Faculty of Pharmaceutical Sciences
- PDM University (www.pdm.ac.in/pharmacy) Bahadurgarh, Delhi NCR -------------------------------------------------------------------------------------------------------------------------------------
B.Pharma 3rd Sem
BP302T
Physical Pharmacy (Theory)
Unit II (B): Physicochemical properties of Drug Molecules
Outline of the Chapter:
Topics 1. Refractive index 2. Optical rotation 3. Dielectric constant 4. Dipole moment 5. Dissociation constant
Deals with Definition, Measurements, Factors and Applications Definition, Measurements, Factors and Applications Definition, Measurements, Factors and Applications Definition, Measurements, Factors and Applications Definition, Measurements, Factors and Applications
To prepare the Document “Physical Pharmaceutics –I” by Dr. Shalini Sharma and Dr. Surajj Sarode’s was referred!
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________
PDM University Page | 2
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________
1. Refractive Index
PDM University Page | 3
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________ Measurement:
PDM University Page | 4 1. Abbe’s Refractometer
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________
PDM University Page | 5
2. Pulfrich Refractometer
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________ 3. Immersion Refractometer
PDM University Page | 6
4. V Block Refractometer
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________ Factors affecting on Refractive Index
PDM University Page | 7 Application of Refractive Index
Specific Refraction
Molecular Refraction
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________
2. Optical Rotation
PDM University Page | 8
ď ś Measurement
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________ Factors affecting on Optical Rotation 1. For a given compound, the extent and direction of this rotation depends on the orientation of the molecule in relation to the beam. 2. Direction of beam onto the molecule. 3. physical properties of crystal it is directly proportional 4. Thickness of crystal 5. Mass density of the crystal or concentration in the case of solutions. 6. Wavelength of light used 7. The temperature of the solutions. Applications
Specific Rotation
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
PDM University Page | 9
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________
3. Dielectric Constant PDM University Page | 10
Measurements
Factors The dielectric constant decreased with an increase in the dopant concentration due to second phase formation. Applications
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________
4. Dipole Moment
PDM University Page | 11
ď ś Measurements
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________ Factors 1. Polarity of molecule 2. Magnitude of charge 3. Geometry of molecule
Applications
PDM University Page | 12
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________
5. Dissociation constant
PDM University Page | 13
For this reaction Acid Dissociation constant ka will be:
pKa : pKa is the negative logarithm of the acid dissociation constant [Ka] of a weak acid; it is also the force that the molecules have when dissociating.
Henderson–Hasselbalch equation: The relationship between pH, pKa and extent of ionization is described by Henderson–Hasselbalch equation. Which is:
Alternatively
That is why during the determination of pka by applying Henderson–Hasselbalch equation half neutralization is done
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________ Percent Ionization:
PDM University Page | 14
Measurements pKa can be measured by using any one of the following methods: 1. Potentiometric titration, 2. Spectrophotometric methods, 3. NMR titration, 4. Liquid chromatography (LC), 5. Capillary electrophoresis (CE), 6. Combined methods, 7. Computational methods
Factors 1. Charge
2. The Role of the Atom
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________ 3. Resonance
PDM University Page | 15
4. Inductive effects
5. Orbitals
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________ Applications
PDM University Page | 16
What is the difference between pH and pKa? The main difference between pH and pKa is that pH tells the level of hydrogen ions in a certain medium while pKa value indicates the degree at which an acid dissociates or the side at which equilibrium is favored, Additionally, pKa is usually the logarithm of Ka value while pH is the inverse of H+ concentration logarithm.
pH and pKa can be related by Henderson Hasselbalch equation:
Where, pH is the scale of acidity pKa is the scale of dissociation constant.
Understanding Kb and pKb Kb is the base dissociation constant. The base dissociation constant is a measure of how completely a base dissociates into its component ions in water. Kb = [B+][OH-]/[BOH] pKb = -log Kb A large Kb value indicates the high level of dissociation of a strong base. A lower pKb value indicates a stronger base. pKa and pKb are related by the simple relation: pKa + pKb = 14 What Is pI? pI is the isoelectric point. It is the pH at which a protein (or another molecule) is electrically neutral (has no net electrical charge).
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________ Difference between pKa and Partition co-efficient
pKa or 'Dissociation Constant The pKa or 'Dissociation Constant' is a measure of the strength of an acid or a base. The pKa allows you to determine the charge on a molecule at any given pH. High value indicates weak acid and low pKa indicates strong acid
Partition Coefficient (LogP) The Partition Coefficient (LogP) is a measure of how well a substance partitions between a lipid (oil) and water. If partition coefficient of drug is more than one it is more lipophilic and If the partition coefficient of drug is less than one it is less lipophilic.
pKa Table The proper use of a pKa table to find the ability to recognize which acid-base reactions will happen and which will not!
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
PDM University Page | 17
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________
PDM University Page | 18
Suggested Books For Reading: Physical Pharmacy by Alfred Martin Tutorial Pharmacy by Cooper and Gunn. Physical Pharmaceutics by C.V.S. Subramanyam
Physical Pharmaceutics by Ramasamy C and ManavalanR. Test book of Physical Phramacy, by Gaurav Jain & Roop K. Khar
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________
PDM University Page | 19
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)
Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)
___________________________________________________________________________ For any Quarries please contact: Prof. Hema Chaudhury, Dean of Faculty of Pharmaceutical Sciences, PDM University (Email: principal_cop@pdm.ac.in, hema_manan@rediffmail.com )
Abhijit Debnath, Asst Professor, Faculty of Pharmaceutical Sciences, PDM University (Email: theabhijitdn@gmail.com )
PDM University Page | 20
_________________________________________________________________________________ From the desk of Abhijit Debnath, Asst. Professor PDM University (B.Pharma, M.Pharma, O-level, NPTEL Introduction to Research (IIT-Madras), Health Research Fundamentals (National Institute of Epidemiology), Functional Genomics (IIT Kanpur), Biomedical Nanotechnology (IIT Roorkee), Human Molecular Genetics( IIT Kanpur, Biochemistry (IIT Kharagpur)