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Physico-Chemical Properties of The Drug Affecting Bioavailability
Physico-Chemical Properties of The Drug Affecting Bioavailability
Affecting Bioavailability
=dissolution rate
D=diffusion coefficient
A=surface area
V=volume of dissolution
h=thickness of stagnant layer
K=dissoltion rate constant
Cs=concentration in stagnant layer
Cb=concentration in the bulk (time t)
Theories of drug dissolution
1. Method of granulation
– Duration of blending, time and temperature of drying
– Formation of crystal bridge by the presence of liquid
– The liquid act as chemical reactions such as hydrolysis
– The drying step may harm the thermolabile drugs
2. Compression force
– Influence density, porosity, hardness, disintegration time,
and dissolution of tablets
The nature of the excipients in the drug product
1) Excipients are pharmacodynamically inactive
substances that are added to a formulation to provide
certain functional properties to the drug and dosage
form.
2) it should be inert, inactive, neither enhances nor
diminishes the therapeutic effect of the drug
3) Role/effects of excipient
a. may affect drug absorption
b. may increase solubility
c. may increase retention time of drug in the GIT
d. may act as carriers to increase diffusion across intestinal wall
Different Excipients used in Tablets
1. Diluents – added to increase the bulk/mass of the
dosage form
ex. Lactose, Dibasic Ca Phosphate, starch,
microcrystalline cellulose
2. Binder – makes the diluent adhere to the tablet to
form a compact mass. Pressure is applied to make
the tablets contact.
Ex. Acacia, alginic acid, gelatin, povidone, etc.
Different Excipients used in Tablets
• 3. Lubricant
– helps to have an easier transfer from one stage of
manufacture to another
– assist the smooth tableting process.
Ex. Mag. Stearate, stearic acid, talc, hydrogenated
vegetable oil
excessive magnesium stearate (a hydrophobic lubricant) in
the formulation may retard drug dissolution and cause
slower drug absorption.
Different Excipients used in Tablets
4. Disintegrants
• a decrease in the amount of disintegrant can
significantly lower bioavailability.
• Adsorbent disintegrants like bentonite and veegum
should be avoided with low dose.
• MCC (disintegrants and binder) at high compression
forces may retard drug dissolution.
Different Excipients used in Tablets
5. Tablet Coating
protection
uneven coating can cause uneven release of active
ingredient
• Example:
an enteric coatings – employed to permit safe passage
of tablet through the acid environment of the stomach
where certain drugs may be destroyed, to the more
suitable juices of the intestines where tablet dissolution
safely takes place. ( shellac, cellulose acetate phthalate)
• b. film-coatings
employed to protect the drug substance from the
destructive influences of moisture, light and air
throughout their period of storage or to conceal a
bad or bitter taste from the taste buds of the patient.
(hydroxypropylmethylcellulose).
c. sugar-coatings – conceal bitter taste (liquid glucose,
sucrose)
Excipient Used in Liquid Dosage Form
1. Vehicle (solvent)
bioavailability of a drug from vehicles depend to a
large extent on its miscibility with biolgical fluids.
Viscosity is another factor
– Aqueous vehicles
– Non aqueous water miscible vehicles
– Non aqueous water immiscible vehicles
Excipient Used in Liquid Dosage Form
3. Surfactants
mechanism of surfactant increase an absorption:
Promotion of wetting
Better membrane contact
Enhanced membrane permeability
Decreased absorption by surfactant due to:
Formation of unabsorbable complex
Laxative action
Excipient Used in Liquid Dosage Form
4. Buffers
useful in creating the right atmosphere for drug
dissolution
Excipient Used in Liquid Dosage Form
5. Complexing agent
alter stability, solubility, molecular size, partition
coefficient, diffusion coefficient.
complexation used to enhance drug bioavailability:
Enhanced dissolution
Enhanced lipophilicity
Enhanced membran permeability
complexation reduce drug availability:
formation of poorly soluble or poorly absorbable complex
Excipient Used in Liquid Dosage Form
6. Colorants
inhibit dissolution (ex:brillian blue-sulfathiazole)
Inhibit miscellar solubilization
Cationic dyes more reactive due to greater power for
adsorption
Excipient Used in Liquid Dosage Form