Transcript Physical & Chemical Factors that Affect`s Drug`s Biological

Physical & Chemical
Factors that Affect’s Drug’s
Biological Performance
Roselyn Aperocho-Naranjo
Pharmacy Instructor
USPF, College of Pharmacy
Particle Size
How does Particle size affects
drug absorption?
 The decreasing size of drug
particles will increase the
surface area of the drug &
will cause a rapid
dissolution rate in a
dissolution media.
Particle Size
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However, the solubility does not significantly
affect the particle size reduction or
micronization in the manufacture of
pharmaceutical agents.
Drug’s therapeutic effect depends on its
particle size:
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Amphotericin, aspirin, bishydroxycoumarin,
chloramphenicol, griseofulvin, digoxin, fluocinolone
acetonide, meprobamate, nitrofurantoin,
phenobarbital, phenothiazine, phenylbutazone,
prednisolone, penicillin, sulfadiazine, and tolbutamide.
Co-Solute & Complex Formation
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The co-solute formation is concerned only with drugs
having low solubility.
Processes of forming co-solute
water
compounds:
1. Salting-out
NaCl
Organic
nonelectrolyte
dissolved
Hydrated ions
Na
Cl
Precipitated organic
nonelectrolye
Co-Solute & Complex Formation
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The co-solute formation is concerned only with drug’s
having low solubility.
Processes of forming co-solute
compounds:
1. Salting-In
water
RCOOH
Organic salt/Acid
Or Salt of Ammonium
compounds
Undissolved organic electrolyte
dissolved organic
electrolyte
Co-Solute & Complex Formation
3. Clathrate Formation
Clathrate forming substances are:
 Gallic acid, urea, thiourea, amylose
and zeolite
Drugs used in dissolving clathrates are:
- Vitamin A, Sulfathiazole,
chloramphenicol & reserpine.
Co-Solute & Complex Formation
4. Solid-in Solid Solution Complex
- is formed when a melted solid
substance is mixed with another solid
such as mannitol dissolved in succinic
acid. These substances are rapidly
dissolved in water.
Chemical Variation
Made for two reasons:
1. change the strucutre of the active
compound to increase pharmacologic
response
2. maintain basic structure but the
solubility is changed by the formation of
either salts, ester, ether or other complex
compounds.
Chemical Variation
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Salt formation
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Electrolytes have higher solubility
More rapidly dissolved/faster dissolution rate
than free acids & free bases
In acidic drugs, dissolution rate increases with
increasing pH (salt formation)
• Esters
- drugs dissolves at higher pH in the
small intestines
- possess different rate of hydrolysis
Amorphous Crystalline Solids
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Is more stable and have higher dissolution
rate than the crystalline form
Example: PenG should not be used in
amorphous form because it is more
rapidly dissolved in the stomach fluid the
crystalline form.
Anhydrous Form, Hydrates
& Solvates
Hydrates – are additon compounds of
drugs with water
- dissolves more rapidly than the
crystalline form
Solvates – are addition compounds of drug
and organic solvent
- dissolves faster than the nonsolvated form
Polymorphism
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Drug exist in different forms
Exist only in a solid state
Highest form of stability but lowest
dissolution rate
When dissolution rate is high, stability is
low
Can be stabilized by adding viscosity
increasing agents
Viscosity
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Prolongs the diffusion time of solvent
molecules
Disintegration & dissolution of drugs in
tablet form is decreased with increasing
viscosity
Food increases the viscosity of GIT
content
Delay the absorption of drugs such as
ethanol, salicylic acid, sulfonamides
Solubilizing Agents
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Refers to Surface Active Agents (surfactants)
The drug possess a hydrophilic and a lipophilic
ends, these will associate with the solvent
molecule forming a colloidal solution
The associate ,molecules formed are called
micelles or aggregates
Critical Micelle Concentration contains 50 to
150 molecules
If drug concentration is below the CMC,
released rapidly
Solubilizing Agents
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If drug concentration is below the CMC,
released rapidly
If the CMC of the drug is high, drug
release is affected
Examples are drug that are not diluted
upon administration such as those given
topically, rectally, intramuscularly and
subcutaneous route
Solubilizing Agents
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Drugs may have an increased
bioavailability due to the surface active
agents added
Include vitamin A, riboflavin,
spironolactone and sulfisoxazole
Adsorption
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Is the tendency of the substance to
accumulate at a surface due to the
unbalanced forces that causes the
attraction of molecules on any surface.
Occur when the valence requirement of
the molecule is bonded to adjacent
molecules.
Adsorption
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These attraction between adjacent molecules
is called Van der waals force.
Adsorption & desorption occur rapidly
Chemisorption occur when the valence
requirements of surface molecule are not fully
met by the adjacent molecules.
Usually require heating to activate electron
transfer
Example: Charcoal is used as antidote due to its
adsorptive property.
Manufacturing Factors
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Increased tablet compression and
Increased amount of binders forced
increased hardness of tablets and may
prolong disintegration and dissolution
time.
Increased amount of lubricants decrease
hydrophilicity and wetting of tablets, also
prolong disintegration and dissolution
time
Manufacturing Factors
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Increased amount of heat will cause
suppositories to dissolve in the base which
when cooled down,, it will form crystals
and large needles thus prolonging the
drug release
Summary
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Different factors alter biological
performance of drugs such as the rate
and extent of drug release from the
dosage form upon administration
Drugs should be in aquoues form except
for rare cases of pinocytosis
Drug release can be determined in vitro
by dissolution rate test for peroral and
oral dosage forms and by dialysis for
rectal and topical preparations
Summary
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Drugs having different release
characteristic reslts in different blood
level curves in vivo
The difference in drug release is caused
by the rates of drug release rather than
the absorption pattern
Absorption rate is encountered in drugs
with low solubility
Prepare on whole sheet of paper
Answer the following questions:
How does the following factors affect the
release of drug from its original dosage
form and solubility?
A. Clathrates
B. Solid Amorphous Forms
C. Chemical Variation
D.