Polymorphism is very important in those areas of chemical research where full
characterization of a material has a pivotal role in determining its ultimate use, e.g., in
pharmaceutical, pigment, agrochemical, explosive, and fine chemical industries.
Polymorphism has been recognized as an important element of drug development
Polymorphic forms of a drug substance can have different chemical and physical
properties, including melting point, chemical reactivity, apparent solubility, apparent
solubility, dissolution rate, optical, electrical, and mechanical properties, vapor pressure,
stability, and density.
These properties can have a direct effect on the ability to process and/or manufacture the
drug substance and the drug product, as well as on drug product stability, dissolution, and
bioavailability.
Polymorphism is very common among pharmaceutical substances and thermodynamic
stability of a polymorph can impact pharmaceutical properties such as bioavailability,
processability and manufacturability.
Polymorphic forms possess higher potential energy with respect to the
thermodynamically stable or lowest entry forms.
Different polymorphic phase’s exhibit unique physicochemical properties include
solubility, dissolution rates which can influence bioavailability.
The ability to isolate, differentiate, and characterize individual polymorphs is a major
challenge to the pharmaceutical industry.
PHARMACEUTICAL APPLICATIONS OF POLYMORPHISM
- Improved physical stability
- Ease of handling
- Improved bioavailability
- Better chemical stability
- Sustained release
Polymorphism is the ability of solid materials to exist in two or more crystalline forms with different arrangements or conformations of the constituents in the crystal lattice. ... More than 50% of active pharmaceutical ingredients (APIs) are estimated to have more than one polymorphic form
Powder Technology
Particle analysis in pharmaceuticals
Determination of particle size and surface area
Large scale equipment for powders
Types of powders
Accelerated stability studies, Arrhenius equation, steps involved in prediction of shelf life, climatic zones as per the ICH guidelines, limitations of Accelerated stability study
Polymorphism is the ability of solid materials to exist in two or more crystalline forms with different arrangements or conformations of the constituents in the crystal lattice. ... More than 50% of active pharmaceutical ingredients (APIs) are estimated to have more than one polymorphic form
Powder Technology
Particle analysis in pharmaceuticals
Determination of particle size and surface area
Large scale equipment for powders
Types of powders
Accelerated stability studies, Arrhenius equation, steps involved in prediction of shelf life, climatic zones as per the ICH guidelines, limitations of Accelerated stability study
The chapter deals with the preformulation studies that have to be considered while designing a dosage form and developing a formulation that is suitable for a patient. Here, physical and chemical properties of a drug substance are studied along with biopharmaceutical classification of drugs. Also a detailed study on the application of preformulation studies in different dosage forms are also studied.
State of matter and properties of matter (Part-7)(Solid-crystalline, Amorpho...Ms. Pooja Bhandare
CRYSTALLINE SOLID, Types of Crystalline solid, AMORPHOUS SOLID, Difference between crystalline solid and amorphous solid, Why does the amorphous form of drug have better bioavaibility that crystalline couterpaerts?, Polymorphism,
TYPES OF POLYMORPHISM, PROPERTY OF POLYMORPHS, Methods of preparation of Polymorphs, Methods to determine Polymorphism Characterization of Polymorphs, Pharmaceutical Application
Solid State of matter,
Crystalline, Amorphous & Polymorphism Forms,
Classification of solid state of matter On the basis of Internal Structure,
PHYSICAL PHARMACEUTICS-I,
Habet,
B.Pharm,
SUBJECT:-Pharmaceutical engineering 1
CONTENTS
-general study of composition
-properties
factors affecting the selection of material of pharmaceutical plant
-construction with special reference to S.S and glass
Decomposition and stabilization of pharmaceutical productsArshad Khan
Drug stability:Stabilization of medicinal agents against common reactions like hydrolysis & oxidation. Accelerated stability testing in expiration dating of pharmaceutical dosage forms. Photolytic degradation and its prevention.
Preformulation Studies: Introduction to preformulation, goals and objectives, study of
physicochemical characteristics of drug substances.
a. Physical properties: Physical form (crystal & amorphous), particle size, shape, flow
properties, solubility profile (pKa, pH, partition coefficient), polymorphism.
b. Chemical Properties: Hydrolysis, oxidation, reduction, racemisation, polymerization
BCS classification of drugs & its significant
Application of preformulation considerations in the development of solid, liquid oral and
parenteral dosage forms and its impact on stability of dosage forms.
In this slide, you will learn about what is polymorphism, types, and properties of polymorphism, the application of polymorphism in pharmaceutical industries, polymorphism of several drugs. Hope you will like it.
The chapter deals with the preformulation studies that have to be considered while designing a dosage form and developing a formulation that is suitable for a patient. Here, physical and chemical properties of a drug substance are studied along with biopharmaceutical classification of drugs. Also a detailed study on the application of preformulation studies in different dosage forms are also studied.
State of matter and properties of matter (Part-7)(Solid-crystalline, Amorpho...Ms. Pooja Bhandare
CRYSTALLINE SOLID, Types of Crystalline solid, AMORPHOUS SOLID, Difference between crystalline solid and amorphous solid, Why does the amorphous form of drug have better bioavaibility that crystalline couterpaerts?, Polymorphism,
TYPES OF POLYMORPHISM, PROPERTY OF POLYMORPHS, Methods of preparation of Polymorphs, Methods to determine Polymorphism Characterization of Polymorphs, Pharmaceutical Application
Solid State of matter,
Crystalline, Amorphous & Polymorphism Forms,
Classification of solid state of matter On the basis of Internal Structure,
PHYSICAL PHARMACEUTICS-I,
Habet,
B.Pharm,
SUBJECT:-Pharmaceutical engineering 1
CONTENTS
-general study of composition
-properties
factors affecting the selection of material of pharmaceutical plant
-construction with special reference to S.S and glass
Decomposition and stabilization of pharmaceutical productsArshad Khan
Drug stability:Stabilization of medicinal agents against common reactions like hydrolysis & oxidation. Accelerated stability testing in expiration dating of pharmaceutical dosage forms. Photolytic degradation and its prevention.
Preformulation Studies: Introduction to preformulation, goals and objectives, study of
physicochemical characteristics of drug substances.
a. Physical properties: Physical form (crystal & amorphous), particle size, shape, flow
properties, solubility profile (pKa, pH, partition coefficient), polymorphism.
b. Chemical Properties: Hydrolysis, oxidation, reduction, racemisation, polymerization
BCS classification of drugs & its significant
Application of preformulation considerations in the development of solid, liquid oral and
parenteral dosage forms and its impact on stability of dosage forms.
In this slide, you will learn about what is polymorphism, types, and properties of polymorphism, the application of polymorphism in pharmaceutical industries, polymorphism of several drugs. Hope you will like it.
Evaluation of Various Polymorphs by Different Techniques and Their Characteri...theijes
Polymorphism evolved out as a major point of attention for industry as well as regulatory agencies. Many pharmaceutical compounds exist in different crystalline forms and thus exhibit polymorphism. Polymorphism may affect Chemical and Physical Stability, Apparent Solubility, Dissolution, Bioavailability and Bioequivalence and Manufacturability of drug product, which require special attention during product development as it affects the quality, safety and efficacy of drug product. In addition to this, impact of polymorphism, monitoring and control of polymorphism and reporting scheme of polymorphic information in Abbreviated New Drug Application.
A drug injected intravascularly directly enters the systemic circulation and exerts its pharmacological effects.
Majority of drugs administered extravascularly, generally orally.
If intended to act systemically, such drugs can exert their pharmacological actions only when they come into blood circulation from their site of application. So, absorption is an important step.
- 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
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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
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
3. Path for Presentation
➢ Introduction
➢ Need to study polymorphism (rational for selecting polymorph)
➢ Structural aspects of polymorphs
➢ Properties of polymorphs
➢ Types of polymorphism
➢ Methods of preparation of polymorph
➢ Characterization of polymorphism
➢ Pharmaceutical applications of polymorphism
➢ Regulatory considerations
➢ Polymorphism of several drugs
➢ Conclusion
➢ References
19/10/2022 3
4. Introduction
• When a substance exists in more than one crystalline form, the different form
are designated as polymorphs and the phenomenon as polymorphism.
e.g.:-
• Carbon: diamond in a cubic ( tetrahedral lattice arrangement)
• Graphite in sheet of a hexagonal lattice.
• Differences in the internal structures of polymorphs result in their distinct
physical and chemical properties.
• More than 50% of APIs are estimated to have more than one polymorphic form.
• The best known polymorphs showing a significantly different bioavailability are
Chloramphenicol palmitate and Mefenamic acid.
19/10/2022 4
6. 19/10/2022 6
Need to study polymorphism
• Depending upon their relative stability, one of the several polymorphic form will
be physically more stable than others.
• Stable polymorph represents the lowest energy state, has highest melting
point and least aqueous solubility.
• Metastable form represent the higher energy state, have lower melting point
and high aqueous solubility.
• Metastable form converted to the stable form due to their higher energy state.
• Metastable form shows better bioavailability and therefore preferred in
formulations.
• Only 10% of the pharmaceuticals are present in their metastableform.
• The example is chloramphenicol palmitate.
Other like novobiocin , griseofulvine , Carbamazepine , aspirin and ampicilline .
7. Structural aspects of polymorph
• Configurational polymorph
occurs with molecules that have
a relatively rigid conformation.
Such polymorphs have different
3D structures.
• e.g.:- Carbamazepine
Configurational
polymorph
• Conformational polymorph
occurs with drug molecules that
have flexible structures and the
molecule can take various
conformations.
• e.g.:- Ritonavir
Conformational
polymorph
19/10/2022 7
9. Types of polymorphism
• When the change of one
polymorphic form to other at the
transition temperature is reversible,
the phenomenon called
Enantiotropy and the polymorphic
forms are called enantiotropes.
• e.g.:- Sulphur, Carbamazepine
Enantiotropy
• Monotropy occurs when one form
is stable and the other metastable.
The metastable changes to the
stable form at all temperature and
the change is not reversible.
• e.g.:- Chloramphenicol palmitate,
Metolazone
Monotropy
19/10/2022 9
12. Pharmaceutical applications
Preparation of physically
stable dosage form
Influence on solubility,
dissolution and
bioavailability
Influence on drug
product
manufacturability
Influence on
stability
Effect on tableting
Miscellaneous
application
19/10/2022 12
13. Regulatory considerations
• Due to difference in the physicochemical properties of
polymorphs, in ANDAs, careful attention is paid to the effect
of polymorphism in the context of generic drug product
equivalency.
• Three decision trees for solid oral dosage forms or liquid
suspensions are provided for evaluating when and how
polymorphs of drug substances should be monitored and
controlled in ANDAsubmission.
• For approval of a new drug, US-FDA states that appropriate
analytical procedures need to be used to detect polymorphs,
hydrates, amorphous forms of the drug substance.
19/10/2022 13
14. Commercial product based on
polymorphism
(ref: Hungarian Intellectual Property Office)
Brand name API Patentee
Allegra Fexofenadin Sanofi
Cozaar Losartan Merck
Clarinex Desloratadine Schering-Plough
Epivir Lamivudine GSK
Geodon Ziprasidone Pfizer
Omnicef Cefdinir Abbott
19/10/2022 14
15. Polymorphism in several drugs
Drug Polymorphism
aspects
Bioavailability issues
Chloramphenicol
palmitate
Exist in 3 polymorphic
forms (A,B,C).
Stable form- A,
metastable form- B,
unstable form- C
Form B dissolves faster than
form A, and has a much higher
solubility. Low serum levels for
the stable polymorph A were
observed.
Carbamazepine 4 anhydrous polymorphs Recent study reveals that
the were characterized initial dissolution rate of
(I, II, III,IV) carbamazepine was in the
order of form III>II>dihydrate,
while the order of AUC values
was form I>III>dihydrate. This
difference is due to rapid
transformation of form III to
dihydrate in GI fluids.
19/10/2022 15
16. Conclusion
• Differences in the solubility and melting point must also be assessed and then a
decision can be made to determine which form to progress through to the next
stage.
• Metastable form may lead to a preferential choice of a polymorph other than
stable form .
• The lowest energy polymorph is almost always the most chemically stable form,
and will not convert to another polymorph during storage as drug product.
• Metastable crystalline polymorphs may be less chemically stable crystalline
form but is often possible to improve chemical stability of such forms through
judicious choice of excipients and formulation process as metastable form has
relatively higher solubility.
• As polymorphism can have such serious consequences for the bioavailability of
drugs with low aqueous solubility.
19/10/2022 16
17. References
1. Kadam K.P. and Chavan R.P., “ Evaluation of Various Polymorphs by Different
Techniques and Their Characterization -A Review”, The International Journal Of
Engineering And Science (IJES), Volume 5, Issue 6, Pages-29-34, 2016.
2. Ethiraj T. and Ganeshan V., “Polymorphism in pharmaceutical ingredients- A
review”, World Journal of Pharmacy and Pharmaceutical sciences, Volume 3,
Issue 3,621-633, 2014.
3. Saurabh G. and Kaushal C. “Pharmaceutical Solid Polymorphism in
Abbreviated New Drug Application (ANDA) – A Regulatory Perspective”, Journal
of Chemical and Pharmaceutical Research, 2011, 3(3):6-17.
4. Brittain H. G.., Polymorphism in Pharmaceutical Solids, Marcel Dekker, Inc, Special
Indian edition, pp. 7-19,2008.
19/10/2022 17
18. 5. Bauer J. F. , “Polymorphism—A Critical Consideration in Pharmaceutical Development,
Manufacturing, andStability,” J.Valid.Technol.,pp. 15–23,2008.
6 KarpinskiP.. H.,“Polymorphism of Active Pharmaceutical Ingredients,” Chem.Eng.Technol.,
vol. 29,no. 2, pp. 233–237,2006.
7 Singhal D. and Curatolo W., “Drug polymorphism and dosage form design: a practical
perspective,” Adv.DrugDeliv.Rev.,vol. 56,no. 3, pp. 335–347,2004.
8 Aguiar J. and Zelmer, J. E. “Dissolution behavior of polymorphs of Chloramphenicol
palmitate andMefenamic acid,” J.Pharm.Sci.,vol. 58,no. 8, pp. 983–987,1969.
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