Solubility is defined as the maximum amount of a substance that will dissolve in a given amount of solvent at a specified temperature. Solubility is a characteristic property of a specific solute–solvent combination, and different substances have greatly differing solubilities.
VIRUS PHARMACEUTICAL MICROBIOLOGY (BP303T)Unit-IIIPart-2Study of morphology, ...Ms. Pooja Bhandare
PHARMACEUTICAL MICROBIOLOGY (BP303T)Unit-IIIPart-2Study of morphology, classification, reproduction/replication and cultivation of Virus. Introduction, Def General characteristics of Viruses: small size characteristic shapes, obligate intracellular parasites no built-in metabolic machinery no ribosomes
only one type of nucleic acid
do not grow in size. Morphology of Virus: Helical, Polyhedral (Icosahedral) Viral Envelop, Complex virus, Classification of virus. Viral Replication LIFE CYCLE OF BACTIRIOPHAGES Lytic cycle: Attachment, Penetration, Biosynthesis, Maturation and Release of progeny Phage Particles. The Lysogenic Cycle, Cultivation of virus : Animal inoculation, Embryonated eggs or chick embryo method and Tissue culture or cell culture: Organ cultures Explant culture and Cell culture. Types of cell culture
1.Primary cell culture: 2. Diploid cell culture (Semi-continuous cell lines):3. Heteroploid cultures (Continuous cell lines):
MULTIPLICATION OF HUMAN VIRUS:1. Attachment of Viral Particles 2. Penetration 3. Uncoating 4. Replication Of Viral Nucleic Acids And Translation Of The Genome 5) Maturation Or Assembly Of Virions. ) 6. Release Of Virions Into The Surrounding Environment
Pharmaceutical Engineering Unit- 1 Chapter -1 Flow of fluid.pptxNikita Gupta
Here's a short way to understand the concept of pharmaceutical engineering . Take a look of this amazing ppt who describes the Chapter -1 of Pharmaceutical engineering i.e. Flow of Fluid.
In this presentation:
Surface Tension
Interfacial Tension
Definition of inerfacial tension in different ways
Measurement of interfacial and surface tesion
VIRUS PHARMACEUTICAL MICROBIOLOGY (BP303T)Unit-IIIPart-2Study of morphology, ...Ms. Pooja Bhandare
PHARMACEUTICAL MICROBIOLOGY (BP303T)Unit-IIIPart-2Study of morphology, classification, reproduction/replication and cultivation of Virus. Introduction, Def General characteristics of Viruses: small size characteristic shapes, obligate intracellular parasites no built-in metabolic machinery no ribosomes
only one type of nucleic acid
do not grow in size. Morphology of Virus: Helical, Polyhedral (Icosahedral) Viral Envelop, Complex virus, Classification of virus. Viral Replication LIFE CYCLE OF BACTIRIOPHAGES Lytic cycle: Attachment, Penetration, Biosynthesis, Maturation and Release of progeny Phage Particles. The Lysogenic Cycle, Cultivation of virus : Animal inoculation, Embryonated eggs or chick embryo method and Tissue culture or cell culture: Organ cultures Explant culture and Cell culture. Types of cell culture
1.Primary cell culture: 2. Diploid cell culture (Semi-continuous cell lines):3. Heteroploid cultures (Continuous cell lines):
MULTIPLICATION OF HUMAN VIRUS:1. Attachment of Viral Particles 2. Penetration 3. Uncoating 4. Replication Of Viral Nucleic Acids And Translation Of The Genome 5) Maturation Or Assembly Of Virions. ) 6. Release Of Virions Into The Surrounding Environment
Pharmaceutical Engineering Unit- 1 Chapter -1 Flow of fluid.pptxNikita Gupta
Here's a short way to understand the concept of pharmaceutical engineering . Take a look of this amazing ppt who describes the Chapter -1 of Pharmaceutical engineering i.e. Flow of Fluid.
In this presentation:
Surface Tension
Interfacial Tension
Definition of inerfacial tension in different ways
Measurement of interfacial and surface tesion
INCLUDES SPREADING COEFFICIENT AND ITS THEORY AND ALSO FEW OF ITS APPLICATION IN PHARMACEUTICAL FIELD
WILL BE HELPFUL FOR B PHARMACY STUDENTS
INCLUDES HOW IT IS DERIVED AND ALSO HOW IT IS RELATED TO SPREADING OF A CREAM OR OINTMENT ON OUR SKIN
IMPORTANCE OF SPREADING COEFFICIENT
POLYNUCLEAR HYDROCARBON : STRUCTURE AND USES OF NAPHTHELENE, ANTHRACENE,DI-PH...RishikaBehere1
Hello everyone, we the students of Gurunanak College of Pharmacy, Nagpur have created a presentation of subject pharmaceutical organic chemistry -2 of third semester, Unit 4 : polynuclear hydrocarbons . This presentation was made for the purpose of better understanding of the topic structure and medicinal uses of naphthelene , anthracene, diphenylmethane , triphenylmethane , phenanthrene and their derivatives . This portion covers topics like structure, properties , and medicinal uses of polynuclear hydrocarbons such as naphthelene , anthracene , di-phenylmethane, tri-phenylmethane , phenanthrene and their respective derivatives.
Unit 1- Effects of substituents on Mono substituted benzene RingAnjali Bhardwaj
Effects of substituents on reactivity and orientation of monosubstituted benzene compounds towards electrophilic substitution reaction
Activating & Deactivating group
Ortho and Para Directing group
Meta directing group
substitution on the benzene ring
Halides are Ortho & Para directing group why?
Solubility of liquids in liquids, The term miscibility refers to the mutual solubility of the component of liquid - liquid system, Raoult’s Law, Raoult’s law may be mathematically expressed as: Ideal solution, Real solution
4th (30.10.2014) on eutectic mixture by Diptarco SinghaDiptarco Singha
this ppt is very simple and has immence importance in physical pharmacy. it has been prepared based on the syllabus of WBUT & consists of informations of elimentary label...
INCLUDES SPREADING COEFFICIENT AND ITS THEORY AND ALSO FEW OF ITS APPLICATION IN PHARMACEUTICAL FIELD
WILL BE HELPFUL FOR B PHARMACY STUDENTS
INCLUDES HOW IT IS DERIVED AND ALSO HOW IT IS RELATED TO SPREADING OF A CREAM OR OINTMENT ON OUR SKIN
IMPORTANCE OF SPREADING COEFFICIENT
POLYNUCLEAR HYDROCARBON : STRUCTURE AND USES OF NAPHTHELENE, ANTHRACENE,DI-PH...RishikaBehere1
Hello everyone, we the students of Gurunanak College of Pharmacy, Nagpur have created a presentation of subject pharmaceutical organic chemistry -2 of third semester, Unit 4 : polynuclear hydrocarbons . This presentation was made for the purpose of better understanding of the topic structure and medicinal uses of naphthelene , anthracene, diphenylmethane , triphenylmethane , phenanthrene and their derivatives . This portion covers topics like structure, properties , and medicinal uses of polynuclear hydrocarbons such as naphthelene , anthracene , di-phenylmethane, tri-phenylmethane , phenanthrene and their respective derivatives.
Unit 1- Effects of substituents on Mono substituted benzene RingAnjali Bhardwaj
Effects of substituents on reactivity and orientation of monosubstituted benzene compounds towards electrophilic substitution reaction
Activating & Deactivating group
Ortho and Para Directing group
Meta directing group
substitution on the benzene ring
Halides are Ortho & Para directing group why?
Solubility of liquids in liquids, The term miscibility refers to the mutual solubility of the component of liquid - liquid system, Raoult’s Law, Raoult’s law may be mathematically expressed as: Ideal solution, Real solution
4th (30.10.2014) on eutectic mixture by Diptarco SinghaDiptarco Singha
this ppt is very simple and has immence importance in physical pharmacy. it has been prepared based on the syllabus of WBUT & consists of informations of elimentary label...
Solubility, Solubility Expressions, BCS Classification, Solute solvent interaction, Classification of solvents, Types of solutions, solubility of gases in liquids, liquids in liquid, Raoult's law, Ideal and Non-ideal solutions, association and solvation
Why is water solubility An important characteristic of a drug?
Solubility is the important parameter to achieve desired concentration of drugs in the systemic circulation that could exert desired physiological response. Any drug to be absorbed must be present in the form of an aqueous solution at the site of absorption.
Solubility & distribution phenomenon is useful for pharmacy student to understand the concept on solubility & distribution when study the physical pharmacy.
Pharmaceutical Solutions. Definition: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents.
Similar to solubility-150522124309-lva1-app6892.pdf (20)
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
Deep Leg Vein Thrombosis (DVT): Meaning, Causes, Symptoms, Treatment, and Mor...The Lifesciences Magazine
Deep Leg Vein Thrombosis occurs when a blood clot forms in one or more of the deep veins in the legs. These clots can impede blood flow, leading to severe complications.
Empowering ACOs: Leveraging Quality Management Tools for MIPS and BeyondHealth Catalyst
Join us as we delve into the crucial realm of quality reporting for MSSP (Medicare Shared Savings Program) Accountable Care Organizations (ACOs).
In this session, we will explore how a robust quality management solution can empower your organization to meet regulatory requirements and improve processes for MIPS reporting and internal quality programs. Learn how our MeasureAble application enables compliance and fosters continuous improvement.
Leading the Way in Nephrology: Dr. David Greene's Work with Stem Cells for Ki...Dr. David Greene Arizona
As we watch Dr. Greene's continued efforts and research in Arizona, it's clear that stem cell therapy holds a promising key to unlocking new doors in the treatment of kidney disease. With each study and trial, we step closer to a world where kidney disease is no longer a life sentence but a treatable condition, thanks to pioneers like Dr. David Greene.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
2. +
Objectives of the Chapter
After completion of this chapter, the student should be able to:
1. Understand the various types of pharmaceutical solutions.
2. Define solubility, saturated & unsaturated solutions and polar & non
polar solvents.
3. Understand the factors controlling the solubility of strong & weak
electrolytes.
4. Define partition coefficient & its importance in pharmaceutical
systems.
3. +
Importance of studying the
phenomenon of solubility
Understanding the phenomenon of solubility helps the pharmacist to:
1. Select the best solvent for a drug or a mixture of drugs.
2. Overcome problems arising during preparation of pharmaceutical
solutions.
3. Have information about the structure and intermolecular forces of the
drug.
4. Many drugs are formulated as solutions, or added as powder or solution
forms to liquids.
5. Drugs with low aqueous solubility often present problems related to their
formulation and bioavailability.
4. +
Definitions
Solution: is a mixture of two or more components that form a homogenous
mixture. The components are referred to the solute and/or solutes & the
solvent and/or solvents .
Solute: is the dissolved agent . (less abundant part of the solution )
Solvent : is the component in which the solute is dissolved (more abundant
part of the solution).
A saturated solution: is one in which an equilibrium is established between
dissolved and undissolved solute at a definite temperature. Or A solution that
contains the maximum amount of solute at a definite temperature
An unsaturated solution: or subsaturated solution is one containing the
dissolved solute in a concentration below that necessary for complete
saturation at a definite temperature.
5. +
Solubility
A supersaturated solution: contains more of the dissolved solute
than it would normally contain in a saturated state at a definite
temperature.
Solubility:
In a quantitative way: it is the concentration of solute in a saturated
solution at a certain temperature
In a qualitative way: it is the spontaneous interaction of two or more
substances (solute & solvent) to form a homogeneous molecular
dispersion
7. +
Solubility Curve
Any solution can be made saturated, unsaturated, or supersaturated
by changing the temperature.
8. +
Thermodynamic solubility of
drugs
The thermodynamic solubility of a drug in a solvent is the maximum
amount of the most stable crystalline form that remains in solution
in a given volume of the solvent at a given temperature and pressure
under equilibrium conditions.
The equilibrium involves a balance of the energy of three interactions
against each other:
(1) solvent with solvent
(2) solute with solute
(3) solvent and solute
9. +
Steps of solid going into solution.
1. Step 1: Hole open in the solvent
2. Step 2: One molecule of the solid breaks away from the bulk
3. Step 3: The solid molecule is enter into the hole in the solvent
10. +
Solubility process
A mechanistic perspective of solubilization process for organic solute
in water involves the following steps:
1. Break up of solute-solute intermolecular bonds
2. Break up of solvent-solvent intermolecular bonds
3. Formation of cavity in solvent phase large enough to
accommodate solute molecule
4. Transfer of solute into the cavity of solvent phase
5. Formation of solute-solvent intermolecular bonds
11. +
Tree types of interaction in the
solution process
1. solvent – solvent interaction
2. solute – solute interaction
3. solvent solute interaction
ΔH sol = ΔH 1 + ΔH 2 + ΔH 3
12. +
Enthalpy
The enthalpy change of solution refers to the overall amount of
heat which is released or absorbed during the dissolving
process (at constant pressure).
The enthalpy of solution can either be positive (endothermic
reaction) or negative (exothermic reaction).
The enthalpy of solution is commonly referred to as ΔH
solution.
13. +
Expression Symbol Definition
Molarity M, c Moles (gram molecular weights) of solute in 1 liter
(1000 ml) of solution.
Molality m Moles of solute in 1000 gm of solvent.
Normality N Gram equivalent weights of solute in 1 liter of
solution
Mole Fraction x Ration of moles of solute to total moles of solute+
solvent
Percentage by
Weight
% w/w gm of solute in 100 gm of solution
Percentage by
Volume
%v/v ml of solute in 100 ml of solution
Percentage
Weight in Volume
% w/v gm of solute in 100 ml of solution
Solubility
expressions
14. +
Solubility expressions
The USP lists the solubility of drugs as: the number of ml of solvent
in which 1g of solute will dissolve.
E.g. 1g of boric acid dissolves in 18 mL of water, and in 4 mL of
glycerin.
Substances whose solubility values are not known are described by
the following terms:
Term Parts of solvent required for 1
part of solute
Very soluble Less than 1 part
Freely soluble 1 to 10 parts
Soluble 10 to 30 parts
Sparingly soluble 30 to 100 parts
Slightly soluble 100 to 1000 parts
Very slightly soluble 1000 to 10 000 parts
Practically insoluble More than 10 000 parts
16. +
Solubility expressions: BCS
High solubility
The highest single unit dose is completely soluble in 250 ml or
less of aqueous solution at pH 1 - 6.8 (37 °C)
Xanax (alprazolam)
anxiety disorder
17. +
Solvent - Solute Interactions
In pre - or early formulation, selection of the most suitable solvent is
based on the principle of
“like dissolves like”
That is, a solute dissolves best in a solvent with similar chemical
properties. Or two substances with similar intermolecular forces are
likely to be soluble in each others
Polar solutes dissolve in polar solvents. E.g salts & sugar dissolve in
water .
Non polar solutes dissolve in non polar solvents. Eg. naphtalene
dissolves in benzene.
18. +
POLAR SOLUTE - POLAR
SOLVENT
Ammonia Dissolves in Water:
Polar ammonia molecules dissolve in polar water molecules.
These molecules mix readily because both types of molecules
engage in hydrogen bonding.
Since the intermolecular attractions are roughly equal, the
molecules can break away from each other and form new
solute (NH3), solvent (H2O) hydrogen bonds.
19. +
Alcohol Dissolves in Water:
The -OH group on alcohol is polar and mixes with the polar
water through the formation of hydrogen bonds.
A wide variety of solutions are in this category such as sugar in
water, alcohol in water, acetic and hydrochloric acids.
20. +
Solute-Solvent interactions
If the solvent is A & the solute is B, and the forces of attraction are represented by
A-A, B-B and A-B,
One of the following conditions will occur:
1. If A-A >> A-B The solvent molecules will be attracted to each other
& the solute will be excluded. Example: Benzene & water, where benzene
molecules are unable to penetrate the closely bound water aggregates.
2. If B-B >> A-A The solvent will not be able to break the binding forces
between solute molecules. Example NaCl in benzene, where the NaCl crystal is
held by strong electrovalent forces which cannot be broken by benzene.
3. If A-B >> A-A or B-B, or the three forces are equal The solute will . form
a solution. Example: NaCl in water.
21. +
Classification of solvents & their
mechanism of action
1. Polar solvents
2. Non polar solvents
3. Semi polar solvents
22. +
Polar solvents
The solubility of a drug is due in large measure to the polarity of the solvent,
that is, to its dipole moment. Polar solvents dissolve ionic solutes and other
polar substances.
The ability of the solute to form hydrogen bonds is a far more significant
factor than is the polarity as reflected in a high dipole moment
Water dissolves phenols, alcohols and other oxygen & nitrogen containing
compounds that can form hydrogen bonds with water.
23. +
The solubility of a substance also depends on structural features such
as the ratio of the polar to the nonpolar groups of the molecule.
As the length of a nonpolar chain of an aliphatic alcohol increases, the
solubility of the compound in water decreases
Straight-chain monohydroxy alcohols, aldehydes, ketones, and acids
with more than four or five carbons cannot enter into the hydrogen-
bonded structure of water and hence are only slightly soluble.
Polar solvents
24. +
When additional polar groups are present in the molecule, as found
in propylene glycol, glycerin, and tartaric acid, water solubility
increases greatly.
Branching of the carbon chain reduces the nonpolar effect and leads to increased water
solubility.
Tertiary butyl alcohol is miscible in all proportions with water, whereas n-butyl alcohol
dissolves to the extent of about 8 g/100 mL of water at 20°C.
tert-Butanol n-Butanol
Polar solvents
25. +
Hydrogen bonding is the attractive
interaction of a hydrogen atom with an
electronegative atom, such as nitrogen,
oxygen
Dipole-dipole forces are electrostatic interactions of
permanent dipoles in molecules.
26. +
Non polar solvents
Non-polar solvents are unable to reduce the attraction between the
ions of strong and weak electrolytes because of the solvents' low
dielectric constants.
They are unable to form hydrogen bonds with non electrolytes.
Non polar solvents can dissolve non polar solutes through weak van der
Waals forces
Example: solutions of oils & fats in carbon tetrachloride or benzene.
Polyethylene glycol 400
Castor oil
27. +
Semi polar solvents
Semi polar solvents, such as ketones can induce a certain degree of
polarity in non polar solvent molecules. For example, benzene, which
is readily polarizable, becomes soluble in alcohol
They can act as intermediate solvents to bring about miscibility of
polar & non polar liquids.
Example: acetone increases solubility of ether in water.
Propylene glycol has been shown to increase the mutual solubility of
water and peppermint oil and of water and benzyl benzoate
30. +
Polarity
The solubility of the drug substance is attributable in large part to the
polarity of the solvent, often expressed in terms of dipole moment,
related to the dielectric constant.
Solvents with high dielectric constants dissolve ionic compounds
(polar drugs) readily because of ion–dipole interactions,
Solvents with low dielectric constants dissolve hydrophobic
substances (non-polar drugs)
polar solvents, with examples such as water and glycerin;
non-polar solvents, with example such as oils.
Solvents with intermediate dielectric constants are classified as
semipolar.
31. + Types of solutions
Solutions of pharmaceutical importance include:
Gases in liquids
Liquids in liquids
Solids in liquids
32. +
When the pressure above the
solution is released (decreases),
the solubility of the gas
decreases
As the temperature increases the
solubility of gases decreases
Solubility of gases in liquids
33. +Solubility of liquids in liquids
Preparation of pharmaceutical solutions involves mixing of 2 or more liquids
Alcohol & water to form hydroalcoholic solutions
volatile oils & water to form aromatic waters
volatile oils & alcohols to form spirits , elixirs
Liquid-liquid systems may be divided into 2 categories:
1. Systems showing complete miscibility such as alcohol & water, glycerin & alcohol,
benzene & carbon tetrachloride.
2. Systems showing Partial miscibility as phenol and water; two liquid layers are
formed each containing some of the other liquid in the dissolved state.
The term miscibility refers to the mutual solubility of the components in liquid-liquid
systems.
34. +
Solubility of liquids in liquids
Complete miscibility occurs when: The adhesive forces between
different molecules (A-B) >> cohesive forces between like molecules
(A-A or B-B).
Polar and semipolar solvents, such as water and alcohol, glycerin
and alcohol, and alcohol and acetone, are said to be completely
miscible because they mix in all proportions.
Nonpolar solvents such as benzene and carbon tetrachloride are
also completely miscible.
35. +
Solubility of liquids in liquids
Partial miscibility results when: Cohesive forces of the constituents of a mixture
are quite different, e.g. water (A) and hexane (B). A-A » B-B.
When certain amounts of water and ether or water and phenol are mixed, two
liquid layers are formed, each containing some of the other liquid in the
dissolved state.
The effect of temperature on the miscibility of two-component liquids is
expressed by phase diagrams.
In the phase diagrams of two-component liquids, the mixture will have an upper
critical solution temperature, a lower critical solution temperature or both.
39. + Solubility of solids in liquids
Factors influencing solubility
1- Particle size (surface area) of drug particles
↓Particle size → ↑ surface area→ ↑Solubility
40. +
o So is the solubility of large particles
o S is the solubility of fine particles
o γ is the surface tension of the particles
o V is molar volume
o T is the absolute temperature
o r is the radius of the fine particle
o R is the gas constant
Solubility of solids in liquids
Factors influencing solubility
41. +
Example
A solid is to be comminuted so as to increase its solubility by 10%,
that is s/so is to become 1.10
What must be the final particle size, assuming that the surface
tension of the solid is 100 dynes/cm and the volume per mile is 50
cm3? The temperature is 27oC
Answer: 0.042µm
42. +
2- Molecular size
Molecular size will affect the solubility.
The larger the molecule or the higher its molecular weight the less
soluble the substance.
Larger molecules are more difficult to surround with solvent
molecules in order to solvate the substance.
In the case of organic compounds the amount of carbon branching
will increase the solubility since more branching will reduce the size
(or volume) of the molecule and make it easier to solvate the
molecules with solvent
Solubility of solids in liquids
Factors influencing solubility
43. +
3- The boiling point of liquids and the melting point of solids:
Both reflect the strengths of interactions between the molecules in
the pure liquid or the solid state.
In general, aqueous solubility decreases with increasing boiling
point and melting point.
Solubility of solids in liquids
Factors influencing solubility
44. +
4-The influence of substituents on the solubility of molecules
in water can be due to their effect on the properties of the solid
or liquid (for example, on its molecular cohesion, or to the
effect of the substituent on its interaction with water molecules.
Substituents can be classified as either hydrophobic or
hydrophilic, depending on their polarity
Solubility of solids in liquids
Factors influencing solubility
45. +
Polar groups such as –OH capable of hydrogen
bonding with water molecules impart high
solubility
Non-polar groups such as –CH3 and –Cl are
hydrophobic and impart low solubility.
Ionization of the substituent increases
solubility, e.g. –COOH and –NH2 are slightly
hydrophilic whereas –COO– and –NH3 are very
hydrophilic.
Influence of substituents on the
solubility
46. +
The position of the substituent on the molecule can influence its effect on
solubility, for example the aqueous solubilities of o-, m- and p-
dihydroxybenzenes
Influence of substituents on the
solubility
47. +
5-Temperature
Temperature will affect solubility. If the solution process absorbs energy
then the solubility will be increased as the temperature is increased.
If the solution process releases energy then the solubility will decrease
with increasing temperature.
Generally, an increase in the temperature of the solution increases the
solubility of a solid solute.
A few solid solutes are less soluble in warm solutions.
For all gases, solubility decreases as the temperature of the solution
increases.
Solubility of solids in liquids
Factors influencing solubility
48. +
6-Crystal properties
Polymorphic Crystals, Solvates, Amorphous forms
Solubility of solids in liquids
Factors influencing solubility
Polymorphs have the same chemical structure but different physical properties,
such as solubility, density, hardness, and compression characteristics
A drug that exists as an amorphous form (non crystalline form) generally
dissolves more rapidly than the same drug in crystalline form
49. +
7- PH
is one of the primary influences on the solubility of most drugs that contain
ionizable groups
Large number of drugs are weak acids or weak base.
Solubility depends on the degree of ionization.
Degree of ionization depends on the pH
Solubility of solids in liquids
Factors influencing solubility
About 85% of marketed drugs contain functional groups that are ionised
to some extent at physiological pH (pH 1.5 – 8).
50. +
carboxyl group (RCO2H)
Carboxylic acids containing
more than five carbons are
relatively insoluble in water,
they react with dilute sodium
hydroxide, carbonates and
bicarbonates to form soluble
salts.
As the number of carbons in a
carboxylic acid series becomes
greater, the boiling point
increases and the solubility in
water decreases.
51. +
Carboxylic acids with 12 to 20 carbon atoms are often referred to as fatty
acids
Fatty acids containing more than 10 carbon atoms form soluble soaps with
the alkali metals. They are soluble in solvents having low dielectric
constants; for example, oleic acid (C17H33COOH) is insoluble in water but is
soluble in alcohol and in ether.
Benzoic acid is soluble in sodium hydroxide solution
Phenol is weakly acidic and only slightly soluble in water but quite
solution in dilute NaOH solution.
Organic compounds containing a basic nitrogen atom
Most of these weak electrolytes are not very soluble in water but are
soluble in dilute solutions of acids
52. +
]
[
]
][
[ 3
HP
P
O
H
Ka
)
]
[
]
[
log(
]
log[
log 3
HP
P
O
H
Ka
)
]
[
]
[
log(
log
]
log[ 3
HP
P
K
O
H a
S The total solubility of drug ( un-ionized + ionized) ]
[
]
[
P
HP
S
solubility of the un-ionized form of drug in solution ]
[HP
S
S
S
S
S
pK
pH a
p
log
P
O
H
O
H
HP 3
2
53. + The equation relating the solubility, S, of an acidic
drug to the pH of the solution is:
S
S
S
pK
pH a
log
S The total solubility of the drug (un-ionized + ionized)
The solubility of the un-ionized form of the drug
S
Acidic drugs
pH is the pH below which the drug separates from solution as the undissociated
acid.
From equation we can calculate:
If the pH of the solution is known then we can calculate the solubility of an acidic drug at
that pH.
minimum pH that must be maintained in order" to prevent precipitation from a solution
of known concentration.
Henderson-Hasselbalch
55. +The equation relating the solubility, S,
of an basic drug to the pH of the solution is:
S
S
S
pK
pH a
log
S The total solubility of the drug (un-ionized + ionized)
The solubility of the un-ionized form of the drug
S
Basic drugs
a
pK
From equation we can calculate:
If the pH of the solution is known then we can calculate the solubility of an basic drug at
that pH.
minimum pH that must be maintained in order" to prevent precipitation from a solution
of known concentration.
The pH is the pH above which the drug begins to precipitate from solution as the
free base
Henderson-Hasselbalch
56. +
Ionization of drugs
For acidic drug
pH = pKa + log [ionized drug]
[un-ionized drug]
For basic drug
pH = pKa + log [un-ionized drug]
[ionized drug]
P
O
H
O
H
HP 3
2
)
]
[
]
[
log(
HP
P
pK
pH a
OH
BH
O
H
B 2
)
]
[
]
[
log(
BH
B
pK
pH a
S
S
S
pK
pH a
log
S
S
S
pK
pH a
log
]
[
]
[
P
HP
S
]
[HP
S
]
[
]
[
BH
B
S
]
[B
S
59. + Calculate the pHp of a 1% sodium phenobarbital solution.
From Merck Index:
(i.e. 1% phenobarbital will precipitate at or below a pH of 8.3)
S
S
S
pK
pH a
p
log
60. +
What is the pH below which sulfadiazine (pKa = 6.48) will begin to
precipitate in an infusion fluid, when the initial molar
concentration of sulfadiazine sodium is 4X 10 -2 mol/ dm 3 and
the solubility of sulfadiazine is 3.07X 10 -4 mol/ dm 3 ?
The pH below which the drug will precipitate is calculated using equation
S
S
S
pK
pH a
log
Example
61. +
Example
Example:
If 8.66 mg/ml procaine solution stable (i.e., no ppt.) at pH 7.4 given that 1
gm dissolves in 200 ml water and pka = 8.05.
S
S
S
pK
pH a
log
S
S = 8.66 mg/ml
pka = 8.05
= 1gm/ 200ml = 1000mg/200 ml =5 mg/ ml
pH = 8.05 + log (5/ 8.66 – 5)
pH = 8.05 + log 1.37
pH = 8.19
This is maximum pH and 7.4 is less than 8.19, therefore solution is
stable and no ppt. occurs.
62. +
Ionization and pH
Strong vs. weak acids and bases
1. Strong – ionized at all pHs
2. Weak – only ionized at certain pHs (most drugs are weak acids or weak
bases
3. Ionized drugs are not very lipid soluble- only nonionized form of drug
crosses membrane readily
4. Percent ionization is pH dependent
5. pKa is the negative log of the ionization constant and is
equal to the pH at which a drug is 50% ionized
6. Weak acids become highly ionized as pH increases
7. Weak bases become highly ionized as pH decreases
63. +
Computing Ionization Ratios
According to the Henderson-Hasselbalch equation, the
difference between the pH of the solution and the pKa of the
drug is the common logarithm of the ratio of ionized to
unionized forms of the drug.
For acid drugs
log(ionized/unionized) = pH - pKa, or
ratio of ionized to unionized is 10X / 1, where
X = pH – pKa
)
]
[
]
[
log(
HP
P
pK
pH a
64. +
Computing ionization ratios
For basic drugs, everything is the same except that the ratio reverses:
Log(unionized/ionized) = pH – pKa, or
Ratio of unionized to ionized is 10X / 1, where
X = pH – pKa
)
]
[
]
[
log(
HP
P
pK
pH a
)
]
[
]
[
log(
BH
B
pK
pH a
66. +
Lipoid diffusion- weak acids and weak bases
Henderson-Hasselbalch equation
Determines extent of ionization
pKa = pH at which 50% of drug is ionized.
WEAK ACIDS:
log (ionized form/nonionized form)= pH – pKa
WEAK BASES:
log (nonionized form/ionized form)= pH – pKa
)
]
[
]
[
log(
HP
P
pK
pH a
)
]
[
]
[
log(
BH
B
pK
pH a
67. + PASSIVE DIFFUSION
•water soluble drug
(ionized or polar) is
readily absorbed via
aqueous channels or
pores in cell
membrane.
•Lipid soluble drug
(nonionized or non
polar) is readily
absorbed via cell
membrane itself.
68. +
Examples
P weak acid, has a pKa of 5.5. Taken orally, it is in a
stomach solution of pH 3.5.
pH – pKa = 3.5 – 5.5 = -2
Since it is an acid drug, we use the alphabetical
formula ionized/unionized.
ionized/unionized = 10-2/1= 1/100
For every 1 molecule of P that is ionized, 100 are
unionized. P in the stomach is highly fat soluble.
69. +
But look what happens…
The highly fat soluble P readily crosses the stomach
membranes and enters blood plasma, which has a
pH of 7.5
pH – pKa = 7.5 – 5.5 = 2
ionized/unionized = 102/1= 100/1
For every 100 molecules of P that are ionized, only 1 is
unionized. P in the blood is not very fat soluble.
P will be subject to ion trapping.
71. + Percent Ionization of Aspirin [Stomach]
pKa of Aspirin [weak acid] = 3.4 (50% HA and A- at pH 3.4)
pH stomach = 1.4 pH blood = 7.4
pH = pKa + log (A-)/(HA) [ H-H equation]
pH - pKa = log (A-)/(HA)
1.4 – 3.4 = - 2 log of 0.01= -2 (stomach)
A- / HA= 0.01/ 1 so HA is 100 fold greater than A
HA moves from the stomach into the blood (good absorption)
Percent Ionization of Aspirin [Blood]
Stomach (pH=1.4) Blood (pH=7.4)
pH - pKa = log (A-)/(HA)
7.4 – 3.4 = 4 log of 10,000 = 4 (blood)
A- / HA= 10,000/ 1
so A- is 10,000 fold greater than HA
72. +
Another example
M, a weak base with a pKa of 7.5 is dissolved in the stomach, pH 3.5
pH – pKa = 3.5 – 7.5 = -4
Since M is a base drug, we use the ratio backwards: unionized/ionized.
unionized/ionized = 10-4/1= 1/10,000
In the stomach, M will be mostly ionized, and not very fat soluble.
73. +
But…
If we inject M intravenously into the blood, with a pH of 7.5,
pH – pKa = 7.5 – 7.5 = 0
unionized/ionized = 100 = 1/1
In the blood, M will be equally ionized and unionized.
74. +
Percent Ionization of Codeine
[Stomach]
• CODEINE (weak base) pKa = 7.9
• Stomach pH=1.9 Blood pH =7.4
pH - pKa = log(B)/(BH+) [H-H equation]
1.9 - 7.9 = -6 log 0.0000001 = -6 [Stomach]
B/ BH+ = 0.000001/1 so BH+ is 1,000,000 fold greater than B.
Little B (codeine) is absorbed into the blood (poor absorption)
75. +
An oddity
Caffeine is a base drug, but it has a pKa of 0.5
pH – pKa = 3.5 – 0.5 = 3
Since caffeine is a base drug, we use the ratio backwards:
unionized/ionized.
unionized/ionized = 103/1= 1000/1
In the stomach, caffeine will be mostly unionized, and fat
soluble!
In the blood, caffeine will be even more unionized and fat
soluble:
pH – pKa = 7.5 – 0.5 = 7, ratio = 107/1= 10,000,000/1.
76. +
WEAK ACIDS
log (ionized form/nonionized form)= pH – pKa
A drug is a weak acid.
pKa is 3.5.
If stomach pH is 1.5, what percentage of drug will be in absorbable form?
pH – pKa = 1.5 – 3.5 = - 2
pH = pKa + log [ionized drug] / [un-ionized drug]
(pH) – (pKa) -2 -1 0 1 2
Weak acid
% nonionized
99 90 50 10 1
77. +
Remember – absorbable means
nonionized !
pH – pka = -2
This (-2) in the table for weak acid matches to 99%.
And this is supposed to be the nonionized form, which is same
as “absorbable form” that is asked in this problem.
Hence the absorbable form is 99%.
78. +
Weak bases
log (nonionized form/ionized form)= (pH) – (pKa)
A drug is a weak base.
pKa is 8.
At pH 6, what percentage of drug will be in the ionized form?
pH – pKa = 6 – 8 = - 2
(pH) – (pKa) -2 -1 0 1 2
Weak base
% nonionized
1 10 50 90 99
79. +
Please remember – ionized means
nonabsorbable !
pH – pka has come as -2.
In the table for weak base, -2 matches with 1%. But this 1% is
nonionized form. What is asked is – ionized.
So, ionized is 100 – 1 = 99%.
80. +
Co-solvent effect on solubility
The presence of a co-solvent can increase the
solubility of hydrophobic organic chemicals
Co-solvents can completely change the solvation
properties of “water”
The nonelectrolytes and the undissociated molecules of
weak electrolytes more soluble in a mixture of solvents than
in one solvent alone. This phenomenon is known as
cosolvency, and the solvents that, in combination, increase
the solubility of the solute are called cosolvents.
81. +
Fig. 9-5. The influence of
alcohol concentration on
the dissociation constant of
phenobarbital.
82. +
States that a solute will distribute itself between two immiscible
solvents so that the ratio of its concentration in each solvent is
equal to the ratio of its solubility in each one
CO
Kd = ---------
CW
Co= molar conc in organic layer
Cw= molar conc in aqueous layer
Kd= distribution constant, distribution ratio, distribution
coefficient, or partition coefficient
Distribution of Solutes between Immiscible
Solvents
83. 1-Octanol is the most frequently used lipid phase in pharmaceutical research.
This is because:
It has a polar and non polar region (like a membrane phospholipid)
Po/w is fairly easy to measure
Po/w often correlates well with many biological properties
Xaqueous Xoctanol
P
Partition coefficient P (usually expressed as log10P or logP) is defined as:
P =
[X]octanol
[X]aqueous
P is a measure of the relative affinity of a molecule for the lipid and aqueous phases in
the absence of ionisation.
Partition coefficients
85. +
Application
Extraction
it is used to determine the efficiency with which one
solvent can extract a compound from a second solvent
extract natural drugs from a solvent with several
portions of an immiscible solvent
86. +
Application
Preservative action
the concentration of preservative to be used in an emulsion can be
calculated from the distribution law to give the effective antimicrobial
concentration in the water phase
87. +
Drug Absorption/Distribution/Action
Hydrophobic drugs (high partition coefficients) are preferentially
distributed to hydrophobic compartments such as lipid bilayers of
cells
Hydrophilic drugs (low partition coefficients) preferentially are found
in hydrophilic compartments such as blood serum.
88. +
If only the undissociated form is present at low pH then we need to find S0.
What is the solubility of benzylpenicillin G at a pH
sufficiently low to allow only the nondissociated form of
the drug to be present?
The pKa of benzylpenicillin G is 2.76 and the solubility of
the drug at pH 8.0 is 0.174 mol/ dm 3
(From R. E. Notari, Biopharmaceutics and Pharmacokinetics, 2nd edn, Marcel Dekker, New York, 1978.)
S
S
S
pK
pH a
log
24
.
5
174
.
0
log
76
.
2
0
.
8
S
S
3
6
0 /
10
1 dm
mol
S
Example
89. +
In general
solubility increases exponentially as cosolvent fraction increases.
need 5-10 volume % of cosolvent to see an effect.
extent of solubility enhancement depends on type of cosolvent
and solute
effect is greatest for large, nonpolar solutes
more “organic” cosolvents have greater effect
propanol>ethanol>methanol