HPMC capsules showed longer opening times than gelatin capsules in dissolution testing. For fast releasing formulations, no major dissolution differences were observed between HPMC and gelatin capsules under normal test conditions. However, the QV HPMC capsule was more sensitive to surfactants like CTAB and ions like potassium. Storage under high heat and humidity did not significantly impact dissolution for any capsule type. No changes were observed after low humidity storage for weeks.
How to Manufacture Detergents Powder, Active Ingredients for Detergents, Surf...Ajjay Kumar Gupta
The Indian detergent industry is about three decades old. An interesting and unique feature of detergent industry in India is the existence of non power operated units which do not use any electrical power for the production of detergent powder. But the production technology of detergents have been changed involving high technique in process control, more skilled personnel and requiring large input.
See more
http://goo.gl/U4s0Ry
http://goo.gl/oFYalm
http://goo.gl/xbbtO0
http://www.entrepreneurindia.co/
Tags
Technology Book on detergent, Active Ingredients for Detergents, Cleaners, components of detergents, Detergent Formulation Consulting In India, Detergent Powder Business, Profitable Small Scale Manufacturing, Detergent Powder Flow sheet, Detergent Powder Ingredients, Detergent Powder Line, Detergent Powder Making Formula, Detergent Powder Making Formula Pdf, Detergent Powder making machine factory, Detergent Powder Making Plant, Detergent Powder Making Process Pdf, Detergent Powder Making Process Video, Detergent Powder Making Raw Material, Detergent Powder Making Small Business Manufacturing, Detergent Powder Manufacturing Industry in India, Detergent Powder Manufacturing Plant, Detergent Powder Manufacturing: Small Business Idea, Detergent Raw Material - Washing Powder Raw Material Suppliers, Enzymatic Detergents Empower, Fabric Wash, Formulation of Detergents, General Wash Powders, Get started in small-scale Detergent Powder manufacturing business, Household Detergent, Household Laundry Detergent Powders, How Laundry Detergent Is Made - Material, Manufacture, Making, How to Make Detergent Powder, How to Manufacture Detergent and Cleaning Products, How to Set Up Start Detergent Powder Manufacturing Business in India, How to Start a Detergent Powder manufacturing business?, How to Start a Powdered Detergent Plant, How to Start Detergent Powder Manufacturing Industry in India, How to Start: Detergent, Washing Powder Business in India, Industrial Detergents, Ingredients - Laundry Detergent – Recipe, Introduction to Detergents, Laundry Care, Laundry Detergent Production, Laundry Detergents Formulation - Chemistry in Surfactants, Liquid Detergents, Manufacturing Detergent Cakes, Manufacturing of Detergent Powder, Most Profitable Detergent Powder Manufacturing Business Ideas,Powder Detergent Manufacturing Process, Setting up and opening your Detergent Powder manufacturing Business, Setting up of Detergent Powder Manufacturing Units, setup a detergent industry, The Product Formulation and Procedure of detergent, Washing Powder Manufacturing Plant, Washing Soap and Detergent, What Is the Production Process for Powder Detergent?, Starting a Detergent Powder Manufacturing Business, Surfactant, Synthetic Detergent, Synthetic-Detergents-Manufacturing Process,
Printing and Writing Inks with Formulae and ProcessesAjjay Kumar Gupta
Ink is a liquid or paste that contains pigments or dyes and is used to colour a surface to produce an image, text, or design. Ink is used for drawing or writing with a pen, brush, or quill. Thicker inks, in paste form, are used extensively in letterpress and lithographic printing. Ink can be a complex medium, composed of solvents, pigments, dyes, resins, lubricants, solubilizers, surfactants, particulate matter, fluorescents, and other materials.
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Printing and Writing Inks with Formulae, Printing and Writing Inks with Processes, A Guide to Popular Printing Techniques, best small and cottage scale industries, formulations of printing inks, Gravure Printing industry, Growth in the Writing inks, How Ink Is Made, How Ink is manufactured, How printing ink manufactured in factory, how to manufacture ink, How to Start a Printing and writing inks Production Business, How to start a successful Printing and writing inks business, How to Start Printing and writing inks Industry in India, Ink and Printability Testing, Inking Rollers, Inking Rollers uses, Manufacture of Inks and varnishes, manufacturing of varnish, Modern Printing Process, Most Profitable Printing and writing inks manufacturing Business Ideas, new small scale ideas in inks manufacturing industry, Newspaper Printing Ink, Packaging Inks Market - Covering the Printing Inks, Coatings and Allied Industries, Printing and writing inks Based Small Scale Industries Projects, Printing and writing inks Business, Printing and writing inks manufacturing Industry in India, Printing and writing inks, manufacturing Projects, printing ink formulation, printing ink manual, Printing Ink Manufacturing, printing ink manufacturing process, Printing Ink Technology and Manufacture, Printing Inks & Applications, Printing Processes and Printing Inks, Printing processes: Offset, Flexo, Digital, Gravure, Profitable Small Scale inks Manufacturing, Robust Growth in the Indian Exports of Printing Inks, screen printing process, Setting up and opening your Printing and writing inks Business, Setting up and opening your Printing Business, Setting up of Printing and writing inks manufacturing Units, Small scale Commercial Printing and writing inks production, Small Scale Printing and writing inks manufacturing Projects, Small Start-up Business Project, Start up India, Stand up India, Starting a Printing and writing inks manufacturing Business, Starting a Printing Business, Starting an Ink and Toner Cartridge Refilling Business, Starting an Offset Printing Press, Start-up Business Plan for Printing and writing inks, startup ideas, Startup Project, Startup Project for Printing and writing inks Business, startup project plan, The manufacturing process of a news ink, varnish making process, Varnish manufacturing, varnish manufacturing process, Web Offset Machines, What Equipment Do I Need to Start a Printing Business?, Writing ink manufacturing process
How to Manufacture Detergents Powder, Active Ingredients for Detergents, Surf...Ajjay Kumar Gupta
The Indian detergent industry is about three decades old. An interesting and unique feature of detergent industry in India is the existence of non power operated units which do not use any electrical power for the production of detergent powder. But the production technology of detergents have been changed involving high technique in process control, more skilled personnel and requiring large input.
See more
http://goo.gl/U4s0Ry
http://goo.gl/oFYalm
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http://www.entrepreneurindia.co/
Tags
Technology Book on detergent, Active Ingredients for Detergents, Cleaners, components of detergents, Detergent Formulation Consulting In India, Detergent Powder Business, Profitable Small Scale Manufacturing, Detergent Powder Flow sheet, Detergent Powder Ingredients, Detergent Powder Line, Detergent Powder Making Formula, Detergent Powder Making Formula Pdf, Detergent Powder making machine factory, Detergent Powder Making Plant, Detergent Powder Making Process Pdf, Detergent Powder Making Process Video, Detergent Powder Making Raw Material, Detergent Powder Making Small Business Manufacturing, Detergent Powder Manufacturing Industry in India, Detergent Powder Manufacturing Plant, Detergent Powder Manufacturing: Small Business Idea, Detergent Raw Material - Washing Powder Raw Material Suppliers, Enzymatic Detergents Empower, Fabric Wash, Formulation of Detergents, General Wash Powders, Get started in small-scale Detergent Powder manufacturing business, Household Detergent, Household Laundry Detergent Powders, How Laundry Detergent Is Made - Material, Manufacture, Making, How to Make Detergent Powder, How to Manufacture Detergent and Cleaning Products, How to Set Up Start Detergent Powder Manufacturing Business in India, How to Start a Detergent Powder manufacturing business?, How to Start a Powdered Detergent Plant, How to Start Detergent Powder Manufacturing Industry in India, How to Start: Detergent, Washing Powder Business in India, Industrial Detergents, Ingredients - Laundry Detergent – Recipe, Introduction to Detergents, Laundry Care, Laundry Detergent Production, Laundry Detergents Formulation - Chemistry in Surfactants, Liquid Detergents, Manufacturing Detergent Cakes, Manufacturing of Detergent Powder, Most Profitable Detergent Powder Manufacturing Business Ideas,Powder Detergent Manufacturing Process, Setting up and opening your Detergent Powder manufacturing Business, Setting up of Detergent Powder Manufacturing Units, setup a detergent industry, The Product Formulation and Procedure of detergent, Washing Powder Manufacturing Plant, Washing Soap and Detergent, What Is the Production Process for Powder Detergent?, Starting a Detergent Powder Manufacturing Business, Surfactant, Synthetic Detergent, Synthetic-Detergents-Manufacturing Process,
Printing and Writing Inks with Formulae and ProcessesAjjay Kumar Gupta
Ink is a liquid or paste that contains pigments or dyes and is used to colour a surface to produce an image, text, or design. Ink is used for drawing or writing with a pen, brush, or quill. Thicker inks, in paste form, are used extensively in letterpress and lithographic printing. Ink can be a complex medium, composed of solvents, pigments, dyes, resins, lubricants, solubilizers, surfactants, particulate matter, fluorescents, and other materials.
Tags
Printing and Writing Inks with Formulae, Printing and Writing Inks with Processes, A Guide to Popular Printing Techniques, best small and cottage scale industries, formulations of printing inks, Gravure Printing industry, Growth in the Writing inks, How Ink Is Made, How Ink is manufactured, How printing ink manufactured in factory, how to manufacture ink, How to Start a Printing and writing inks Production Business, How to start a successful Printing and writing inks business, How to Start Printing and writing inks Industry in India, Ink and Printability Testing, Inking Rollers, Inking Rollers uses, Manufacture of Inks and varnishes, manufacturing of varnish, Modern Printing Process, Most Profitable Printing and writing inks manufacturing Business Ideas, new small scale ideas in inks manufacturing industry, Newspaper Printing Ink, Packaging Inks Market - Covering the Printing Inks, Coatings and Allied Industries, Printing and writing inks Based Small Scale Industries Projects, Printing and writing inks Business, Printing and writing inks manufacturing Industry in India, Printing and writing inks, manufacturing Projects, printing ink formulation, printing ink manual, Printing Ink Manufacturing, printing ink manufacturing process, Printing Ink Technology and Manufacture, Printing Inks & Applications, Printing Processes and Printing Inks, Printing processes: Offset, Flexo, Digital, Gravure, Profitable Small Scale inks Manufacturing, Robust Growth in the Indian Exports of Printing Inks, screen printing process, Setting up and opening your Printing and writing inks Business, Setting up and opening your Printing Business, Setting up of Printing and writing inks manufacturing Units, Small scale Commercial Printing and writing inks production, Small Scale Printing and writing inks manufacturing Projects, Small Start-up Business Project, Start up India, Stand up India, Starting a Printing and writing inks manufacturing Business, Starting a Printing Business, Starting an Ink and Toner Cartridge Refilling Business, Starting an Offset Printing Press, Start-up Business Plan for Printing and writing inks, startup ideas, Startup Project, Startup Project for Printing and writing inks Business, startup project plan, The manufacturing process of a news ink, varnish making process, Varnish manufacturing, varnish manufacturing process, Web Offset Machines, What Equipment Do I Need to Start a Printing Business?, Writing ink manufacturing process
An insight on formulating texture coatings and the effect of rheology modifiers to the different application methods and finish profile of texture coatings
1.Eudragit is the brand name for a diverse range of polymethacrylate-based copolymers. It includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic/acrylic esters or their derivatives.
2.Applications of different grades of Eudragit in colon-specific/enteric-coated/sustained release drug delivery and taste masking.
3.Eudragits are non-biodegradable, non-absorbable, and nontoxic.
4.Anionic Eudragit L dissolves at pH > 6 and is used for enteric coating, while Eudragit S, soluble at pH > 7 is used for colon targeting. Eudragit RL and RS, having quaternary ammonium groups, are water insoluble, but swellable/permeable polymers which are suitable for the sustained release film coating applications. Cationic Eudragit E, insoluble at pH less than 5, can prevent drug release in saliva and finds application in taste masking.
5.Eudragit is the brand name for a diverse range of copolymers based on polymethacrylates principally marketed by Evonik Industries, Germany. Eudragit was first introduced by Rohm & Hass GmbH, Darmstadt in 1953 as an alkaline soluble drug coating material resistant to stomach acid. It is used for functional pharmaceutical coatings, matrix formers in common granulation techniques as well as in direct compression.
5. Eudragit Nomenclature, Eudragit Abbreviation, Eudragit E, L, S, RL, RS, Cellulose acetate phthalate, HPMC phthalate, HPMC acetate succinate, PVAP
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.
An insight on formulating texture coatings and the effect of rheology modifiers to the different application methods and finish profile of texture coatings
1.Eudragit is the brand name for a diverse range of polymethacrylate-based copolymers. It includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic/acrylic esters or their derivatives.
2.Applications of different grades of Eudragit in colon-specific/enteric-coated/sustained release drug delivery and taste masking.
3.Eudragits are non-biodegradable, non-absorbable, and nontoxic.
4.Anionic Eudragit L dissolves at pH > 6 and is used for enteric coating, while Eudragit S, soluble at pH > 7 is used for colon targeting. Eudragit RL and RS, having quaternary ammonium groups, are water insoluble, but swellable/permeable polymers which are suitable for the sustained release film coating applications. Cationic Eudragit E, insoluble at pH less than 5, can prevent drug release in saliva and finds application in taste masking.
5.Eudragit is the brand name for a diverse range of copolymers based on polymethacrylates principally marketed by Evonik Industries, Germany. Eudragit was first introduced by Rohm & Hass GmbH, Darmstadt in 1953 as an alkaline soluble drug coating material resistant to stomach acid. It is used for functional pharmaceutical coatings, matrix formers in common granulation techniques as well as in direct compression.
5. Eudragit Nomenclature, Eudragit Abbreviation, Eudragit E, L, S, RL, RS, Cellulose acetate phthalate, HPMC phthalate, HPMC acetate succinate, PVAP
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.
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
The festive season is a time for togetherness and celebration. But more importantly, it is a great opportunity to say "Thank You". It is a time to present people with a token of your appreciation to say you're glad for their time, efforts and dedication
HPMC capsule is superior to hard gelatin capsules in terms of mechanical strength, hygroscopicity and compatibility with a
wide range of drugs. It exhibits better short term stability at high temperature conditions and remains flexible even at low moisture content. Two important areas where improvements have to be achieved in order to qualify the HPMC capsules ahead of Gelatin capsules are in their machineability and in the in vitro and in vivo disintegration/dissolution performances.
In Process Quality Control Tests (IPQC) for Solid Dosage FromSagar Savale
IPQC is concerned with providing accurate, specific, & definite descriptions of the procedures to be employed, from, the receipt of raw materials to the release of the finished dosage forms.
DRUG DISSOLUTION, BIO-AVAILABILITY AND IVIVC DEVELOPMENTRoshan Sonkar
Dissolution and drug release tests are in-vitro tests that measure the rate and extent of dissolution or release of the drug substance from a drug product, usually in an aqueous medium under specified conditions.
An overview of Pine Lake Laboratories capabilities involving oligonucleotides. Includes challenges, examples, method development, validation, and stability!
Solubility Enhancement, Stability and Scalability of Mesoporous Silica Formul...MilliporeSigma
In these slides, you will be introduced to the science and scale-up behind mesoporous silica technology, an emerging formulation option for poorly soluble drug delivery.
Included in the slides:
- A broad overview of mesoporous silica technology
- An introduction to the unique stability advantages of mesoporous silica
- Case studies of in vitro and in vivo performance of mesoporous silica formulations
- How to scale-up from lab to production scale
Watch the webinar here: https://bit.ly/2IoV8k7
Similar to HPMC Capsule_USP Workshop_2014 Final (20)
USP Disso Workshop_Tier 2 Method_JHH 11Jun2012 Final v3
HPMC Capsule_USP Workshop_2014 Final
1. Subhead Calibri 14pt, White
Evaluating the Use of
HPMC Capsule in Drug
Product Development
USP Workshop on Dissolution
Testing of Capsules
March 25, 2014
Alex Deac
Kevin Engh
Jian-Hwa Han*
Bill Huang
2. Presentation Outline
• Objective
• Background
• Key Areas of Investigation
• Results and Discussion
- In Vitro Evaluation
- Manufacturability Evaluation
- Brittleness Evaluation
- Cost Consideration
• Conclusion and Recommendation
USP Dissolution Workshop, 2014 2
3. Motivation and Objective
Motivation:
- Limited prior knowledge and experience in using
HPMC capsules for drug product development.
Objective:
- Evaluate physicochemical properties of HPMC capsules
in terms of in-vitro drug release performance and
manufacturability against commonly used Hard Gelatin
Capsule (HGC); identify limitations, if any.
USP Dissolution Workshop, 2014 3
4. Background:
Main Issues of Hard Gelatin Capsules
High moisture content (13-15%)1
• Brittle in low RH (<12% LOD = <30% RH environment)
• Softening in high RH (>18% LOD = > 70% RH environment)
• Risk of using desiccants due to brittleness
Chemical/Physical stability
• Cross-linking over time (high temp, RH, API/excipients/impurities)
Other Concerns for Global Product
• Animal derived ingredient (Collagen)
• BSE/TSE
1. Sherry Ku M., Li, Weiyi. “Performance Qualification of a New Hypromellose Capsule Part I” Capsugel.
USP Dissolution Workshop, 2014 4
5. Background:
HPMC vs. Hard Gelatin Capsules – Pro’s
• Low moisture content (2-7%)
~ 13 % to 65% RH environment
• Less hygroscopic (less sensitive to moisture)
• Plant derived
• No Cross-linking concerns
• Suitable for semi-solid matrix and liquid
formulations
• Better for functional coating (e.g. Enteric coating)
USP Dissolution Workshop, 2014 5
6. Background:
HPMC vs. Hard Gelatin Capsules – Con’s
• Lower film strength at ambient conditions2
• Higher weight variation
• Dissolution issues dependent on the gelling agent used3
• Limited knowledge for in vitro performance, stability,
and manufacturability
• Fewer available vendors
• Risk in switching between vendors due to gelling agents
• Higher unit cost
2. Missaghi, S.,Fassihi, R. “Evaluation and Comparison of Physicomechanical Characteristics of Gelatin and Hypromellose
Capsules”.
3. “Two Piece Gelatine Capsules”. Qualicaps. March, 2013
USP Dissolution Workshop, 2014 6
7. Key Areas of Investigation
• Part I: In vitro performance evaluation
• Part II: Manufacturability evaluation
• Part III: Brittleness evaluation
• Part IV: Cost comparison
USP Dissolution Workshop, 2014 7
8. Part I:
In Vitro Drug Release/Dissolution Experimental
• Materials:
Other HPMC capsules also evaluated on paper: Vcaps (Capsugel), Embo Caps VG (Suheung), NatureCaps
(ACG), K-Caps (Caps Canada)
• Dissolution Media:
– Various pH, Ion types, Ion concentration and surfactants
• Dissolution Method:
– USP II (paddle)
– Continuous FO-UV detection on 6 channels
– 900 ml of media
– 75 rpm ( up to 30 min), 200 rpm (>30 min)
– 37 ºC
– N = 6
– Sinker Type:QLA #CAPWHT-TR
Brand Name Manufacturer Type Gelling Agents Short Name
Coni Snap Capsugel Hard Gelatin none HGC
Vcaps Plus Capsugel HPMC none VC+
Quali-V Qualicap HPMC Carrageenan QV
USP Dissolution Workshop, 2014 8
9. Research Formulation Composition
(for Dissolution Evaluation)
Material Percent
Model compound A (Highly soluble in all
media used)
4.0
Lactose Monohydrate FastFlo #316 57.5
Dibasic Calcium Phosphate, Anhydrous
(FUJICALIN SG)
15.0
Avicel PH-102 15.0
Croscarmellose Sodium 5.0
Hydroxypropyl Cellulose, Vis 10%, 300-600
CPS, Extra Fine
3.0
Magnesium Stearate, (Vegetable Grade) 0.5
USP Dissolution Workshop, 2014 9
11. Dissolution: Surfactant (SDS, POE and CTAB) Effect
Disolution Comparison in Water
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
Time, Min.
%LC
HPMC, VC+ HPMC, QV HGC, Gelatin
Disolution Comparison in 0.5% SDS
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
Time, Min.
%LC
HPMC, VC+ HPMC, QV HGC, Gelatin
Disolution Comparison in 0.5% CTAB
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
Time, Min.
%LC
HPMC, VC+ HPMC, QV HGC, Gelatin
Disolution Comparison in 0.5% POE10LE
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
Time, Min.
%LC
HPMC, VC+ HPMC, QV HGC, Gelatin
Credit to Han, Jian-Hwa H.
QV is
more
sensitive
to CTAB
HGC is
more
sensitive
to SDS
CTAB: Cetyl trimethylammonium bromide; SDS: Sodium dodecyl sulfate; POE: polyoxyethylene lauryl ether
FullRecovery
(@200rpm)
FullRecovery
(@200rpm)
FullRecovery
(@200rpm)
FullRecovery
(@200rpm)
Water SDS
POE CTAB
USP Dissolution Workshop, 2014 11
12. Dissolution: Ionic Effect (Na+ vs. K +)
Disolution Comparison in pH 6.8 Phosphate
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
Time, Min.
%LC
HPMC, VC+ HPMC, QV HGC, Gelatin
Disolution Comparison in pH 6.8 Phosphate (K+)
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
Time, Min.
%LC
HPMC, VC+ HPMC, QV HGC, Gelatin
50 mM Sodium Phosphate 50 mM Potassium Phosphate
Credit to Han, Jian-Hwa H.
Disolution Comparison in Water
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
Time, Min.
%LC
HPMC, VC+ HPMC, QV HGC, Gelatin
In Water as Reference
Slower
opening for
QV
FullRecovery
(@200rpm)
FullRecovery
(@200rpm)
FullRecovery
(@200rpm)
USP Dissolution Workshop, 2014 12
13. Impact of Ion Type and Ion Concentration
on QV Dissolution
Ion Type Effect (@50 mM) “Extreme” Ionic condition
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
%LC
Time, Min.
QV Capsule Dissolution Comparison in 0.01N HCl
Na+ vs. K+ vs. Ca++
50 mM NaCl 50 mM KCl
50 mM CaCl2 0.01N HCl
FullRecovery
(@200rpm)
Na+
K+
Ca++
• 50mM KCl
• 150mM NaCl/110mM KCl/15mM CaCl2
• 300mM NaCl/170mM KCl/30mM CaCl2
USP Dissolution Workshop, 2014 13
14. Effect of Storage Conditions on VC+ Dissolution:
Stability (40ºC/75%RH up to 8 wks)
Capsule 40C/75RH Stability: HPMC VC+ Capsule
(Media = 0.01N HCl)
0.0
20.0
40.0
60.0
80.0
100.0
120.0
0 5 10 15 20 25 30 35 40
Time, Min.
%LC
Initial 1 week 2 weeks 4 weeks 6 weeks 8 weeks
Capsule 40C/75RH Stability: Hard Gelatin Capsule
(Media = 0.01N HCl)
0.0
20.0
40.0
60.0
80.0
100.0
120.0
0 5 10 15 20 25 30 35 40
Time, Min.
%LC
Initial 1 week 2 weeks 4 weeks 6 weeks 8 weeks
VC+ VS. HGC
FullRecovery
(@200rpm)
FullRecovery
(@200rpm)
It is well known that HGC will show slower dissolution profiles when stored
at 40ºC/75%RH conditions.
Some slowing
down, but no
Impact at 30
minutes.
USP Dissolution Workshop, 2014 14
15. Effect of Storage Condition on QV Dissolution
Stability (40ºC/75%RH up to 8 wks)
Capsule 40C/75RH Stability: HPMC QV Capsule
(Media = 0.01N HCl)
0.0
20.0
40.0
60.0
80.0
100.0
120.0
0 5 10 15 20 25 30 35 40
Time, Min.
%LC
Initial 1 week 2 weeks 4 weeks 6 weeks 8 weeks
Capsule 40C/75RH Stability: Hard Gelatin Capsule
(Media = 0.01N HCl)
0.0
20.0
40.0
60.0
80.0
100.0
120.0
0 5 10 15 20 25 30 35 40
Time, Min.
%LC
Initial 1 week 2 weeks 4 weeks 6 weeks 8 weeks
QV vs. HGC
FullRecovery
(@200rpm)
FullRecovery
(@200rpm)
No Impact.
USP Dissolution Workshop, 2014 15
It is well known that HGC will show slower dissolution profiles when stored
at 40ºC/75%RH conditions.
16. 16
Effect of Storage Condition on Dissolution Stability
Under Low RH (~12%) Condition up to 24 Days
0.0
20.0
40.0
60.0
80.0
100.0
120.0
0 5 10 15 20 25 30 35 40
%LC
Time, Min.
Capsule 40C/12RH Stability: Media = 0.01N HCl
VC+ Initial QV Initial HGC Initial
VC+ 24 Days QV 24 Days HGC 24 Days
FullRecovery
(@200rpm)
No difference
after 20 minutes.
USP Dissolution Workshop, 2014
17. Dissolution: Consistency of HGC Across Different Media
Disolution Comparison - Gelatin HGC Capsule
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
Time, Min.
%LC
0.1N HCl pH 4.5 pH 6.8 (Na+) Water
pH 6.8 (K+) SDS CTAB POE
Credit to Han, Jian-Hwa H.
FullRecovery
(@200rpm)
SDS
CTAB
USP Dissolution Workshop, 2014 17
18. Dissolution: Consistency of QV Across Different Media
Disolution Comparison - HPMC QV Capsule
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
Time, Min.
%LC
0.1N HCl pH 4.5 pH 6.8 (Na+) Water
pH 6.8 (K+) SDS CTAB POE
Credit to Han, Jian-Hwa H.
FullRecovery
(@200rpm)
CTAB
K+
USP Dissolution Workshop, 2014 18
19. Dissolution: Consistency of VC+ Across Different Media
Disolution Comparison - HPMC VC+ Capsule
0.0
20.0
40.0
60.0
80.0
100.0
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0
Time, Min.
%LC
0.1N HCl pH 4.5 pH 6.8 (Na+) Water
pH 6.8 (K+) SDS CTAB POE
Credit to Han, Jian-Hwa H.
FullRecovery
(@200rpm)
SDS
USP Dissolution Workshop, 2014 19
20. Case Study 1:
Fast IR Formulation
20
No difference
after 30 minutes.
USP Dissolution Workshop, 2014
21. 21
Case Study 2:
Complicated Formulation - HGC
Potential Spec Point.
FullRecovery
(@200rpm)
USP Dissolution Workshop, 2014
22. 22
Case Study 2:
Complicated Formulation – HPMC/QV
Potential
Spec Point?
FullRecovery
(@200rpm)
USP Dissolution Workshop, 2014
23. 23
Case Study 2:
Complicated Formulation – HPMC/VC+
Potential Spec
Point???
FullRecovery
(@200rpm)
USP Dissolution Workshop, 2014
24. Case Study 2:
Complicated Formulation (Mean Profiles, N=6)
24
Significant Impact to
dissolution results.
USP Dissolution Workshop, 2014
25. Part I: In Vitro Drug Release / Dissolution
Summary
• Longer capsule opening time observed from HPMC capsules.
• With fast releasing formulation, no major dissolution concerns
observed from either HPMC capsule within the normal conditions
tested. However, QV is more sensitive to surfactant (e.g. CTAB) and
Ions, esp. Potassium at higher concentration.
• Both HPMC capsules showed no significant dissolution change
under 40C/75RH open-dish storage.
• No dissolution rate changes observed from storage in low RH for
all capsules (i.e. HGC,QV and VC+).
• For more complicated formulations, thorough evaluation may be
needed before selecting the capsule.
USP Dissolution Workshop, 2014 25
26. Part II: Manufacturability Evaluation
- Capsule Weight Variability
- Robustness of encapsulation under normal
production condition
USP Dissolution Workshop, 2014 26
32. Encapsulation Observations
• No issues regarding rectification, alignment, opening, filling,
closing, and ejecting of either HGC or HPMC capsules during
encapsulation.
• HPMC capsules had a slightly larger weight RSD than HGC.
• Minimal rejects and lot-to-lot variation observed.
• HGC had a shattered capsule in 19% RH conditions. This could
be a potential problem in longer runs. No issues found with
the HPMC capsules.
USP Dissolution Workshop, 2014 32
33. Part II: Manufacturability Evaluation
Summary
- HGC has an overall better empty capsule weight control
than HPMC capsules, however, both QV and VC+ are still
acceptable with the observed variation.
- Both QV and VC+ have demonstrated acceptable
manufacturability/robustness under normal and lower RH
conditions.
- HPMC capsules also demonstrate better physical and
mechanical properties during the encapsulation process as
well as upon storage.
-HGC and HPMC capsules are comparable in terms of
overall manufacturability.
USP Dissolution Workshop, 2014 33
34. Part III: Brittleness Evaluation
Method:
• Capsules were stored in bottles, one per type of capsule
• A set of bottles were stored in desiccators that were
subsequently stored in a chamber with controlled
temperature. A second set of capsules were stored at
ambient conditions in the lab.
• Samples were removed to perform tests under ambient
conditions.
• N=10 capsule per weight drop
USP Dissolution Workshop, 2014 34
35. Brittleness Evaluation – Impact Tester
Equipment Used:
Impact Tester
Hollow tube with a
height of ~2 feet through
which a weight pellet
can be dropped onto a
capsule held in place at
the bottom of the tube
by a capsule holder.
USP Dissolution Workshop, 2014 35
36. 36
Part III: Brittleness Evaluation
Results and Summary
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60
PercentBrokenoutof10
Weight Dropped From 30.25 Inches (g)
Capsule Shell Resistance to Impact at ~22 C° and 35-55% RH
Hard Gelatin
Vcap Plus
Quali-V
0
20
40
60
80
100
0 10 20 30 40 50 60
PercentBrokenoutof10
Weight Dropped From 30.25 Inches (g)
Capsule Shell Resistance to Impact at 40°C and 25% RH for 83 Days
Hard Gelatin
Vcap Plus
Quali-V
HGC becomes more brittle under hi-temp and low humidity condition over
time.
USP Dissolution Workshop, 2014
38. Conclusion and Recommendation
- Both HPMC capsules (i.e. QV and VC+) fit for
Oral Drug Development.
- HPMC capsules are generally not recommended
due to the cost concerns relative to HGC.
- If HPMC capsule will be used, a thorough
evaluation is recommended to make sure the
overall performance meets expectations.
USP Dissolution Workshop, 2014 38
39. • The design, study conduct, and financial support for the
study were provided by Abbvie. Abbvie participated in
the interpretation of data, review, and approval of the
presentation.
• Abbvie is the sole source of funding for the related
studies in this presentation. No other entity has
provided any funding for the related studies in this
presentation.
Disclosures
USP Dissolution Workshop, 2014 39
40. Acknowledgement
• Dr. Jian-Hwa Han is employed at Abbvie. Dr. Han planned and
executed the dissolution experiments for this study.
• Dr. Ye Huang is employed at Abbvie. Dr. Huang was the primary
investigator for this study.
• Mr. Alexandru Deac is employed at Abbvie. Mr. Deac was the key
formulator for this study.
• Mr. Kevin Engh is employed at Abbvie. Mr. Engh was the process
engineer for this study.
• Dr. Gregory K. Webster and Dr. Paul D. Curry, Jr. are employed at
Abbvie who contributed to scientific discussions and reviewed the
presentation materials.
40USP Dissolution Workshop, 2014