SOLUBILITY

Kuncoro Foe
 REFERENCES
 Martin, Physical Pharmacy
 Remington’s Pharmaceutical Science
 Sprowl, Prescription Pharmacy
 Husa’s Dispensing of Medication
 Burlage, Physical Pharmacy
 Lachman, Industrial Pharmacy
 Scoville
 Solubility Phenomena
 Kelarutan suatu elektrolit lemah
 Pengaruh pH terhadap kelarutan elektrolit
lemah
 Pengaruh pelarut terhadap kelarutan obat
 Pengaruh kombinasi pH dan pelarut
terhadap kelarutan obat
 Pengaruh ukuran partikel terhadap
kelarutan
Campuran 2 Zat atau Lebih
 Solut
 Solven
 Sistem homogen:
 Satu fase
 True solution

 Sistem heterogen
 Lebih dari satu fase
 Colloidal solution
 Coarse dispersion
 Klasifikasi Sistem Dispersi
 Berdasarkan ukuran partikel (Kimia Fisik):
 Larutan  homogen
 Koloidal  heterogen
 Suspensi  heterogen

 Berdasarkan bentuk sediaan (Farmasetik):

 Larutan  homogen
 Emulsi  koloidal / kasar (heterogen)
 Suspensi  koloidal / kasar (heterogen)
 Kelarutan (1)
 Definisi:
1 bagian bobot zat padat / 1 bagian volume
zat cair larut dalam bagian volume tertentu
pelarut (20C)
 Konsentrasi solut dalam keseimbangan
dengan fase padat / larutan jenuh pada
suhu tertentu
 Interaksi spontan antara 2 atau lebih bahan
untuk membentuk suatu dispersi molekular
yang homogen
 Kelarutan (2)
 Sistem dispersi zat yang berwujud
padat, cair, gas: ada 9 macam kombinasi
 dapat membentuk dispersi molekular,
koloidal, kasar
 Larutan tak jenuh (unsaturated,
subsaturated): konsentrasi solut 
konsentrasi larutan jenuh
 Larutan lewat jenuh (supersaturated):
konsentrasi solut  konsentrasi larutan
jenuh
 Basic Principles
 Saturated solution
 Unsaturated or subsaturated solution
 Supersaturated solution
 Solubility in qualitative term
 Solubility in quantitative term:
quantitative expressions
 Solubility determination
 Solubility Expressions (1)
 Bilangan kelarutan didasarkan atas rasio
solut – solven yang pasti / eksak
1 : 10 m
 1 = 10 M
 % b/b X
 % b/v
 % v/v
N
 Solubility Expressions (2)
 Bilangan kelarutannya tidak pasti / non
eksak (nilai dalam rentang)
 Sangat mudah larut
 Mudah larut
 Larut
 Agak sukar larut
 Sukar larut
 Sangat sukar larut
 Praktis tidak larut
Solubility Determination (1)
 Constant condition:
 Temperature
 Stirring rate
 One variable: saturation time
 Instrument:
 Thermostat
 Millipore membrane filter
Solubility Determination (2)
 Theory of Solubility
 Polarity (Like Dissolves Like)
 Dielectric constant (Like Dissolves Like)
 Association (hydrogen bonding)
 Solvation
 Acid base reaction
 Internal pressure

Solubility depends on the molecular structure, chemical

and electrical properties of a solute and a solvent
Association by Hydrogen Bond
 Type of Solvents
 Polar: degree of polarity, hydrogen
bonding, high dielectric constant,
chemical reaction, dipole moment
 Non-polar: ‘like dissolves like’, low
dielectric constant, aprotic solvent,
no hydrogen bonding, weak van der
Waals-London forces
 Semi-polar, as an intermediate
solvent (ternary diagram phase)
 Polar Solvent
 Dielectric constant of water is high (80)
 Dapat menurunkan ‘force of attraction’
antar muatan elektrik yang berlawanan
dalam kristal
 Dapat memecah ikatan kovalen elektrolit
kuat melalui reaksi asam-basa
 Mampu melarutkan molekul dan ion
karena interaksi daya dipol
 Non Polar Solvent
 Dielectric constant of non polar solvent is
low (chloroform = 3, benzen = 2)
 Aprotic: tidak dapat memecah ikatan
kovalen dan tidak mengionisasi elektrolit
lemah
 Tidak dapat membentuk ikatan hidrogen
dengan non-elektrolit
 Dapat melarutkan senyawa non polar
karena interaksi induksi dipol (weak van
der Waals-London force)
 Semi Polar Solvent
 Dapat menaikkan derajat polaritas dari
pelarut non polar
 Sebagai ‘intermediate solvent’ agar
cairan polar dan non polar dapat
bercampur dengan cara menginduksi
pelarut polar menjadi non polar
 Diagram tiga fase (sistem tiga
komponen), contoh: air, peppermint oil,
polietilenglikol
Diagram Tiga Fase
Solubility of Gas in Liquid (1)
 Henry Law
 Effect of temperature and pressure
on the solubility of gas in liquid
 Salting-out
 Chemical reaction
 Solubility calculation
Solubility of Gas in Liquid (2)
 Solubility of Liquid in Liquid
 Ideal solution
 Real solution
 Raoult law
 Internal pressure
 Polar liquid: high internal pressure due
to high cohesion forces
 Less polar liquid: low internal pressure
 Partial miscibility
 Complete miscibility
Solubility of Solid in Liquid (1)
 Ideal solution
 Non-ideal solution, involving activity
coefficient
 Thermodynamic calculation
 Mechanism of dissolution of a solute
in a solvent
 Solvation and association of a polar
compound in a solution
Solubility of Solid in Liquid (2)
 In ideal solution, depends on:
 Temperature
 Meltingpoint of solid
 Molar heat of fusion ( Hf)
 Mechanism of Solubility (1)
 Molecule escapes from the solute phase
 Mechanism of Solubility (2)
 Creation of a hole in the solvent phase
 Mechanism of Solubility (3)
 Solute molecule enters into the hole of
solvent phase
Solubility Calculation in Two
Different Temperatures
 Solubility of Salt in Water (1)

 Influence of temperature
 Endothermic and exothermic processes
 Influence of pH on the solubility of weak
acid or weak base
 Influence of solvent on drug solubility
 Effect of combination of pH and solvent
 Effect of particle size
Solubility of Salt in Water (2)
Solubility of Weak Acid
Influence of pH on the Solubility
of Weak Acid
Solubility of Weak Base
Influence of pH on the Solubility
of Weak Base
Solubility Enhancement
 Alteration of pH
 Complex formation
 Multiple solvent
 Solubilizing agent
 Selection of polar/non-polar
compounds
 Size reduction
Influence of Solvent on
Drug Solubility
Influence of the Combination of
pH and Solvent
Influence of Particle Size on
Drug Solubility
Phenobarbital solubility (% w/v) in
alcohol – glycerol – water system
(25  0.1ºC)
Thank You

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