Advanced pharmaceutics

1. PRAPARED BY:- MAYURI SAWANT
First Year M.Pharm
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2. DEFINATION:-It is investigation of physical and chemical
property of drug substance alone & or when combined
with excipient.
OBJECTIVE:
To generate information useful to formulator in devoloping
Stable & safe dosage form with good bioavailability.
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3. DEFINATION:-
Solubility is defined as:-
 In Quantitative term the concentration of solute in saturated
solution at certain tempreture.
In Qualitative term it is sponteneous interaction of two or
more substance to form homogenous molecular dispersion.
IUPAC DEFINATION:-Solubility is Analytical composition Of
saturated solution expressed as a proportion of designated solute
in designated solvent.
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4. SATURATED SOLUTION:-Solute equilibrium with solid phase.
UNSATURATED SOLUTION:-Dissolved solute in concentration below
that necessary for complete saturation at a definite tempreture.
SUPERSATURATED SOLUTION:-more dissolved solute at definite
tempreture & undissolved solute present.
ABSOLUTE OR INTRINSIC SOLUBILITY:-Maximum amount of solute
Dissolve in given solvent under standard condition of tempreture,
Pressure & PH.
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5. TERM PARTS OF SOLVENT REQUIRED FOR
1 PART OF SOLUTE
Very soluble Less than 1 part
Freely Soluble 1 to 10parts
Soluble 10 to 30 parts
Sparingly Soluble 30 to 100 parts
Slightly Soluble 100 to 1000 parts
Very Slightly Soluble 1000 to 10000 parts
Practically Insoluble More than 10000 parts5

6. TEMPRETURE-
 1) For gases:-Tempreture increases,
solubility decrease.
2)For solid in liquid solubility:-
-Decrease in solubility with increase
temperature.(Exothermic reaction)
- Increase in solubility with increase
in in tempreture(Endothermic reaction)
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7. PRESSURE-
-For Gases:-Increase in solubility
with increase in pressure.
-Henry's Law states that: solubility of
g gas in a liquid is directly proportional
t to the pressure of that gas above the
s surface of the solution.
 PARTICAL SIZE -Solubility increase with
e decreasing size of solute particle
b because of the additional surface
e energy.
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8. PH:-
-Zn(OH)2 is a sparingly soluble base.
-Zn(OH)2(s)⇌Zn2+(aq)+2OH-(aq)
-If you increase the pH by adding OH- ions, Le Châtelier's Principle says
that the position of equilibrium will move to the left.
-The solubility of the Zn(OH)2 decreases.
-If you decrease the pH by adding H3O+ ions, the added H3O+ ions will
react with the OH- ions and form water.
-OH- ions are removed from solution.
-According to Le Châtelier's Principle, the position of equilibrium moves to
the right to replace the OH- ions.
-The solubility of the Zn(OH)2 increases.8

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10. Solubility of substance serve as standard test for purity.
The solubility of drug in GI fluid (dissolution)is important step for
better Absorption.
Side effect of drug are representative of poor aqueous solubility.
Extraction & recrystalisation process.
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11. Physical Modifications —
-Particle size reduction like micronization and nanosuspension,
modification of the crystal habit like polymorphs, amorphous form
and cocrystallization, drug dispersion in carriers like eutectic
mixtures, solid dispersions, solid solutions and cryogenic
techniques.
Chemical Modifications —
-Change of PH, use of buffer, derivatization, complexation, and
salt formation.
Miscellaneous Methods —
-Supercritical fluid process, use of adjuvant like surfactant,
solubilizers, cosolvency, hydrotrophy , and novel excipients.11
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DEFINATION: Ratio of unionized drug distributed between
organic (n-octanol) and aqueous (water) phase at equilibrium.
Ko/w = (Conc. of drug in organic phase/ Conc. of drug in water)
Partition Coefficient have no unit.
Hydrophobic drug HIGH Ko/w
Hydrophilic drug LOW Ko/w

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Henderson-Hasselbalch equations:
 -For acidic drugs:
pH = pKa + log [ionized drug]
[unionized drug]
 -For Basic Drug:
pH = pKa + log [unionized drug]
[ [ionized drug].
Defination:-pKa is the negative base-10 logarithm of the acid
dissociation constant (Ka) of a solution.
pKa = -log10Ka

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Dissolution is exothermic, the dissociation constant rise with
increasing temperature.
Dissolution is endothermic, the dissociation constant will fall with
increasing temperature.
Pka value tells us:-
1. Strength of acid &base
2. what a molecule will do at a specific pH.
3. what the pH needs to be in order for a chemical species to
donate or accept a proton.
The weaker the acid, the stronger the conjugate base.

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The lower the pKa value, stronger the acid.
For Ex:- the pKa of acetic acid is 4.8, while the pKa of lactic acid
is 3.8. Using the pKa values, one can see lactic acid is a stronger
acid than acetic acid.

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Its tells us ionised form & unionised form of drug
mean its Absorption of drug in systemic circulation.
Ex:-If Pka value of drug is equal to PH then the 50%
drug is in ionised form & 50% drug Is in Unionised
form.
Tells us its excretion rate of drug.

17. A.MARTIN,PHYSICAL PHARMACY,3rd eddition 1991,varghese
publishing house .
Allen, L. and Ansel, H. (2014). Ansel’s pharmaceutical Dosage
forms & Drug delivery systems (10th ed). Philadelphia: Lippincott
Williams & Wilkins.
Aulton M. E and Taylor M. (2013). Aulton’s Pharmaceutics: The
Design and Manufacture of Medicines. Amsterdam, Netherlands:
Churchill Livingstone Elsevier.
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