Physical Pharmacy- 3rd Sem- Unit 2B

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)

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_________________________________________________________________________________ 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)

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1. Refractive Index

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_________________________________________________________________________________ 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)

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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

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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)

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2. Optical Rotation

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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)

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Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)

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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)

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4. Dipole Moment

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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

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_________________________________________________________________________________ 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)

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5. Dissociation constant

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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:

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 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

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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

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 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 

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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

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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)

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Faculty of Pharmaceutical Sciences, PDM University (www.pdm.ac.in/pharmacy)

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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)

___________________________________________________________________________

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_________________________________________________________________________________ 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 )

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Abhijit Debnath, Asst Professor, Faculty of Pharmaceutical Sciences, PDM University (Email: theabhijitdn@gmail.com )

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_________________________________________________________________________________ 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)