The document discusses critical process parameters for manufacturing solid and softgel drug dosages. It outlines key parameters that must be controlled during various stages of production including granulation, blending, compression, coating, drying and encapsulation. Maintaining control of critical parameters like temperature, time, speed and pressure is essential for a validated manufacturing process and consistent end product quality. Process scale up requires understanding how these parameters impact the process as the scale changes.
Technology Transfer and Scale-up in Pharmaceutical IndustryPranjalWagh1
Transfer of technology is defined as “a logical procedure that controls the transfer of any process together with its documentation and professional expertise between development and manufacture or between manufacture sites”.
In Pharmaceutical Industry, technology transfer refers to the processes that are needed for successful progress from drug discovery to product development to clinical trials to full scale commercialization.
It is basically divided into three phases - Research Phase, Development Phase and Production Phase. The presentation elaborates on the technology transfer taking place in production phase. Production phase mainly concerns with validation studies and scale-up.
Validation studies such as performance qualification, cleaning validation and process validation is carried out by R&D department.
Scale-up involves the use of results obtained from lab studies for designing prototype of a product and pilot plant process, constructing pilot plant and further using pilot plant data for full-scale commercialization.
Working principle of compression machinePrashikHumane
The basic principle behind the tablet compression machine is hydraulic pressure. This pressure is transmitted unreduced through the static fluid. Any externally applied pressure is transmitted via static fluid to all the directions in the same proportion. It also makes it possible to multiply the force as needed.
FDA’s emphasis on quality by design began with the recognition that increased testing does not improve product quality (this has long been recognized in other industries).In order for quality to increase, it must be built into the product. To do this requires understanding how formulation and manufacturing process variables influence product quality.Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
This presentation - Part III in the series- deals with the concepts of critical material attributes, critical process parameters , their linage to the the critical Quality attributes of the Product and Quality Risk Management and its pivotal role in the QbD process.Concepts of control strategy are also discussed briefly.
This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
Technology Transfer and Scale-up in Pharmaceutical IndustryPranjalWagh1
Transfer of technology is defined as “a logical procedure that controls the transfer of any process together with its documentation and professional expertise between development and manufacture or between manufacture sites”.
In Pharmaceutical Industry, technology transfer refers to the processes that are needed for successful progress from drug discovery to product development to clinical trials to full scale commercialization.
It is basically divided into three phases - Research Phase, Development Phase and Production Phase. The presentation elaborates on the technology transfer taking place in production phase. Production phase mainly concerns with validation studies and scale-up.
Validation studies such as performance qualification, cleaning validation and process validation is carried out by R&D department.
Scale-up involves the use of results obtained from lab studies for designing prototype of a product and pilot plant process, constructing pilot plant and further using pilot plant data for full-scale commercialization.
Working principle of compression machinePrashikHumane
The basic principle behind the tablet compression machine is hydraulic pressure. This pressure is transmitted unreduced through the static fluid. Any externally applied pressure is transmitted via static fluid to all the directions in the same proportion. It also makes it possible to multiply the force as needed.
FDA’s emphasis on quality by design began with the recognition that increased testing does not improve product quality (this has long been recognized in other industries).In order for quality to increase, it must be built into the product. To do this requires understanding how formulation and manufacturing process variables influence product quality.Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
This presentation - Part III in the series- deals with the concepts of critical material attributes, critical process parameters , their linage to the the critical Quality attributes of the Product and Quality Risk Management and its pivotal role in the QbD process.Concepts of control strategy are also discussed briefly.
This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
A tablet press is a mechanical device that compresses powder into tablets of uniform size and weight. A tablet press can be used to manufacture tablets of a wide variety of materials, including pharmaceuticals, nutraceuticals, cleaning products, industrial pellets and cosmetics. To form a tablet, the granulated powder material must be metered into a cavity formed by two punches and a die, and then the punches must be pressed together with great force to fuse the material together.
PIC/S is a combine term used for the execution of activities of Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme
harmonize, educate, and update aspects relating to Good Manufacturing Practice among member countries
harmonized relation among regulatory authorities and governments
members
history
role
objective and function
guidlines
IPQC Tests for capsules As per IP, BP & USPPramod Ramane
IPQC- In Process Quality Control Tests for Capsules are
1. Uniformity Of Content
2. Disintigration Test
3. Weight Variation Test
4. Dissolution Test
The tests are with Acceptance limits/Criteria as per Indian Pharmacopoeia (IP), British Pharmacopoeia (BP) & United States Pharmacopoeia (USP)
PROCESSING OF CONTAINERS
A. Glass container
List of inorganic compounds used to impart color in glass
Manufacturing Process of glass
B. Plastics container
Classification of plastics
Manufacturing process of plastic container-
Additives of plastics
B. Metal
2. CLOSURES
Materials used for closures
Types of closures
3. CHILD RESISTANT PACKING
4. TAMPER EVIDENT PACKING
*List of inorganic compounds used to impart color in glass
*Manufacturing process of plastic container-
Injection molding
Extrusion
Composite film manufacturing
Blow molding
Solvent casting
Compression molding
In 1992 FDA approves the following configurations as tamper evident packaging:-
1.Film wrappers 11. Metal/cans
2.Blister package
3.Strip package
4.Bubble pack
5.Shrink seals and bands
6.Foil, paper, plastic pouches
7.Bottle seals
8.Tape seals
9.Breakable caps
10.Aerosol containers
COATING PROCESS : PRINCIPLE : Tablet Coating is the process of a coating composition to a moving bed of tablets with the concurrent use of heated air to facilitate evaporation of solvent . The distribution of coating is accomplished by the movement of tablets either perpendicular or vertical to the application of the coating composition
$ CONTENTS $
#Introduction
#Objective of granulation
#Essential properties of granules
#Mechanism of bond formation
#Mechanism of granule formation
#Method of granulation
#Modern equipments in granulation technology
A Primer on Hard Gelatin Capsule ManufacturingVivek Sinha
31/03/2015
Hard gelatin capsule shells are used as soluble containers for incorporation of drugs or nutritional
supplements, usually in the form of powders, pellets or granules in the healthcare industry. They are
commonly intended for oral administration having its advantages over other dosage forms that are
used widely by pharmaceutical companies to develop different medicaments and ensure stability of
the product throughout the shelf life. Since it serves as a major excipient for the manufacture of
pharmaceutical products, the quality attributes of hard capsule shells is very vital for performance
and stability of the final product.
Pharmaceutical products are categorized as high quality and high risk product administered to fight
various types of acute and chronic illnesses where the performance of the product should be
reproducible every time it is administered. The capsule shell consists of two cylindrical parts i.e. the
cap and body; both are open at one extreme. Other extreme of both is hemispherical; the open end
of cap overlaps the open end of body and maintains a closure with a typical lock system. Hence, it is
very important that the product achieves the label claim as set forth and is not contaminated and
readily available to the patients. Benchmarking of developments and manufacturing processes in the
pharmaceutical industry as against other industries led to the concept of Quality by Design or QbD.
Over the past few years, QbD has gained considerable acceptance throughout pharmaceutical
industry and has been successfully applied. The key quality attributes of capsules that determine the
process ability on the high speed filling machine are the dimensional characteristics and weight
variability.
The potential variations of empty hard capsules as an input material and its potential impact on
finished product quality has been studied and high consistency within the specification of the critical
quality parameters is confirmed. Annual product quality review needs to be performed using defined
sampling size against set of verification criteria. The built-in quality approach begins at the
development stage of new product where even factors impacting the performance of hard capsules
i.e. formulation, filling machine type, etc., is given due consideration. The selection of proper raw
material, the process validations and stability studies are to be conducted for suitability. The process
conditions should be maintained along with appropriate in-process quality checks. Final release of
product can be done by QA after product and document review. The data on process capability,
trends of quality parameters, technical specification and the evaluation procedure should be
maintained and submitted based on the current level of quality standards.
The most common method of drug delivery is oral dosage
form of which tablet and capsule are predominant.
Tablet is more accepted as compared to capsule due to
many reason such as cost, tamper resistance, ease of
handling, ease of identification and manufacturing efficiency.
Tablet compression process understanding is resulted in
development of formulation.
Recent advances in the design of tablet compression
equipment has conducted resulted in higher efficiency,
minimized tablet variation, greater flexibility.
A tablet press is a mechanical device that compresses powder into tablets of uniform size and weight. A tablet press can be used to manufacture tablets of a wide variety of materials, including pharmaceuticals, nutraceuticals, cleaning products, industrial pellets and cosmetics. To form a tablet, the granulated powder material must be metered into a cavity formed by two punches and a die, and then the punches must be pressed together with great force to fuse the material together.
PIC/S is a combine term used for the execution of activities of Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme
harmonize, educate, and update aspects relating to Good Manufacturing Practice among member countries
harmonized relation among regulatory authorities and governments
members
history
role
objective and function
guidlines
IPQC Tests for capsules As per IP, BP & USPPramod Ramane
IPQC- In Process Quality Control Tests for Capsules are
1. Uniformity Of Content
2. Disintigration Test
3. Weight Variation Test
4. Dissolution Test
The tests are with Acceptance limits/Criteria as per Indian Pharmacopoeia (IP), British Pharmacopoeia (BP) & United States Pharmacopoeia (USP)
PROCESSING OF CONTAINERS
A. Glass container
List of inorganic compounds used to impart color in glass
Manufacturing Process of glass
B. Plastics container
Classification of plastics
Manufacturing process of plastic container-
Additives of plastics
B. Metal
2. CLOSURES
Materials used for closures
Types of closures
3. CHILD RESISTANT PACKING
4. TAMPER EVIDENT PACKING
*List of inorganic compounds used to impart color in glass
*Manufacturing process of plastic container-
Injection molding
Extrusion
Composite film manufacturing
Blow molding
Solvent casting
Compression molding
In 1992 FDA approves the following configurations as tamper evident packaging:-
1.Film wrappers 11. Metal/cans
2.Blister package
3.Strip package
4.Bubble pack
5.Shrink seals and bands
6.Foil, paper, plastic pouches
7.Bottle seals
8.Tape seals
9.Breakable caps
10.Aerosol containers
COATING PROCESS : PRINCIPLE : Tablet Coating is the process of a coating composition to a moving bed of tablets with the concurrent use of heated air to facilitate evaporation of solvent . The distribution of coating is accomplished by the movement of tablets either perpendicular or vertical to the application of the coating composition
$ CONTENTS $
#Introduction
#Objective of granulation
#Essential properties of granules
#Mechanism of bond formation
#Mechanism of granule formation
#Method of granulation
#Modern equipments in granulation technology
A Primer on Hard Gelatin Capsule ManufacturingVivek Sinha
31/03/2015
Hard gelatin capsule shells are used as soluble containers for incorporation of drugs or nutritional
supplements, usually in the form of powders, pellets or granules in the healthcare industry. They are
commonly intended for oral administration having its advantages over other dosage forms that are
used widely by pharmaceutical companies to develop different medicaments and ensure stability of
the product throughout the shelf life. Since it serves as a major excipient for the manufacture of
pharmaceutical products, the quality attributes of hard capsule shells is very vital for performance
and stability of the final product.
Pharmaceutical products are categorized as high quality and high risk product administered to fight
various types of acute and chronic illnesses where the performance of the product should be
reproducible every time it is administered. The capsule shell consists of two cylindrical parts i.e. the
cap and body; both are open at one extreme. Other extreme of both is hemispherical; the open end
of cap overlaps the open end of body and maintains a closure with a typical lock system. Hence, it is
very important that the product achieves the label claim as set forth and is not contaminated and
readily available to the patients. Benchmarking of developments and manufacturing processes in the
pharmaceutical industry as against other industries led to the concept of Quality by Design or QbD.
Over the past few years, QbD has gained considerable acceptance throughout pharmaceutical
industry and has been successfully applied. The key quality attributes of capsules that determine the
process ability on the high speed filling machine are the dimensional characteristics and weight
variability.
The potential variations of empty hard capsules as an input material and its potential impact on
finished product quality has been studied and high consistency within the specification of the critical
quality parameters is confirmed. Annual product quality review needs to be performed using defined
sampling size against set of verification criteria. The built-in quality approach begins at the
development stage of new product where even factors impacting the performance of hard capsules
i.e. formulation, filling machine type, etc., is given due consideration. The selection of proper raw
material, the process validations and stability studies are to be conducted for suitability. The process
conditions should be maintained along with appropriate in-process quality checks. Final release of
product can be done by QA after product and document review. The data on process capability,
trends of quality parameters, technical specification and the evaluation procedure should be
maintained and submitted based on the current level of quality standards.
The most common method of drug delivery is oral dosage
form of which tablet and capsule are predominant.
Tablet is more accepted as compared to capsule due to
many reason such as cost, tamper resistance, ease of
handling, ease of identification and manufacturing efficiency.
Tablet compression process understanding is resulted in
development of formulation.
Recent advances in the design of tablet compression
equipment has conducted resulted in higher efficiency,
minimized tablet variation, greater flexibility.
Single-Use Tangential Flow Filtration for Closed ProcessingMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3b7vD60
Closed processing involves use of physical barriers to separate processing fluid from the external environment. This approach reduces capital expenditures and clean room classification while accelerating time to market. This webinar will present a TFF process run in a closed mode.
Closed processing with single-use technologies is a critical enabler for efficient and robust manufacturing for novel modalities as well as continuous biomanufacturing processing. It can also reduce the dependence on classified clean rooms for traditional modalities. This approach helps to mitigate the risk of contamination by adventitious agents while enhancing operator safety.
In this presentation, we discuss the implementation of closed processing for downstream applications and present the design and performance testing of a single use manufacturing-scale tangential flow filtration system to be able to operate in both functionally and fully closed mode.
In this webinar, you will learn:
• The context of closed processing
• Differences between closed and functionally closed processing
• The drivers for adoption
• Its practical implementation to a TFF step
Single-Use Tangential Flow Filtration for Closed ProcessingMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3b7vD60
Closed processing involves use of physical barriers to separate processing fluid from the external environment. This approach reduces capital expenditures and clean room classification while accelerating time to market. This webinar will present a TFF process run in a closed mode.
Closed processing with single-use technologies is a critical enabler for efficient and robust manufacturing for novel modalities as well as continuous biomanufacturing processing. It can also reduce the dependence on classified clean rooms for traditional modalities. This approach helps to mitigate the risk of contamination by adventitious agents while enhancing operator safety.
In this presentation, we discuss the implementation of closed processing for downstream applications and present the design and performance testing of a single use manufacturing-scale tangential flow filtration system to be able to operate in both functionally and fully closed mode.
In this webinar, you will learn:
• The context of closed processing
• Differences between closed and functionally closed processing
• The drivers for adoption
• Its practical implementation to a TFF step
Ablaze is a leading Rotary Evaporator Manufacturer and Supplier, we offer a large capacity commercial rotary vaccum evaporator. The Ablaze Rotary Evaporator system operates under conditions of vacuum or atmosphere.
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
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!
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- 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
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.
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.
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 simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
1. “PROCESS SCALE UP AND CRITICAL CONTROL
PARAMETERS OF PROCESS OF SOLID AND SOFTGEL
DOSAGES”
2. CRITICAL PROCESS PARAMETERSCRITICAL PROCESS PARAMETERS
Control of critical process parameters during processing isControl of critical process parameters during processing is
the basic need of a validated process. If critical parametersthe basic need of a validated process. If critical parameters
will not be controlled, It will contribute to the variability ofwill not be controlled, It will contribute to the variability of
the end productthe end product (TQM)(TQM)
3. MANUFACTURING PROCESS FOR TABLETMANUFACTURING PROCESS FOR TABLET
DOSAGE FORMDOSAGE FORM
TABLET
Granulation
Blending
Compression
Coating
4. Granulation is the process in which powder particles are made to
adhere to form agglomerates called granules
GRANULATIONGRANULATION
Granules being denser than the powder occupy lesser volume per unit weight
therefore they are more convenient for storage and shipment.
For slightly hygroscopic material granulation reduce the possibility of caking.
As granules can absorb more moisture yet retain their flow ability because of
their size
To prevent segregation of the constituents of the mix
To improve the flow properties of the mix
To change the particle size distribution so that bulk density can be improved
To increase apparent density of the powder, Granulation can improve or
modify drug release profile.
WHY GRANULATIONWHY GRANULATION??
5. INITIAL MIXING PARAMETERSINITIAL MIXING PARAMETERS
Capacity of RMG
Mixing Time
Mixing Speed
Capacity of FBP
Mixing Time
CFM OF Blower
Capacity of Blender
Mixing Time
Blender RPM
Mixing
RMG FBP BLENDER
6. DRY GRANULATIONDRY GRANULATION
• Sieve /Mesh size.
• Capacity of Blender
• Mixing Time
• Blender Speed (RPM)
• Roller pressure
• Screw feeder RPM
• Pressure roller speed
• % Ratio of fines and granules
Dry Granulation ParametersDry Granulation Parameters
7. WET GRANULATIONWET GRANULATION
Wet granulation is the most commonly used method of granulation in
which binder solution is added to the dry mix
Mechanisms of Granules Formation
Nucleation:Nucleation: Granulation starts with particle to particle contact andGranulation starts with particle to particle contact and
adhesion due to liquid bridges .Number of particles will join to formadhesion due to liquid bridges .Number of particles will join to form
the pendular statethe pendular state
Transition:Transition: Nuclei can grow in two possible ways Either singleNuclei can grow in two possible ways Either single
particles can be added to the nuclei by pendular bridges or two orparticles can be added to the nuclei by pendular bridges or two or
more nuclei may combine the combined nuclei will be reshaped by themore nuclei may combine the combined nuclei will be reshaped by the
agitation of the bedagitation of the bed
Ball Growth:Ball Growth: Granule growth produces large spherical granules andGranule growth produces large spherical granules and
the mean particle size of the granulating system will increase withthe mean particle size of the granulating system will increase with
time and agitationtime and agitation
8. CRITICAL PARAMETERS DURING BINDERCRITICAL PARAMETERS DURING BINDER
PREPARATIONPREPARATION
Temperature of binder solution
Capacity of Paste kettle
Total time taken for preparation of
binder solution
Viscosity of binder if required
9. WET GRANULATION PARAMETERWET GRANULATION PARAMETER
Capacity of FBP
CFM OF Blower
Product Temperature
Peristaltic Pump RPM
Flow rate/Spray Pattern
Atomizing air pressure
Inlet Air Temperature
Mass MixerFBP/FBD
Capacity of RMG
Mixer speed /Chopper
speed
Binder addition time
Effective kneading time
Amperage load of
mixer/Chopper
Capacity of Mass Mixer
Binder addition time
Mixing Time
Mixer Speed
RMG
Wet Granulation
10. ONE-POT TECHNOLOGYONE-POT TECHNOLOGY
Mixing, Granulating and Drying in ONE
processing vessel In one-Pot technology
mixing, granulation and drying options
integrated into one processing vessel
One-Pot Processing option:
Application of a vacuum within the bowl to
dry the wet mass allows drying of
pharmaceutical compounds at low
temperature
11. • The vacuum drying process can be enhanced by the
addition of a small amount of gas (Transflo™), passing
through the product during the drying phase resulting
in shorter drying times and lower residual moisture
content of the final product
• To further enhance the drying process, microwaves
should be added as an additional energy source -
microwave drying is the fastest drying technique
available in One-Pot processing
• Through accurate control of product temperature and
absorbed / reflected microwave power, this technology
is ideal for fast processing of pharmaceutical product
and is the unique one-pot process allowing higher
‘Product Quality’ & direct ‘Scale Up’
ONE-POT TECHNOLOGYONE-POT TECHNOLOGY
12. CRITICAL PARAMETERS DURING DRYINGCRITICAL PARAMETERS DURING DRYING
Inlet air temperature
Outlet air temperature
Bed temperature
Exhaust flap opening /CFM
Drying time
LOD of granules (After complete
drying)
13. CRITICAL PARAMETERS DURING BLENDINGCRITICAL PARAMETERS DURING BLENDING
/MIXING/MIXING
Blending/Mixing
Type of blender/Mixer
Capacity of Blender/Mixer
Blender RPM
Blending time
14. CRITICAL PARAMETERS DURINGCRITICAL PARAMETERS DURING
COMPRESSIONCOMPRESSION
Speed of machine
Compression force
Type of Feeder
Feeder speed
Tablet weight
Tablet thickness
Tablet hardness
Tablet DT
Tablet friability
Tablet diameter/shape
15. Spray Drying ProcessSpray Drying Process
Spray drying is a very fast method of dryingSpray drying is a very fast method of drying
due to the very large surface area created bydue to the very large surface area created by
the atomization of the liquid feed. As athe atomization of the liquid feed. As a
consequence, high heat transfer coefficientsconsequence, high heat transfer coefficients
are generated and the fast stabilisation of theare generated and the fast stabilisation of the
feed at moderate temperatures makes thisfeed at moderate temperatures makes this
method very attractive for heat sensitivemethod very attractive for heat sensitive
materials.materials.
SPRAY DRYING PROCESSOR
16. Spray Drying ProcessSpray Drying Process
There are four basic stages of the spray drying technique:There are four basic stages of the spray drying technique:
1.1.AtomizationAtomization:: A liquid feed stock is atomized into dropletsA liquid feed stock is atomized into droplets
via either a nozzle or a rotary atomizer. Nozzles usevia either a nozzle or a rotary atomizer. Nozzles use
pressure or compressed gas to atomize the feed while apressure or compressed gas to atomize the feed while a
rotary atomiser use a wheel rotating at high speed.rotary atomiser use a wheel rotating at high speed.
2.2.DryingDrying:: Heated process gas (air or nitrogen) is broughtHeated process gas (air or nitrogen) is brought
into contact with the atomized feed using a gas disperser –into contact with the atomized feed using a gas disperser –
leading to evaporation.leading to evaporation.
3.3.Particle formationParticle formation:: As the liquid rapidly evaporates fromAs the liquid rapidly evaporates from
the droplet, a particle forms and falls to the bottom of thethe droplet, a particle forms and falls to the bottom of the
chamber.chamber.
4.4.RecoveryRecovery:: The powder is recovered from the exhaustThe powder is recovered from the exhaust
gases using a cyclone or bag filter. The whole processgases using a cyclone or bag filter. The whole process
generally takes no more than a few seconds.generally takes no more than a few seconds.
17. Fluid Bed
Drying
Tablet
Compression
Dry Mill
Granulation
Dispensing
Dry Mill
Granulation/ Drying
Wet Mill
SOLID DOSAGE PROCESSING: CONTAINED MATERIALS HANDLING
Containment is the area separation from Product to
Personal/ Environmental area by a barrier to prevent
contamination from one area into the other.
18. In-depth understanding of containment requirementsIn-depth understanding of containment requirements
Knowledge of the specific needs both in primary andKnowledge of the specific needs both in primary and
secondary productionsecondary production
t [ h ]
RDI2
RDI1
1 2 3 4 5 6 7 8
ADI
tabletting control granul. control tabletting
Have you ever calculated the real operator exposure?
19. For the pharmaceutical Industry the productFor the pharmaceutical Industry the product
specific limit for the accepted daily exposure tospecific limit for the accepted daily exposure to
the operator of this product is the OELthe operator of this product is the OEL
(Occupational Exposure Limit)(Occupational Exposure Limit)
Calculation of the OEL:Calculation of the OEL: OEL = NOELOEL = NOEL (mg/kg/day) x BW (kg)(mg/kg/day) x BW (kg)
V (m³/day) x SF1 x SF2 xV (m³/day) x SF1 x SF2 x ……
100%
0%
% reacting individuals
pharmacological effect
NOEL (No Observable Effect Level)
toxicological effect
ED50
50% LD50
Dosage (mg/kg/day)
therapeutical
window
Key:
OEL = Occupational Exposure Limit
NOEL = No Observable
Effect Level
BW = Body Weight
V = Breathing Volume
SF = Safety Factor
Examples:
OEL - Paracetamol = 10 mg/m³
OEL - Ethinyl Estradiol = 0.035
µg/m3
20. CRITICAL PARAMETERS DURING COATINGCRITICAL PARAMETERS DURING COATING
Inlet air temperature
Outlet / exhaust air temperature
Bed Temperature
PAN RPM
Pump RPM /Flow rate /Spray Pattern
Atomizing air pressure
Spray Gun Distance to the Bed
Weight gain / % Weight build up
23. CRITICAL PARAMETERS DURING GELMASSCRITICAL PARAMETERS DURING GELMASS
PREPRATIONPREPRATION
Reactor Capacity
Mixer Speed (RPM)
Hot Water Temperature
Vacuum
Mixing Time
Temperature of Gelatin
Storage Vessel
24. CRITICAL PARAMETERS DURINGCRITICAL PARAMETERS DURING
ENCAPSULATIONENCAPSULATION
Die Size
Machine Speed (Die roll RPM)
Gelatin Ribbon thickness
Drum Cooling air Temperature
Capsule Sealing / wedge Temperature
Spreader Box Temperature
Gravity Feed Pipes Temperature
Die Roll Pressure
Environmental Monitoring (Temp. & RH)
25. CRITICAL PARAMETERS DURING DRYINGCRITICAL PARAMETERS DURING DRYING
• Temperature and RH are criticalTemperature and RH are critical
parameters during drying ofparameters during drying of
soft gelatin capsule.soft gelatin capsule.
• For drying of Soft gelatin capsuleFor drying of Soft gelatin capsule
specially designed drying area isspecially designed drying area is
being used in which temperaturebeing used in which temperature
in maintained below 25ºC and %in maintained below 25ºC and %
RH NMT 30%RH NMT 30%