This document discusses techniques for scaling up solid dosage form production from pilot plants. It covers key steps like material handling, blending, granulation, drying, particle size reduction, slugging, compression, coating and capsule filling. For each step, parameters important for process control are identified, such as equipment type, material properties, loading amounts, time, temperature and humidity settings. The goal of scaling up is to control these parameters to consistently produce quality products at larger volumes.
Pilot plant Techniques and Product consideration for liquid dosage forms.D.R. Chandravanshi
CONTENTS:-
DEFINITION
INTRODUCTION
OBJECTIVES
LIQUID DOSAGE FORM
STEPS INVOLVED IN PILOT PLANT FOR ORAL LIQUID
GENERAL CONSIDERATION
Reporting responsibility
Personal requirements
Space requirements
Review of formula
Raw materials
Relevant processing equipments
Process evaluation
GMP consideration
Assurance
PILOT PLANT SCALE UP FOR SUSPENSION
PILOT PLANT SCALE UP FOR EMULSION
REFERENCES
Pilot Plant:-
“Defined as a part of pharmaceutical industry where a lab scale formula is transformed into viable product by the development of liable practical procedure for manufacture”.
Scale-up:-
“The art of designing of prototype using the data obtained from the pilot plant model”
Granularity of Technology Transfer Process, Documentation, Premises and equipment Qualification and Validation. Premises and equipments. Quality control: Analytical Method Transfer. Qualification and Validation
Quality management systems - INDUSTRIAL PHARMACY llJafarali Masi
syllabus
Quality management & Certifications: Concept of Quality, Total Quality Management, Quality by Design (QbD), Six Sigma concept, Out of Specifications (OOS), Change control, Introduction to ISO 9000 series of quality systems standards, ISO 14000, NABL, GLP
Pilot plant Techniques and Product consideration for liquid dosage forms.D.R. Chandravanshi
CONTENTS:-
DEFINITION
INTRODUCTION
OBJECTIVES
LIQUID DOSAGE FORM
STEPS INVOLVED IN PILOT PLANT FOR ORAL LIQUID
GENERAL CONSIDERATION
Reporting responsibility
Personal requirements
Space requirements
Review of formula
Raw materials
Relevant processing equipments
Process evaluation
GMP consideration
Assurance
PILOT PLANT SCALE UP FOR SUSPENSION
PILOT PLANT SCALE UP FOR EMULSION
REFERENCES
Pilot Plant:-
“Defined as a part of pharmaceutical industry where a lab scale formula is transformed into viable product by the development of liable practical procedure for manufacture”.
Scale-up:-
“The art of designing of prototype using the data obtained from the pilot plant model”
Granularity of Technology Transfer Process, Documentation, Premises and equipment Qualification and Validation. Premises and equipments. Quality control: Analytical Method Transfer. Qualification and Validation
Quality management systems - INDUSTRIAL PHARMACY llJafarali Masi
syllabus
Quality management & Certifications: Concept of Quality, Total Quality Management, Quality by Design (QbD), Six Sigma concept, Out of Specifications (OOS), Change control, Introduction to ISO 9000 series of quality systems standards, ISO 14000, NABL, GLP
COPP/CPP it certification of pharmaceutical product for reviewing QSE i.e. Quality, Sefty,Efficacy of product. it important certification for exporting it may required by importing country.
This is the topic related to Product development and technology transfer. In this we will learn how the technology is transferred from R&D department to production department in Pharmaceutical company
COPP/CPP it certification of pharmaceutical product for reviewing QSE i.e. Quality, Sefty,Efficacy of product. it important certification for exporting it may required by importing country.
This is the topic related to Product development and technology transfer. In this we will learn how the technology is transferred from R&D department to production department in Pharmaceutical company
Pilot Plant Scale Up Techniques Used in Pharmaceutical Manufacturing, Prof. Dr. Basavaraj K. Nanjwade, KLE University College of Pharmacy, Belgaum/Belagavi
An overview on the chapter: "Batch Size Increase in Dry Blending and Mixing " from "Pharmaceutical Process Scale-up" book by Michael Levin, chapter by:Albert W. Alexander and Fernando J. Muzzio .
This chapter focuses on scaling up a powder blending process in a tumbling blender and introduces different mathematical approaches to this.
INTRODUCTION
Conventional oral drug delivery systems are known to provide an immediate release of drug, in which one cannot control the release of the drug and effective concentration at the target site. The bioavailability of drug from these formulations may vary significantly, depending on factors such as physico-chemical properties of the drug, presence of excipients, various physiological factors such as the presence or absence of food, pH of the GI tract, GI motility, etc. so to overcome this limitation oral route is replied by parenteral route. This route offers the advantage of reduced dose, targeting of site and avoiding GI stability, hepatic by-pass of drug molecule. (1)
In recent years, much attention has focused on novel drug delivery systems (NDDS). There are many designing options available to control or modify the drug release from a dosage form. Numerous technologies have been used to control the systemic delivery of drugs.
Based on the mechanism of the drug release can be classified as:
Diffusion controlled (matrix and reservoir type of systems)
Dissolution controlled (surface eroding, surface swelling type of systems)
Osmotic drug delivery
Multi particulate systems
Enteric coated (pH dependent systems)
One of the most interesting one is that employs osmotic pressure as an energy source for release of drugs.
The role of drug development is to take a therapeutically effective molecule with sub-optimal physicochemical and/or physiological properties and develop an optimized product that will still be therapeutically effective with additional benefits such as:
Sustained and consistent blood levels within the therapeutic window
Enhanced bioavailability
Reduced interpatient variability
Customized delivery profiles
Decreased dosing frequency
Improved patient compliance
Reduced side effects.
Osmotically controlled oral drug delivery systems (OCODDS) utilize osmotic pressure as the energy source for the controlled delivery of drugs. Drug release from these systems is independent of pH and hydrodynamic conditions of the gastro-intestinal tract (GIT) to a large extent and release characteristics can be easily adjusted by optimizing the parameters of the delivery system.
PRINCIPLE
The flow of solvent depends on SPM characteristics and different osmosis pressures between two sides of regions.
Osmosis pressure for concentrated solution of soluble solutes commonly used in controlled release formulation are extremely high, ranging from 30 atm for sodium phosphate up to 500 atm for a lactose-fructose mixture (US patent number 4077407). These osmosis pressures can produce high water flows across semi permeable membrane.
TYPES OF PUMPS
Oral Osmotic Pumps
Elementary osmotic pump(8)
Push Pull Osmotic Pump(9)
Controlled porosity Osmotic Pumps (CPOP)(10)
OROS CT System(11)
NEED OF THE STUDY
Present investigation is to develop controlled osmotic tablet of
Abstract: The main objective of present investigation is to formulate the sustained release
tablet of Rosiglitazone Maleate using 32 factorial design. Rosiglitazone Maleate, an oral antidiabetic
agent. The SR tablets of Rosiglitazone Maleate were prepared employing different
concentrations of HPMCK15M and Carboplol934P in different combinations as a rate
retardants by Direct Compression technique using 32 factorial design. The quantity/
concentration of Polymers , HPMCK15M and Carboplol934P required to achieve the desired
drug release was selected as independent variables, X1 and X2 respectively whereas, time
required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were
selected as dependent variables. Totally nine formulations were designed and are evaluated
for hardness, friability, thickness, % drug content, In-vitro drug release. From the Results it
was concluded that all the formulation were found to be with in the Pharmacopoeial limits
and the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic
models, the statistical parameters like intercept (a), slope (b) & regression coefficient (r)
were calculated. Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of
developed polynomial equations were verified by designing 2 check point formulations(C1,
C2). According to SUPAC guidelines the formulation (F5) containing combination of 25%
HPMCK15M and 20% Carboplol934P, is the most similar formulation (similarity factor
f2=93.1376, dissimilarity factor f1= 1.7642 & No significant difference, t= 0.06949) to
marketed product (AVANDIA). The selected formulation (F5) follows Higuchi’s kinetics,
and the mechanism of drug release was found to be Fickian Diffusion (n= 0.417).
A provider of contract pharma services in high potent manufacturing, Alkermes Contract Pharma Services, outlines here some of the elements that should be considered by a Sponsor/Donor Pharmaceutical company when outsourcing secondary processing (i.e. dosage form transfer, scale-up and commercial manufacture) of a highly potent product.
The role of dissolution in the demonstration of bioequivalenceinemet
PharmaCon2007 Congress, Dubrovnik, Croatia "New Technologies and Trends in Pharmacy, Pharmaceutical Industry and Education" http://www.pharmacon2007.com
Abstract is available at http://www.pharmaconnectme.com
It is the part of the pharmaceutical industry where a lab scale formula is transformed into a viable product by development of liable and practical procedure of manufacture.
Pilot plant scaleup techniques | unit 1 | Industrial pharmacyFirst name Last name
General considerations-including
significance of personnel requirements, space requirements, raw materials,Pilot plant scale up
considerations for solids, liquid orals, semi solids and relevant documentation,
SUPAC guidelines,Introduction to platform technology
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Pilot plant scale up techniques for solid dosage forms
1. Pilot Plant Scale-Up Techniques
for Solid Dosage Forms
Presented by:
Elaheh Entezar-Almahdi, Pharm-D
Ph.D Candidate of Pharmaceutics, Shiraz University of Medical Sciences
April 2016
2. References
1) The Theory and Practice of Industrial Pharmacy, Lachman, L. Lieberman, H. Kanig, J.
(1986).
2) Pharmaceutics, The Science of Dosage Form Design, Aulton, M. 2nd edition. (2002).
3) Pharmaceutical Dosage Forms Tablets, Vol. 1-3, Lachman, L. Lieberman, H. Schwartz, J.
(1989).
4) Yu LX. Pharmaceutical quality by design: product and process development, understanding,
and control. Pharm Res. 2008;25(4):781-91.
2
3. QbT vs. QbD paradigms
3
QbTQbD
Some of the QbD elements may
include:
- Define target product quality
profile
- Design and develop product and
manufacturing processes
- Identify critical quality attributes,
process parameters, and sources of
variability
- Control manufacturing processes
to produce consistent quality over
time
4. 1. Material Handling
Laboratory scale
Large scale
Lifting and tilting drum
More sophisticated methods (vacuum loading system, screw feed system, and metering
pump)
If the system is used to transfer materials for more than one product, steps must be taken to
prevent cross-contamination by the use of validated cleaning procedures for the equipment.
4
5. 2. Blending
Powders to be used for
encapsulation, or to be granulated
prior to tabletting or encapsulation,
must be well blended to ensure good
drug distribution.
Inadequate blending at this stage
could result in drug content
uniformity variation, especially if the
tablet or capsule is small and the drug
concentration is relatively low in the
blend.
Ingredients should be free of lumps
and agglomerates, otherwise it could
cause flow problem.
5
6. Cont’D
Overloading in blender
Retards the free flow of granules
Reduce the efficiency
Cause content un-uniformity
If the load is to small
Powder blend slides rather than roll in
blender
Improper mixing
6
7. Some Industrial Equipment for Mixing
7
Process parameters:
- Type and geometry of mixer
- Order of addition
- Mixer load level
- Number of rotation (time and
speed)
- Agitation bar (on/off pattern)
8. 3. Granulations
To improve the flow properties
To increase the apparent
density of the powders
To change the particle size
distribution so that the binding
properties on compaction can
be improved
Use of the granulation process
to disperse an active ingredient
Reasons
Types
Wet granulation
Direct compression
method
Dry granulation
8
Process parameters for wet granulation:
- High shear granulation
- Pre-binder addition mix time
- Impeller speed, configuration, and location
- Chopper speed, configuration
- Spray nozzle type and location
- Method of binder addition
- Binder fluid temperature
- Binder addition rate and time
- Post granulation mix time
- Bowel temperature
- Fluid bed granulation
- Mixing time
- Spray nozzle
- Method of binder addition
- Binder fluid temperature
- Binder fluid addition rate and time
- Inlet air flow rate, volume, temperature and
dew point
- Exhaust air temperature
- Filter properties and size
- Shaking intervals
- Product temperature
9. Multifunctional “processor”
9
Dry blending, wet granulation, drying, sizing, and lubrication in a continuous process in a single piece of
equipment
The advantages to using such equipment during scale-up of a product can be significant in terms of space
and manpower requirements. Closed continuous systems have the added advantage of materials, thereby
reducing the danger of personnel exposure to potent materials. This is especially important when potent
and potentially hazardous compounds are involved.
10. 4. drying
10
Hot Air Oven
• Air temperature
• Rate of air flow
• Depth of granulation on the trays
Fluidized Bed Dryer
• Optimum loads
• Rate of airflow
• Inlet air temperature
• Humidity
Data used for small-scale batches (1 to 5 kg)
cannot be used to extrapolate processing
conditions for intermediate-scale (100 kg) or
larger batches.
11. 5. Reduction of particle size
Particle size and especially particle size distribution
are important to the compression characteristics of a
granulation.
Compression factors that may be affected by the
particle size distribution are flowability,
compressibility, uniformity of tablet weight, content
uniformity, tablet hardness and tablet color
uniformity.
Equipment: Oscillating granulator, Hammer mill,
Screening device
11
12. 5. Reduction of particle size (cont’D)
Too large particle size result in: Weight variation and Mottling
Too fine particle size result in: Weight variation, Capping and Lamination
Both oversized and undersized granulation can adversely affect tablet content uniformity.
Lubricants and glidants are added at final blend.
12
Process parameters:
- impact/cutting/screening mills
Mill type
Speed
Blade configuration and type
Screen size and type
Feeding rate
13. 7. Slugging
A dry powder blend that cannot be directly compressed because of
poor flow or compression properties may in some instances be
processed using a slugging operation.
Materials of very low density require roller compaction to achieve
a bulk density sufficient to allow encapsulation or compression.
13
14. 8. Compression
The ultimate test of a tablet formulation and granulation process is whether the granulation
can be compressed on a high-speed tablet press.
Steps involved during compression:
1. Filling of empty die cavity with granulation.
2. Precompression of granulation (optional)***.
3. Compression of granulation.
4. Ejection of the tablet from the die cavity and take-off of compressed tablet
*** courtoy has developed a tablet press that is capable of minimizing capping by a unique
compression system. Instead of the pressure profile being the customery sine wave, it becomes
more of a square wave.
14
15. 15
Process parameters:
- Compression speed and force
- Pre-compression force
- Feed frame type and speed
- Hopper design, height, and vibration
- Tablet weight and thickness
- Depth of fill
- Punch penetration depth
16. Tablet Coating
Equipment: Conventional coating pan, perforated pans
or fluidized-bed coating column
Types: sugar coating, film coating
Tablets must be sufficiently hard to withstand the
tumbling.
Conditions: optimum tablet load, operating tablet, bed
temperature, drying air flow rate, temperature, solution
application rate
16
Process parameters:
- Product temperature
- Spray nozzle (type, quantity, pattern,
configuration
- Individual gun spray rate
- Total spray rate
- Pan rotation speed
- Atomization air pressure
- Pattern air pressure
- Inlet air flow, temperature, dew point
- Exhaust air temperature, air flow
- Total coating time
17. Capsules
To produce capsules on high-speed equipment, the
powder blend must have:
Uniform particle size distribution
Bulk density
Compressibility required to promote good flow
characteristics
equipment:
Zanasi or Martelli form slugs in a dosator ( a hollow
tube with a plunger to eject the capsule plug)
Hoflinger-Karg --- Tamping pins
17
18. Cont’D
Overly lubricated granules---- delaying capsule disintegration and dissolution
Granulation moisture content can be important to chemical or physical stability of the
finished product.
Empty gelatin capsule have a recommended storage condition of 15 to 25 degree and a RH
of between 35 and 65%.
High humidity conditions--- the capsules may swell because of the moisture absorbed.
Low humidity conditions--- the capsules may brittle and increase their static charge.
18