The document discusses various types of impurities that can be present in pharmaceutical products, including organic, inorganic, and residual solvent impurities. It describes potential sources of impurities such as starting materials, reagents, catalysts, and degradation processes. It also discusses genotoxic impurities and establishes a five-class system for categorizing them based on their known or suspected toxicity and carcinogenic properties.
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]Shikha Popali
THE CHEMISTRY OF PEPTIDES THE DIFFICULT TO COLLECT DATA FOR READERS , THREFORE HERE WE HAVE COLLECTED ALL THE DATA AT A PLACE AND PROVIDED EASIER TO CHEMISTRIANS.
Process chemistry AS PER PCI SYLLABUS FOR M.PHARMShikha Popali
pharmaceutical process chemistry is process WHERE FROM THE RESEARCH TO FINISH PRODUCT INCLUDING THE PRODUCT DEVELOPMENT AT LABORATORY LEVEL THAN PILOT PLANT WHERE THE PRODUCT IS MANUFACTURED IN 10X THAN FINAL AT 100X THAT IS SCALE UP PLANT.
Stages of scale up process mparm 1st year pharmaceutical process chemistryDhanashreeSarwan
Define Scale up process, need of Scale up technique, Stages of scale up process Bench\lab scale, pilot plant, large scale up technique, validation of large scale up process
CHEMISTRY OF PEPTIDES [M.PHARM, M.SC, BSC, B.PHARM]Shikha Popali
THE CHEMISTRY OF PEPTIDES THE DIFFICULT TO COLLECT DATA FOR READERS , THREFORE HERE WE HAVE COLLECTED ALL THE DATA AT A PLACE AND PROVIDED EASIER TO CHEMISTRIANS.
Process chemistry AS PER PCI SYLLABUS FOR M.PHARMShikha Popali
pharmaceutical process chemistry is process WHERE FROM THE RESEARCH TO FINISH PRODUCT INCLUDING THE PRODUCT DEVELOPMENT AT LABORATORY LEVEL THAN PILOT PLANT WHERE THE PRODUCT IS MANUFACTURED IN 10X THAN FINAL AT 100X THAT IS SCALE UP PLANT.
Stages of scale up process mparm 1st year pharmaceutical process chemistryDhanashreeSarwan
Define Scale up process, need of Scale up technique, Stages of scale up process Bench\lab scale, pilot plant, large scale up technique, validation of large scale up process
Chemistry of peptide (BPHARM,MPHARM,MSC,BSC)Shikha Popali
THE PRESENTATION DESCRIBING BOND FORMATION OF AMINO ACIDS AND PROTEINS AND COUPLING REAGENTS IN PEPTIDE SYNTHESIS FOLLOWED BY CARBODIMIDES, PHOSPHONIUM AND AMMONIUM SALTS.
OXIDATION [PHARMACEUTICAL PROCESS CHEMISTRY]Shikha Popali
INTRODUCTION TO OXIDATION , WHICH IS PROCESS OF ADDITION OF OXYGEN TO THE COMPOUND IN RPOCESS CHEMISTRY AND LIQUID PHASE OXIDATION AND OTHER OXIDISING AGENTS ARE DISCUSSED.
UNIT OPERATIONS (unit 2) pharmaceutical process chemistrySaketChoudhary13
its a presentation on the 2nd unit of pharmaceutical process chemistry which include extraction ,filtration and steam distillation and azeotropic distillation
New Microsoft PowerPoint Presentation.pptxKrishna2017
The impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product; but they can also be brought into the drug product through the formulation process or by contact with packaging of the various impurities that can be found in drug products.
Chemistry of peptide (BPHARM,MPHARM,MSC,BSC)Shikha Popali
THE PRESENTATION DESCRIBING BOND FORMATION OF AMINO ACIDS AND PROTEINS AND COUPLING REAGENTS IN PEPTIDE SYNTHESIS FOLLOWED BY CARBODIMIDES, PHOSPHONIUM AND AMMONIUM SALTS.
OXIDATION [PHARMACEUTICAL PROCESS CHEMISTRY]Shikha Popali
INTRODUCTION TO OXIDATION , WHICH IS PROCESS OF ADDITION OF OXYGEN TO THE COMPOUND IN RPOCESS CHEMISTRY AND LIQUID PHASE OXIDATION AND OTHER OXIDISING AGENTS ARE DISCUSSED.
UNIT OPERATIONS (unit 2) pharmaceutical process chemistrySaketChoudhary13
its a presentation on the 2nd unit of pharmaceutical process chemistry which include extraction ,filtration and steam distillation and azeotropic distillation
New Microsoft PowerPoint Presentation.pptxKrishna2017
The impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product; but they can also be brought into the drug product through the formulation process or by contact with packaging of the various impurities that can be found in drug products.
Introduction,Drug- Excipient Compatibility Experimental Design ,Excipient role in drug destabilization,DRUG EXCIPIENT COMPATIBILTY IN PARENTERAL PRODUCTS.This topic are described.
Just providing the information on Impurities in drug substances & Drug products to share my view and the collected information from the web for knowledge purpose.
drug execipent compatibilty studies is of prime importance for the better formulation of the new drug and also for reducing cost by verfication of the data at the earlier atage.
this presentation will give the brief explanation of the goal, importance, dteps involve to studi the drug execient compatibility studies with different examples suitable accordiingly.
" Stability testing is an essential part of the process of ensuring that the patient receives a product that meets established standards of safety, efficacy and quality."
Content :
* USP Definition of Stability.
* The Five Types of Stability.
* Factors affecting stability.
* Stability studies in manufacturing.
* Observing products for evidence of instability.
* Responsibility of the pharmacist.
Reference : USP – United States Pharmacopeia, 2008.
{1191} Stability consideration in dispensing practice/ General information, page 2414.
ICH Q3AR2 explained - impurities in drug substancesKiran Nivedh
This presentation explains ICH guideline - Q3AR2 in an understandable way by giving examples.
How to impart in the dossier, format for writing impurities in drug substance is given in the book:
1. https://www.scribd.com/book/429190300/Impurities-In-Drug-Substances-ICH-Explained
2. https://www.smashwords.com/books/view/961598
a small book explaining ICH guidelines - impurities in new drug substances with examples
also available in
https://books2search.com/impurities-in-drug-substances-ich-explained-9780463960592
https://www.chapters.indigo.ca/en-ca/books/contributor/author/kiran-nivedh/
It defines impurities and classifies them as organic, inorganic, or residual solvents. Organic impurities can arise from starting materials, degradation, or during formulation. Inorganic impurities may come from reagents, heavy metals, or filtering aids. Residual solvents must meet ICH limits for patient safety.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with basics impurity profiling and degradent characterization.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
biotransformation of drug
Biotransformation/Xenobiotic metabolism/ drug metabolism/detoxification.
-Xenobiotics: a wide variety of foreign compounds to which humans get exposed in day to day life.
-It includes unknown compounds, drugs, environmental pollutants, toxins.
-Many xenobiotics can evoke biological responses.
DEFINITION
The biochemical alteration of drug or xenobiotic in the presence of various enzymes that acts as a catalyst which themselves not consumed in the reaction and there by may activate or deactivate the drug is called biotransformation.
Why Biotransformation is necessary?:
To easily eliminate the drug
To terminate drug action by inactivating it
Consequences of Biotransformation
Active to Inactive:
Phenobarbitone---- Hydroxyphenobarbitone
Inactive (prodrug) to Active :
L-Dopa ---- Dopamine
Parathion -- Paraoxon
Talampicillin -- Ampicillin
Active to equally active:
Diazepam -- Oxazepam
Amitriptyline -- Nortriptyline
Imipramine -- Des-imipramine
Codeine -- Morphine
Sites of biotransformation
In the body: Liver, small and large intestines, lungs, skin, kidney, nasal mucosa & brain.
Liver is considered “metabolite clearing house” for both endogenous substances and xenobiotics.
Intestines are considered “initial site of drug metabolism”.
FIRST PASS METABOLISM:
First pass metabolism or presystemic
metabolism or ‘first pass effect’
After oral administeration many drugs are absorbed from the small intestine - transported first via portal system to the liver, where they undergo extensive metabolism before reaching systemic circulation.
fundamental concepts in drug biotransformation
Lipid soluble drugs are poorly excreted in the urine. They tend to store in fat and/or circulate until they are converted (phase I biotransformation) to more water soluble metabolites or metabolites that conjugate (phase II biotransformation) with water soluble substances.
Water soluble drugs are more readily excreted in the urine. They may be metabolized, but generally not by the CYP enzyme systems.
Enzymes catalyzing phase I biotransformation reactions
Enzymes catalyzing phase I biotransformation reactions include:
cytochrome P-450
aldehyde and alcohol dehydrogenase
deaminases
esterases
amidases
epoxide hydratases
Addition of water
Cleavage of R-O or R-N bond accompanied by addition of H2O
CYTOCHROME P450
The cytochrome P-450 families are referred to using an arabic numeral, e.g., CYP1, CYP2, etc.
Each family has a number of subfamilies denoted by an upper case letter, e.g., CYP2A, CYP2B, etc.
The individual enzymes within each subfamily are denoted by another arabic numeral, e.g., CYP3A1, CYP3A2, etc.
It is my journal club presentation on Synthesis, Docking Studies and Anticancer Activity of New Substituted Pyrimidine and Triazolopyrimidine Glycosides.
I sincerely thank the authors Wael A. El-Sayed, Ashraf M. Mohamed , Hemat S. Khalaf, Dina S. EL-Kady, May Al-Manawaty
It is my Journal club presentation on Docking studies, synthesis, characterization of some novel Oxazine substituted 9-anilinoacridine derivatives and evaluation for their Antioxidant and Anticancer activities as topoisomerase II inhibitors.
I sincerely thank the authors R. Kalirajan*, Vivek Kulshrestha, S. Sankar, S. Jubie, Department of Pharmaceutical Chemistry, JSS College of Pharmacy, (Off Campus, JSS University, Mysore), Udhagamandalam 643001, Tamilnadu, India
This presentation gives us an information regarding the protease enzyme and its development ,development of agents using molecular modelling techniques
This Powerpoint presentation helps us to know the basic working principles, instrumentation an advantage of super critical fluid chromatography.
Contact Details:
Anbu Dinesh Jayakumar
M.Pharmacy ( Pharmaceutical Chemistry)
Sri Ramakrishna Institute of Paramedical Sciences, Coimbatore
Mobile : 8838404664 / 8608890121( Whatsapp)
Email: anbudinesh007@gmail.com
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
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
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
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
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
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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.
Follow us on: Pinterest
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
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
3. IMPURITIES?
Impurities are chemical substances composed of liquid, gas, or solid,
which differ from the chemical composition of the material or compound.
They are either naturally occurring or added during synthesis of a
chemical / commercial product.
During production, impurities may be purposely, accidentally, added into
the substance.
3
4. Standards have been established for permitted levels of
various impurities in a manufactured product.
A material's level of purity can only be stated as being
more or less pure than some other material.
Inorganic contaminants are not considered as an impurity
unless they are toxic, such as heavy metal or arsenic.
4
5. SOURCES OF IMPURITIES
Majority of the impurities are occurred during the synthetic
route of manufacturing process.
There are several possibilities of synthesizing a drug
It is possible that the same product of different sources may give
rise to different impurities.
5
6. The situation with the organic impurities.
•Toxicity is unknown.
•Not easily predictable.
•For this reason the ICH guidelines set threshold
limit above which the identification of the
impurity is obligatory.
6
7. The number of INORGANIC IMPURITIES and RESIDUAL
SOLVENTS are limited.
• Easily identified.
• Physiological effects and toxicity are well known.
• The limits set by the pharmacopoeias & ICH guidelines
guarantee that the harmful effects of these impurities do not
contribute to the toxicity or the side effects of the drug
substances.
7
9. a) ORGANIC IMPURITIES
Arise during the
manufacturing process
and/or storage of the new
drug substance.
They can be identified or
unidentified, volatile or non-
volatile, and include:
Starting materials By-products Intermediates
Degradation
products
Reagents, ligands
and catalysts
9
10. b) INORGANIC IMPURITIES
Results from the
manufacturing
process.
They are
normally known
and identified and
include:
Reagents, ligands and
catalysts
Heavy metals or other
residual metals
Inorganic salts
Other materials (e.g.,
filter aids, charcoal)
10
11. c) RESIDUAL SOLVENTS
Solvents are
inorganic or organic
liquids.
They are used as vehicles
for the preparation of
solutions or suspensions
in the synthesis of a new
drug substance.
Since these are generally
of known toxicity, the
selection of appropriate
controls is easily
accomplished.
11
12. SOURCES OF ORGANIC IMPURITIES
•Arise during the manufacturing process or storage of the
drug substance.
•These impurities are derived from drug substance
synthetic processes and degradation reactions in drug
substances and drug products.
12
13. SYNTHETIC PROCESS
IMPURITY
DEGRADATION PROCESS
IMPURITY
•Starting materials
•Intermediates
•Reagents
•Ligands
•Catalysts used in the chemical
synthesis
•By-products from the side-
reactions of the chemical
synthesis.
ENANTIOMERIC
IMPURITIES
Degradation products of the
drug substances and drug
products occurs due to storage
or stress conditions
13
15. These synthetic impurities are usually referred to as Process impurities.
The goal is to determine the structures and origins of these impurities.
This knowledge is critical for improving the synthetic chemical process,
in order to eliminate or minimize process impurities.
15
16. a) STARTING MATERIALS & INTERMEDIATES
“Starting materials and intermediates are used to construct the final
form of a drug substance”
Unreacted starting materials and intermediates, involved in the last steps of the synthesis, can
potentially survive the synthetic and purification process and appear in the final product as
impurities.
SYNTHESIS OF TIPRANAVIR
Aniline - Intermediate in the last step of the synthesis.
Due to the similarity between the structures of aniline and the final product, it is
difficult to totally eliminate it in the subsequent purification step.
Consequently, it appears in the drug substance at around 0.1%.
16
17. b) IMPURITIES IN THE STARTING MATERIALS
“Impurities present in the staring materials follows the same reaction
pathways as the starting material itself, and the reaction products could carry
over to the final product as process impurities”
Example :The presence of a 4-trifluoromethyl positional isomer in
3- trifluoromethyl-alpha-ethylbenzhydrol (flumecinol), due to the presence of
4- trifluoromethylbenzene impurity in the starting material, 3-trifluoromethylbenzene.
17
18. c) REAGENTS, LIGANDS AND CATALYSTS
These are less commonly found in APIs.
However, in some cases they may pose a problem as impurities.
Chemical reagents, ligands, and catalysts used in the synthesis of a drug substance can be
carried over to the final products as trace level impurities.
Example:
SYNTHESIS OF A ß LACTAM DRUG SUBSTANCE:
Carbonic acid chloromethyl tetrahydro-pyran-4-yl ester (CCMTHP) - alkylating agent,
was observed in the final product as an impurity.
18
19. “Many chemical reactions are promoted by metal based catalysts”
Example:
A Ziegler-Natta catalyst contains titanium
Grubb’s catalyst contains ruthenium
Adam’s catalyst contains platinum.
In some cases, reagents or catalysts may react with intermediates or final
products to form by-products.
Example:
Pyridine, a catalyst used in the course of synthesis of mazipridone, reacts
with an intermediate to form a pyridinium impurity.
19
20. d) BY-PRODUCTS OF THE SYNTHESIS
By-products can
be formed
through a variety
of side reactions,
such as:
By-products from
the side reactions
are the common
process
impurities in
drugs.
The side-
reactions are
common during
the synthesis of
drug substances.
Chemical
reactions are not
100% selective;
Incomplete reaction ,Over reaction,Isomerisation ,Dimerisation ,Rearrangement
Unwanted reactions of starting materials ,Intermediates with chemical reagents
Catalysts.
20
21. e) PRODUCTS OF OVER-REACTION
“In many cases the previous steps of the syntheses are not selective enough
and the reagents attack the intermediate at the desired site”
Synthesis of Nanodralone decanoate:
-Last step - Decanoylation of the 17-OH group.
-Overreaction:The reagents also attack the 4-ene- 3 oxo group leading to an enol
ester- type impurity (3, 17β- dihydroxyestra-3, 5- diene disdecanoate).
21
22. f) PRODUCTS OF SIDE REACTIONS
Side reactions are unavoidable in drug synthesis.
Side reactions leads to trace level impurities to be detected and
elucidated during impurity profiling.
The formation of diketopiperazine derivative is a typical side reaction
in peptide synthesis.
22
25. IMPURITIES ORIGINATING FROM
DEGRADATION OF THE DRUG SUBSTANCE
Impurities can also be formed by degradation of the end product during
manufacturing of bulk drugs.
Degradation products resulting from storage or formulation to different dosage
forms or aging are common impurities in the medicines.
The definition of degradation product in the ICH guidelines is a molecule
resulting from a chemical change in the substance brought about by overtime
or due to the action of light, temperature, pH / water or by reaction with
excipient and/or the intermediate container closure system.
25
26. Example:
In the case of aspartame, in the presence of moisture, hydrolysis occurs
to form the degradation products L- aspartyl- LPhenyalanine and 3-
benzyl-6-carboxymethyl 2, 5-diketopierazine.
A third degradation product β-L- aspartyl-L-phenylalanine methyl
ester is also known to form.
Aspartame degradation also occurs during prolonged heat treatment.
26
27. The majority of therapeutic chiral drugs used as pure enantiomers are
natural products
High level of Enantio selectivity of their biosynthesis excludes the
presence of enantiomeric impurities
In Synthetic chiral drugs, the racemates which are usually marketed, if
the pure enantiomer is administered, the antipode is considered to be
an impurity.
The reason for its presence can be either the incomplete enantio
selectivity of the syntheses or incomplete resolution of the enantiomers
of the racemate.
ENANTIOMERIC IMPURITY
27
28. ICH guidelines exclude enantiomeric impurities, pharmacopoeias consider
them as ordinary impurities.
A single enantiomeric form of chiral drug is now considered as an
improved chemical entity that may offer a better pharmacological profile
and an increased therapeutic index with a more favourable reaction profile.
However, the pharmacokinetic profile of Levofloxacin (S-Isomeric form)
and Ofloxacin (R- isomeric form) are comparable, suggesting the lack of
advantages of single isomer in this regard.
The prominent single isomer drugs, which are being marketed, include
levofloxacin (S-ofloxacin), levalbuterol (R-albuterol) and esomeprazole
(Someprazole).
28
29. Examples of drugs containing enantiomeric impurities are:
Dexchlorophenarmine maleate (R enantiomer impurity allowed <0.5%)
Timolol maleate (R enantiomer impurity allowed < 1%)
Clopidogrel sulphate (R enantiomer impurity allowed < 1%)
*In general, an individual API may contain all of the above mentioned
types of organic impurities varying from negligible to significant level.
29
31. GENOTOXIC IMPURITIES
The property of chemical agents that damages the genetic information
within a cell causing mutations, which may lead to cancer.
“All mutagens are genotoxic, whereas not all genotoxic substances are
mutagenic”
Genotoxic impurities have also been defined as an “impurity that has been
demonstrated to be genotoxic in an appropriate genotoxicity test model,
e.g., bacterial gene mutation (Ames) test”.
31
32. A FIVE-CLASS SYSTEM FOR CATEGORIZING
GENOTOXIC IMPURITIES
CLASS1: “Impurities known to be genotoxic (mutagenic) and carcinogenic”
It includes known animal carcinogens with reliable data for a
genotoxic mechanism, and human carcinogens.
The genotoxic nature of the impurity is demonstrated using published
data on the chemical structure.
32
33. CLASS2: “Impurities knownto be genotoxic(mutagenic), but with unknown carcinogenic
potential”
It includes impurities with demonstrated mutagenicity based
on testing of the impurity in conventional genotoxicity tests.
CLASS3: “Impurities that havean alerting structure unrelated to thestructureof the API,and of
unknowngenotoxic(mutagenic) potential”
It includes impurities with functional moieties that can be linked to
genotoxicity based on structure
These moieties have not been tested as isolated compounds and are
identified based on chemistry and using SAR.
33
34. CLASS4:
”Impurities with an alerting structure related to the API and impurities that containan alerting
functional moiety that is shared withthe structure of the API”
CLASS5:
No alerting structure or indicationof genotoxic potential.
34