This document provides information on pharmaceutical pre-formulation. It discusses parameters that are studied during pre-formulation including solubility, ionization constants, particle size and polymorphism. The goals of pre-formulation are to develop stable and bioavailable dosage forms that can be produced on a large scale. Understanding these physicochemical properties helps in the rational development and selection of appropriate dosage forms.
Solubility & distribution phenomenon is useful for pharmacy student to understand the concept on solubility & distribution when study the physical pharmacy.
This above presentation gives us complete information about solubility, reasons for determining solubility, types of solubility, pre-formulation solubility studies, determination of solubility, and analytical methods for solubility.
The solubility of a substance refers to the amount of substance that passes into the solution to achieve a saturated solution at constant temperature and pressure.
Solubility & distribution phenomenon is useful for pharmacy student to understand the concept on solubility & distribution when study the physical pharmacy.
This above presentation gives us complete information about solubility, reasons for determining solubility, types of solubility, pre-formulation solubility studies, determination of solubility, and analytical methods for solubility.
The solubility of a substance refers to the amount of substance that passes into the solution to achieve a saturated solution at constant temperature and pressure.
Biopharmaceutic considerations in Drug Product DesignRiaz Islam
Drug product Design remain one of the most challenging aspects in formulation development. But nowadays formulation strategies have been far more successful in improving the bioavailability of the compounds with poor solubility, poor dissolution rate, and poor chemical stability in acidic environment. This article begins with a brief discussion on Physical and Chemical Properties of the Drug Impacting Oral Absorption. This article also reviews the Factors Contributing to Poor Aqueous Solubility. and a brief relationship between Physicochemical Properties and Drug Delivery System.
Phase solubility analysis and pH solubility profileMohit Angolkar
A Brief presentation on the topic- phase solubility analysis and pH solubility profile, which covers the following aspects:
- Solubility introduction
- importance of solubility
- factors influencing solubility
- Phase solubility analysis introduction
- method of analysis
- purification technique
- introduction to pH solubility profile.
Qualitative analysis of inorganic salts, Identification of anions and cations,Conversion of different water insoluble or sparingly soluble substances into water soluble form.
Name of the Experiment: Manufacture of Aluminium Hydroxide Gel from the supplied material.
Qualitative analysis (identification) of anions from inorganic salt solutions.
Qualitative analysis (identification) of group I & group II cations.
Qualitative analysis (identification) of group III cation.
Qualitative analysis (identification) of group IV & group V cations.
How to test the Ammonium with Litmus paper?
How to Clean a Platinum Wire?
What is Qualitative Analysis?
solubility enhancement and cosolvency by madhavishaikhazaroddin
“cosolvency and soluility enhancement” Pharmatech 2003, 160-166. They had developed simultaneous determination of sitagliptin phospate monohydrate and metformin by ultra performance liquid chromatographic (uplc)method.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Biopharmaceutic considerations in Drug Product DesignRiaz Islam
Drug product Design remain one of the most challenging aspects in formulation development. But nowadays formulation strategies have been far more successful in improving the bioavailability of the compounds with poor solubility, poor dissolution rate, and poor chemical stability in acidic environment. This article begins with a brief discussion on Physical and Chemical Properties of the Drug Impacting Oral Absorption. This article also reviews the Factors Contributing to Poor Aqueous Solubility. and a brief relationship between Physicochemical Properties and Drug Delivery System.
Phase solubility analysis and pH solubility profileMohit Angolkar
A Brief presentation on the topic- phase solubility analysis and pH solubility profile, which covers the following aspects:
- Solubility introduction
- importance of solubility
- factors influencing solubility
- Phase solubility analysis introduction
- method of analysis
- purification technique
- introduction to pH solubility profile.
Qualitative analysis of inorganic salts, Identification of anions and cations,Conversion of different water insoluble or sparingly soluble substances into water soluble form.
Name of the Experiment: Manufacture of Aluminium Hydroxide Gel from the supplied material.
Qualitative analysis (identification) of anions from inorganic salt solutions.
Qualitative analysis (identification) of group I & group II cations.
Qualitative analysis (identification) of group III cation.
Qualitative analysis (identification) of group IV & group V cations.
How to test the Ammonium with Litmus paper?
How to Clean a Platinum Wire?
What is Qualitative Analysis?
solubility enhancement and cosolvency by madhavishaikhazaroddin
“cosolvency and soluility enhancement” Pharmatech 2003, 160-166. They had developed simultaneous determination of sitagliptin phospate monohydrate and metformin by ultra performance liquid chromatographic (uplc)method.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
The hemodynamic and autonomic determinants of elevated blood pressure in obes...
Preformulation 2020 Sakai.ppt
1. Pharmaceutical pre-formulation
Fakhrul Ahsan, Ph.D.
Office: Room # 214
fakhrul.ahsan@ttuhsc.edu
I have used the above book, Pharmaceutical dosage forms: Tablets Volume 1 by
Lieberman et al. I may have used sentences directly the book. A large number of
pictures used in this note are from various websites, which I did not cite to avoid
clutters.
2. Learning objectives
1. Understand pharmaceutical formulations and pre-formulations
2. Appreciate the roles of various physicochemical parameters in
dosage form development.
3. Define and understand the following parameters:
Solubility
PKa
Partition coefficient
Dissolution
Polymorphism
Drug stability
Particle size, shape and surface area
Flow properties
Compression properties
Compatibility with excipients
Hygroscopicity
4. Pharmaceutical formulations
A recipe or formula for a dosage form that
includes the following information
Name and quantities ingredients
Sequence of mixing the ingredients
Processing steps
A recipe for preparation of a drug product is
called formulation.
A Pharmaceutical formulation contains
One or more active ingredient (Drug)
Many additives called excipients
5. Pharmaceutical pre-formulation
Study the physical and chemical properties of a
drug substance alone and in combination with
excipients.
The first step in the rational development of
dosage forms of a drug substance.
Help develop stable and bioavailable dosage
forms that can be produced in large amount.
You start pre-formulation after biological
screening and when you decide for moving
forward to clinical trials
6. Pre-formulation parameters
Organoleptic Properties
Purity
Drug stability
Particle size, shape and
surface area
Solubility
pH-solubility profile
Solubilization
Dissolution
Partition coefficients
Ionization constant
Permeation across biological
membrane
Crystal properties and
polymorphism
Stability in the presence of
excipients
Density
Hygroscopicity
Flowability
Compactibility
Wettability
Potential hazards associated
with handling
7. Organoleptic properties
These parameters can be perceived
by sense organ:
Color
Odor
Taste
Drug substances, in general, have characteristics color,
odor and taste.
In pre-formulation step, you determine the organoleptic
properties.
In case of unacceptable tastes and odors, you add
flavors and excipients
You can add dyes to alleviate the unsightly and variable
color.
8. How do we test the taste?
Electronic tongue
A sensor device that can recognize, identify, and
discriminate tastes and flavors of various liquids
http://www.electronictongue.com/stand.html
9. Purity
The presence of unwanted substances is not
desirable.
Common impurities are
Metals:
Even a few parts per million may cause deleterious
effects on the dosage form.
Synthetic intermediates:
Maybe toxic or may not have therapeutic effects
Slight impurity may affect the appearance of the
drug substance
10. Solubility
The concentration of a solute in
a saturated solution at a certain
temperature.
Solubility affects
Bioavailability,
Drug release rate
Therapeutic efficacy.
Determination of solubility
Prepare a solution of the
material in a solvent by
adding an excess of the
material
Shake the solution until an
equilibrium is established
Quantitate the drug using an
analytical method
11. Solubilization
The process that increases the solubility
You can increase the solubility by adding a third
substance to the aqueous solution of a drug.
Common solubilizers
Organic solvents
Surfactants
Complexing agents.
Need for solubilization
If a drug has a solubility of 5 g/L, the dose is 500
mg, how much water would you need to solubilize a
single dose of the drug?
We will need 100,000 liter water to solubilize this
drug
Or we have to use other agents to solubilize the
drug.
The water volume of a pool 60 ft. long, 30 ft. wide and that slopes in depth from 3 ft. to 10 ft. is as
follows: 30 x 60 x ((10 + 3)/2) = 11,700 cubic ft. of water 11,700 x 7.5 = 87,750 gallons. =332,170 liters
12. pH-solubility profiles
Solubility of acidic and
basic compounds depend
on the pH of the medium
The solubility of a
compound is the sum of
the solubility of ionized
and unionized forms
An acidic compound is
more soluble in a basic
solvent
A basic compound is more
soluble in an acidic
solvent.
pH
Log
solubility
µmol/L)
Amphoteric drug
Basic drug
Acidic
drug
13. Ionization constant
The equilibrium constant for the reaction in which a
weak acid or base is in equilibrium with its
conjugate base or acid in aqueous solution.
Kb is the ionization constant of a base
Ka is the ionization constant of an acid
pKa = -log Ka
The smaller the pKa, the stronger the acid,
The Henderson-Hasselbalch equation can estimate
the ionized and un-ionized drug concentration at a
particular pH.
For acidic compounds:
pH = pKa + log ([ionized drug]/[un-ionized drug])
For basic compounds:
pH = pKa + log ([un-ionized drug]/[ionized drug])
14. Ionization constant
Drug stability
Drug instability may result from the gain or loss of a
proton by a substrate molecule
An electronic rearrangement may reduce or increase the
reactivity of the molecule
Drug activity
Weakly acidic or basic drugs may exist in ionized or non-
ionized form or in a mixture of both.
Drug absorption
Absorption of a many of drugs depends on the ionization
constants.
Non-ionized form of an acidic or basic drugs are soluble in
lipids and better absorbed via the lipoidal biological
membrane.
Completely ionized drugs are absorbed poorly.
15. Let’s take the poll
►Solubility is an organoleptic property (T/F).
►Solubility of an acidic drug increases with the
increase in pH of the solution (T/F).
►Ionized form of a drug is likely to be better
absorbed from the GI tract.
►To solubilize a drug, we prepare a drug solution
using as much water as we need (T/F).
16. Dissolution
The act of dissolving a
drug in a solvent or
biological fluid
The rate of dissolution is
the rate at which a solid
dissolves into a solvent
You can assess the extent
of absorption (In vitro) of
drugs from dosage forms
such as tablets and
capsules
Low dissolution means
(usually) poor absorption
Dissolution is the rate
limiting step for
absorption of poorly
soluble drug.
Used as a surrogate for
bioavailability
17. Dissolution assay
You place tablets or capsules
in a stainless steel wire
basket
You rotate the basket at a
fixed speed
Put the basket in the
dissolution medium contained
in a cylindrical vessel.
Collect sample periodically
and analyze for drug content.
Plot the amount of drug
against time.
http://www.youtube.com/watch?v=Eqz0X3y3vjs
18. Particle size, shape and surface
area
A particle is any unit of matter having
defined physical diameter.
Particle size should be controlled for
oral, parenteral and topical
formulations.
Bioavailability of a drug substance
depends on particle size
Flow properties for solid formulations
depends on particle size.
►Dissolution video
19. Particle size, shape and surface
area
Decrease in particle size,
increases the surface area.
Increased surface area,
increases solubility, dissolution
and bioavailability.
Particle shapes affect the flow,
surface area and packing
properties of a powder.
Intact Chopped
20. Crystal properties and
polymorphism
Polymorphism occurs
when a drug substance
exists in more than one
crystalline form with
different space lattice
arrangements.
Properties that may vary
due to polymorphisms are
Physical properties
(melting point)
Solubility
Rate of dissolution
21. Polymorphism affects bioavailability
and stability
A more soluble and fast-dissolving
polymorph is preferred over poorly
soluble and slowly dissolving form
Usually, only one polymorphic form is
thermodynamically stable at a given
temperature and pressure.
The less stable forms converts to the
stable form with time
Stable polymorph exhibits the highest
melting point, the lowest solubility, and
the maximum chemical stability.
23. Partition and distribution
coefficients
Measures drug's lipophilicity and determines
drug’s ability to cross cell membranes.
The ratio of concentration of a compound in the
two phases of a mixture of two immiscible
solvents at equilibrium
Po/w = (Coil/Cwater)equilibrium
The rate of drug transfer for passively absorbed
drugs is directly related to the lipophilicity of the
molecule.
24. Partition coefficient (LogP)
The ratio of concentrations of a unionized
compound between an aqueous and organic
solvent
You can measure the partition coefficient of
ionizable solutes by adjusting the pH so that
compound remains predominantly in the un-
ionized form in the solvent.
25. Distribution coefficient (LogD)
Log D is the ratio of the sum of the
concentrations of both ionized and
un-ionized form in octanol and
water
You can measure the distribution
coefficient by adjusting pH with a
buffer that will remain unaffected
due to incorporation of the
compound
26. Determination of partition
coefficients
Commonly determined using
an oil phase of octanol or
chloroform and water.
When P is greater than 1,
drug is classified as lipophilic,
when it is less than 1, drug is
hydrophilic
27. Permeation across a biological membrane
Drug permeability
The rate of drug transport
across a biological membrane
is called drug permeability.
Permeability provide
information regarding
absorption characteristics of
a drug.
You can use cell or isolated
organs for the permeability
study
Place drug in one side of the
membrane and stir the fluid
Collect samples periodically
and analyze for the drug
content.
Drug permeation
28. Let’s take the poll
Decrease in particle size , increases the surface
area and thus increase the drug absorption (T/F).
Dissolution is the rate limiting step for absorption
of highly soluble drug (T/F).
Drugs with a higher partition coefficient (Po/w>1) is
likely to be hydrophilic (T/F).
Two polymorphs of a drug may have different
solubility (T/F).
29. Drug stability
You have to investigate if a drug undergoes
degradation or loses its efficacy due to any
chemical or physical changes
Stability dictates what excipients to be used,
storage condition, packaging and shelf-life of a
drug.
Drug degradation may reduce the quantity of the
therapeutic agent in the dosage form.
Toxic products may form during the decomposition
process.
The physical appearance of the dosage may
change due to aging
30. Stability in the GI fluid
Drugs that degrade in the GIT is not
suitable for oral administration
Formulation should protect the drug from
degradation in the GIT
Orally unstable drugs are administered by
other routes of administration including
nasal, parenteral or pulmonary route.
31. Routes of drug degradation
Hydrolysis or solvolysis
Decomposes in the presence of solvents
Oxidation
React with atmospheric oxygen under the ambient
condition
Photolysis
Degrades in normal sunlight or room light
32. Routes of drug instability
Dehydration
Removal of water from the
molecule changes the
structure or physical
properties of the molecule.
Isomerization
Drugs convert into their
optical or geometrical
isomers. e.g. epinephrine
33. Hygroscopicity
Hygroscopic substances
Absorb moistures from the air
Deliquescent substances
Absorb moisture from the air to the extent that they
liquefy partially or wholly
Efflorescent substances
Substances become powdery and liberate their water of
crystallization
Drugs that possess any of these physical properties may
not be suitable for solid dosage forms.
34. Wettability
The tendency of a drug to get wet when it
comes in contact with the solvent
Influence the drug granulation process,
penetration of dissolution fluids into tablets
and granules, solubility and dispersibility
Sodium dodecyl sulfate (SDS) increases
wettability
35. Let’s take the poll
The presence of water causes solvolysis (T/F).
In dehydration, drugs absorb molecules of water
from the atmosphere (T/F).
Deliquescent substances become powdery by
releasing the water of crystallization (T/F).