why is the internal use of methyl salicylate
limited to small quantities only?
Can induce vomiting
Severe fetal poisoning
Symptoms: tinnitus, NV, swelling, convulsion,
kidney failure, dizziness, drowsiness and fever.
