This document provides an overview of a presentation on using enzymes for dissolution testing. It discusses gelatin dissolution in various media, using acetaminophen as a reference compound to compare tablet and over-encapsulated tablet dissolution. It also evaluates the performance of enzymes like pepsin, bromelain and papain compared to the USP standard of pepsin. Cross-linked over-encapsulated samples showed slower dissolution than non-cross-linked capsules. While enzymes performed equivalently to pepsin for non-cross-linked capsules, they failed to dissolve cross-linked capsules within USP specifications. The presentation aims to establish reference points and evaluate the reproducibility of different enzymes.
This presentation discusses dissolution testing methods for cross-linked gelatin capsules. It begins with an overview of gelatin dissolution properties and how surfactants can impact dissolution rates. Acetaminophen capsule and tablet dissolution results are then compared in various media. The presentation explores using tier-2 dissolution testing methods from USP <711> for cross-linked capsules, evaluating pepsin and pancreatin enzyme levels. It concludes by proposing the use of bromelain and papain enzymes for evaluating dissolution at pH 4.5.
The document discusses developing dissolution methods that provide discriminating power between drug products. It emphasizes starting with an understanding of the active pharmaceutical ingredient properties and dosage form. Critical elements for dissolution methods include being predictive, reproducible and transferring between labs. Sources of variability must be minimized through controls. Methods can be made more discriminating by selection of apparatus, conditions and relevant sample types. The goal is a method tailored to the intended use and product characteristics that maintains consistent performance for quality assurance.
USP Disso Workshop_Tier 2 Method_JHH 11Jun2012 Final v3Jian-Hwa Han 韓建華
The document discusses tier-2 dissolution testing methods for cross-linked gelatin capsules from an analytical lab perspective. It describes common causes of gelatin cross-linking including aldehydes, temperature, humidity, and UV light. It also analyzes the effectiveness of pepsin versus pancreatin enzymes in dissolution media based on their pH activity curves. Finally, it proposes a two-step tier-2 method for poorly soluble drugs using surfactant media to improve the test.
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.
This document provides an overview of a webinar on sample preparation techniques for pesticide residue analysis, focusing on QuEChERS extraction. It discusses the challenges of pesticide residue analysis in complex food matrices and how QuEChERS extraction addresses these challenges through a simple, fast, and cost-effective process. The document reviews different QuEChERS extraction methods and provides tips on selecting the appropriate method based on analytes of interest and matrix type. It also discusses troubleshooting poor recoveries and provides examples of pesticide residue analysis in different food matrices using QuEChERS extraction.
This document contains standard operating procedures for analyzing moisture content, crude protein content, and protein preparation methods at PT. New Hope Jawa Timur. The moisture content method involves drying a 5g sample at 130°C for 2 hours and calculating moisture percentage based on weight loss. The crude protein Kjeldahl method involves digestion, distillation, and titration to determine nitrogen content and calculate crude protein. Reagents, equipment, and steps are outlined for each analytical method.
For HPLC, sample solvents that adequately dissolve target compounds are required. Therefore, sample solvents that contain a high concentration of organic solvent are often used for reversed phase chromatography. The problem is that these solvents sometimes cause peak broadening.
This presentation discusses techniques for reducing the effects of sample solvents on UHPLC analyses.
This presentation discusses dissolution testing methods for cross-linked gelatin capsules. It begins with an overview of gelatin dissolution properties and how surfactants can impact dissolution rates. Acetaminophen capsule and tablet dissolution results are then compared in various media. The presentation explores using tier-2 dissolution testing methods from USP <711> for cross-linked capsules, evaluating pepsin and pancreatin enzyme levels. It concludes by proposing the use of bromelain and papain enzymes for evaluating dissolution at pH 4.5.
The document discusses developing dissolution methods that provide discriminating power between drug products. It emphasizes starting with an understanding of the active pharmaceutical ingredient properties and dosage form. Critical elements for dissolution methods include being predictive, reproducible and transferring between labs. Sources of variability must be minimized through controls. Methods can be made more discriminating by selection of apparatus, conditions and relevant sample types. The goal is a method tailored to the intended use and product characteristics that maintains consistent performance for quality assurance.
USP Disso Workshop_Tier 2 Method_JHH 11Jun2012 Final v3Jian-Hwa Han 韓建華
The document discusses tier-2 dissolution testing methods for cross-linked gelatin capsules from an analytical lab perspective. It describes common causes of gelatin cross-linking including aldehydes, temperature, humidity, and UV light. It also analyzes the effectiveness of pepsin versus pancreatin enzymes in dissolution media based on their pH activity curves. Finally, it proposes a two-step tier-2 method for poorly soluble drugs using surfactant media to improve the test.
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.
This document provides an overview of a webinar on sample preparation techniques for pesticide residue analysis, focusing on QuEChERS extraction. It discusses the challenges of pesticide residue analysis in complex food matrices and how QuEChERS extraction addresses these challenges through a simple, fast, and cost-effective process. The document reviews different QuEChERS extraction methods and provides tips on selecting the appropriate method based on analytes of interest and matrix type. It also discusses troubleshooting poor recoveries and provides examples of pesticide residue analysis in different food matrices using QuEChERS extraction.
This document contains standard operating procedures for analyzing moisture content, crude protein content, and protein preparation methods at PT. New Hope Jawa Timur. The moisture content method involves drying a 5g sample at 130°C for 2 hours and calculating moisture percentage based on weight loss. The crude protein Kjeldahl method involves digestion, distillation, and titration to determine nitrogen content and calculate crude protein. Reagents, equipment, and steps are outlined for each analytical method.
For HPLC, sample solvents that adequately dissolve target compounds are required. Therefore, sample solvents that contain a high concentration of organic solvent are often used for reversed phase chromatography. The problem is that these solvents sometimes cause peak broadening.
This presentation discusses techniques for reducing the effects of sample solvents on UHPLC analyses.
The automation of sample preparation has become an increasingly important component for reproducible and operator-independent experiments. This work outlines novel strategies that are being utilized for automated online and offline sample preparation to achieve specific goals, such as a host of applications including targeting post-translationally modified proteins, non-tryptic peptides, and intact proteins.
NOVEL IPQCL AND FPQC TEST FOR OPTHALMIC PREPARATION AS PER IP, BP A...roshan telrandhe
Ophthalmic preparation are the sterile liquid or semisolid preparation meant to installation in to the eyes in the space between eye lids and eye ball .
These product must be sterile and are prepare under the same condition as that of parenteral preparation
This document describes a study to isolate and screen methyl parathion degrading Aspergilli from soil. The key objectives were to:
1) Isolate and screen Aspergillus fungi that produce methyl parathion hydrolase (MPH), an enzyme that breaks down methyl parathion.
2) Compare the methyl parathion degradation potential of 7 Aspergillus niger isolates.
3) Quantify MPH production by determining enzyme activity levels.
Various soils were used to isolate fungi, which were screened on media containing methyl parathion. The most promising isolates were tested in broth for their ability to degrade methyl parathion at different concentrations, with
The document summarizes research on the application and performance of glyphosate in Turkey. It describes how glyphosate is commonly used in perennial crops and non-agricultural areas in Turkey. It then discusses experiments conducted to investigate reasons for glyphosate reportedly failing to control certain weed species. The experiments varied glyphosate formulation, dose, spray water volume and quality, weed growth stage, and climatic conditions during application. The results showed that increasing spray water volume and controlling weeds at earlier growth stages improved glyphosate efficacy. Water quality and formulation also impacted effectiveness against different weed species.
This document describes a behavioral toxicity test method using the ciliated protozoan Tetrahymena thermophila. The test measures the chemotactic response of T. thermophila to toxic chemicals by observing their movement in a T-maze apparatus with one arm containing the test chemical and the other containing a control solution. Tests using sodium chloride and guaiacol reference toxicants yielded reproducible results, indicating the method has potential for reliably testing industrial effluents. The document provides details on culturing T. thermophila, conducting motility and exposure tests in the T-maze apparatus over 20 minutes, and enumerating cells to determine chemotactic response.
Oxygen Demand, Chemical with chloride removal 10067 (Manganese III Reactor Digestion Method) measures COD in water and wastewater samples from 30 to 1000 mg/L. The test uses a vacuum pretreatment to remove chloride interference followed by a digestion with manganese III reagent and measurement at 510 nm. Accuracy is ensured through calibration with potassium acid phthalate and an optional standard check with an 800 mg/L COD standard solution.
Determination of Insoluble Solids in Pretreated BiomassBiorefineryEPC™
Determination of Insoluble Solids in Pretreated Biomass
DISCLAIMER:
YOU AGREE TO INDEMNIFY BioRefineryEPC™ , AND ITS AFFILIATES, OFFICERS, AGENTS, AND EMPLOYEES AGAINST ANY CLAIM OR DEMAND, INCLUDING REASONABLE ATTORNEYS' FEES, RELATED TO YOUR USE, RELIANCE, OR ADOPTION OF THE DATA FOR ANY PURPOSE WHATSOEVER. THE DATA ARE PROVIDED BY BioRefineryEPC™ "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING BUT NOT LIMITED TO THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE EXPRESSLY DISCLAIMED. IN NO EVENT SHALL BioRefineryEPC™ BE LIABLE FOR ANY SPECIAL, INDIRECT OR CONSEQUENTIAL DAMAGES OR ANY DAMAGES WHATSOEVER, INCLUDING BUT NOT LIMITED TO CLAIMS ASSOCIATED WITH THE LOSS OF DATA OR PROFITS, WHICH MAY RESULT FROM ANY ACTION IN CONTRACT, NEGLIGENCE OR OTHER TORTIOUS CLAIM THAT ARISES OUT OF OR IN CONNECTION WITH THE USE OR PERFORMANCE OF THE DATA.
The document discusses cybersecurity statistics that highlight the threats companies face from cyber attacks and data breaches. It notes that there were over 1.5 million cyber attacks in the US in 2013, companies face an average of 16,800 attacks per year, and email remains the most common method of attack, putting 75% of companies at high risk. The statistics are intended to motivate companies to protect themselves using a multi-layered security approach.
This document summarizes the findings of a study on marketing ROI and data usage among large corporate marketers. Some key findings include:
1) While 91% of marketers believe successful brands use customer data to drive decisions, many are not collecting the right types of data like mobile or social media data as frequently as traditional demographic data.
2) Marketers have adopted many new digital marketing tools but struggle to measure their effectiveness, with only 14% tying social media marketing and 17% tying mobile ads to financial metrics.
3) Comparing the effectiveness of different digital marketing channels is a major challenge for 60% of companies due to different engagement metrics used for each channel.
4) Over half of market
This document summarizes the ROM persistence toolkit for Ruby. It provides a concise and leaky abstraction for managing data access with relations, commands and repositories. Key concepts include configuration, relations, pipelines and commands. Relations provide a clean separation between data and query logic. Pipelines allow chaining operations. Commands standardize CRUD operations. It aims to reduce global state and promote object composition with a mix of functional and object-oriented patterns.
Toolkit for supporting social innovation with the ESIFESF Vlaanderen
This document provides a toolkit for European Structural and Investment Funds (ESIF) programme managers to support social innovation. It begins with an overview of how social innovation is addressed in EU policies and defines key concepts. It then covers theories relevant to social innovation such as capabilities approach, service innovation, transition theory and changemaker theory. It provides guidance on developing an innovation strategy for ESIF programmes and supporting the innovation process and capacities required at project level. It includes practical tools, cases and an implementation plan to help ESIF managers operationalize social innovation.
This document lists the cubes of integers from 1 to 10. It provides the step-by-step work of calculating each cube, such as 1 x 1 x 1 = 1, 2 x 2 x 2 = 8, and so on up to 10 x 10 x 10 = 1000. It notes that these numbers are also called cubic numbers.
Dokumen ini membahas tentang pengaturan font, memformat paragraf, dan mengelola gambar serta ilustrasi di Microsoft Word. Microsoft Word sering digunakan untuk mengetik dan membuat berbagai jenis dokumen seperti surat, laporan, soal, dan lainnya.
Castro Village Bowl is a bowling alley located in Castro Valley, California that has been in business since 1961. While it has a loyal customer base and offers affordable prices and frequent promotions, it is missing out on attracting younger customers. Research methods including surveys, interviews, and analyzing social media and review sites found that the bowling alley lacks a strong social media presence and many of its events are geared toward older patrons. A proposed strategic plan includes partnering with the local high school on youth-focused events, updating the alley's appearance, and growing its social media presence in order to attract more young customers and their families.
Golden Tree Jewellers is an Authorized Dealer of the biggest luxury brands in engagement ring and watches. We Serve: Vancouver, Burnaby, Surrey, Langley and B.C.
http://www.goldentreejewellers.com/
William Shakespeare was an English playwright and poet born in 1564 in Stratford-upon-Avon, Warwickshire. He is widely considered one of the greatest writers in the English language and produced most of his plays between 1589-1613, including famous tragedies like Hamlet, Romeo and Juliet, Othello, and Macbeth. Shakespeare died in 1616 in Stratford-upon-Avon at the age of 52.
Los sistemas transaccionales se enfocan en recolectar y almacenar datos operacionales para automatizar tareas y ahorrar costos, mientras que los sistemas estratégicos procesan información para optimizar procesos, incrementar ventajas competitivas y contribuir a los objetivos estratégicos de la empresa mediante la innovación. Mientras los sistemas transaccionales ofrecen datos cuantificados y visibles para lograr objetivos operativos, los sistemas estratégicos evalúan estrategias para generar ahorros y cambios signific
The automation of sample preparation has become an increasingly important component for reproducible and operator-independent experiments. This work outlines novel strategies that are being utilized for automated online and offline sample preparation to achieve specific goals, such as a host of applications including targeting post-translationally modified proteins, non-tryptic peptides, and intact proteins.
NOVEL IPQCL AND FPQC TEST FOR OPTHALMIC PREPARATION AS PER IP, BP A...roshan telrandhe
Ophthalmic preparation are the sterile liquid or semisolid preparation meant to installation in to the eyes in the space between eye lids and eye ball .
These product must be sterile and are prepare under the same condition as that of parenteral preparation
This document describes a study to isolate and screen methyl parathion degrading Aspergilli from soil. The key objectives were to:
1) Isolate and screen Aspergillus fungi that produce methyl parathion hydrolase (MPH), an enzyme that breaks down methyl parathion.
2) Compare the methyl parathion degradation potential of 7 Aspergillus niger isolates.
3) Quantify MPH production by determining enzyme activity levels.
Various soils were used to isolate fungi, which were screened on media containing methyl parathion. The most promising isolates were tested in broth for their ability to degrade methyl parathion at different concentrations, with
The document summarizes research on the application and performance of glyphosate in Turkey. It describes how glyphosate is commonly used in perennial crops and non-agricultural areas in Turkey. It then discusses experiments conducted to investigate reasons for glyphosate reportedly failing to control certain weed species. The experiments varied glyphosate formulation, dose, spray water volume and quality, weed growth stage, and climatic conditions during application. The results showed that increasing spray water volume and controlling weeds at earlier growth stages improved glyphosate efficacy. Water quality and formulation also impacted effectiveness against different weed species.
This document describes a behavioral toxicity test method using the ciliated protozoan Tetrahymena thermophila. The test measures the chemotactic response of T. thermophila to toxic chemicals by observing their movement in a T-maze apparatus with one arm containing the test chemical and the other containing a control solution. Tests using sodium chloride and guaiacol reference toxicants yielded reproducible results, indicating the method has potential for reliably testing industrial effluents. The document provides details on culturing T. thermophila, conducting motility and exposure tests in the T-maze apparatus over 20 minutes, and enumerating cells to determine chemotactic response.
Oxygen Demand, Chemical with chloride removal 10067 (Manganese III Reactor Digestion Method) measures COD in water and wastewater samples from 30 to 1000 mg/L. The test uses a vacuum pretreatment to remove chloride interference followed by a digestion with manganese III reagent and measurement at 510 nm. Accuracy is ensured through calibration with potassium acid phthalate and an optional standard check with an 800 mg/L COD standard solution.
Determination of Insoluble Solids in Pretreated BiomassBiorefineryEPC™
Determination of Insoluble Solids in Pretreated Biomass
DISCLAIMER:
YOU AGREE TO INDEMNIFY BioRefineryEPC™ , AND ITS AFFILIATES, OFFICERS, AGENTS, AND EMPLOYEES AGAINST ANY CLAIM OR DEMAND, INCLUDING REASONABLE ATTORNEYS' FEES, RELATED TO YOUR USE, RELIANCE, OR ADOPTION OF THE DATA FOR ANY PURPOSE WHATSOEVER. THE DATA ARE PROVIDED BY BioRefineryEPC™ "AS IS" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING BUT NOT LIMITED TO THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE EXPRESSLY DISCLAIMED. IN NO EVENT SHALL BioRefineryEPC™ BE LIABLE FOR ANY SPECIAL, INDIRECT OR CONSEQUENTIAL DAMAGES OR ANY DAMAGES WHATSOEVER, INCLUDING BUT NOT LIMITED TO CLAIMS ASSOCIATED WITH THE LOSS OF DATA OR PROFITS, WHICH MAY RESULT FROM ANY ACTION IN CONTRACT, NEGLIGENCE OR OTHER TORTIOUS CLAIM THAT ARISES OUT OF OR IN CONNECTION WITH THE USE OR PERFORMANCE OF THE DATA.
The document discusses cybersecurity statistics that highlight the threats companies face from cyber attacks and data breaches. It notes that there were over 1.5 million cyber attacks in the US in 2013, companies face an average of 16,800 attacks per year, and email remains the most common method of attack, putting 75% of companies at high risk. The statistics are intended to motivate companies to protect themselves using a multi-layered security approach.
This document summarizes the findings of a study on marketing ROI and data usage among large corporate marketers. Some key findings include:
1) While 91% of marketers believe successful brands use customer data to drive decisions, many are not collecting the right types of data like mobile or social media data as frequently as traditional demographic data.
2) Marketers have adopted many new digital marketing tools but struggle to measure their effectiveness, with only 14% tying social media marketing and 17% tying mobile ads to financial metrics.
3) Comparing the effectiveness of different digital marketing channels is a major challenge for 60% of companies due to different engagement metrics used for each channel.
4) Over half of market
This document summarizes the ROM persistence toolkit for Ruby. It provides a concise and leaky abstraction for managing data access with relations, commands and repositories. Key concepts include configuration, relations, pipelines and commands. Relations provide a clean separation between data and query logic. Pipelines allow chaining operations. Commands standardize CRUD operations. It aims to reduce global state and promote object composition with a mix of functional and object-oriented patterns.
Toolkit for supporting social innovation with the ESIFESF Vlaanderen
This document provides a toolkit for European Structural and Investment Funds (ESIF) programme managers to support social innovation. It begins with an overview of how social innovation is addressed in EU policies and defines key concepts. It then covers theories relevant to social innovation such as capabilities approach, service innovation, transition theory and changemaker theory. It provides guidance on developing an innovation strategy for ESIF programmes and supporting the innovation process and capacities required at project level. It includes practical tools, cases and an implementation plan to help ESIF managers operationalize social innovation.
This document lists the cubes of integers from 1 to 10. It provides the step-by-step work of calculating each cube, such as 1 x 1 x 1 = 1, 2 x 2 x 2 = 8, and so on up to 10 x 10 x 10 = 1000. It notes that these numbers are also called cubic numbers.
Dokumen ini membahas tentang pengaturan font, memformat paragraf, dan mengelola gambar serta ilustrasi di Microsoft Word. Microsoft Word sering digunakan untuk mengetik dan membuat berbagai jenis dokumen seperti surat, laporan, soal, dan lainnya.
Castro Village Bowl is a bowling alley located in Castro Valley, California that has been in business since 1961. While it has a loyal customer base and offers affordable prices and frequent promotions, it is missing out on attracting younger customers. Research methods including surveys, interviews, and analyzing social media and review sites found that the bowling alley lacks a strong social media presence and many of its events are geared toward older patrons. A proposed strategic plan includes partnering with the local high school on youth-focused events, updating the alley's appearance, and growing its social media presence in order to attract more young customers and their families.
Golden Tree Jewellers is an Authorized Dealer of the biggest luxury brands in engagement ring and watches. We Serve: Vancouver, Burnaby, Surrey, Langley and B.C.
http://www.goldentreejewellers.com/
William Shakespeare was an English playwright and poet born in 1564 in Stratford-upon-Avon, Warwickshire. He is widely considered one of the greatest writers in the English language and produced most of his plays between 1589-1613, including famous tragedies like Hamlet, Romeo and Juliet, Othello, and Macbeth. Shakespeare died in 1616 in Stratford-upon-Avon at the age of 52.
Los sistemas transaccionales se enfocan en recolectar y almacenar datos operacionales para automatizar tareas y ahorrar costos, mientras que los sistemas estratégicos procesan información para optimizar procesos, incrementar ventajas competitivas y contribuir a los objetivos estratégicos de la empresa mediante la innovación. Mientras los sistemas transaccionales ofrecen datos cuantificados y visibles para lograr objetivos operativos, los sistemas estratégicos evalúan estrategias para generar ahorros y cambios signific
El documento presenta el calendario de la competición de la Liga Asolefusa 1a División Provincial, con 15 jornadas programadas entre octubre de 2015 y febrero de 2016. En cada jornada se enfrentan 8 equipos los sábados en diferentes campos.
This document defines and describes various cinematography techniques:
- A birds eye view shot photographs a scene from directly overhead.
- A crane shot is taken from a mechanical arm that can move the camera in any direction.
- Cross cutting alternates shots from two sequences to suggest they are happening simultaneously.
- An establishing shot provides context at the beginning of a scene from an extreme long or long shot.
- An extreme close up shows a minutely detailed view of an object or person's eyes or mouth.
- An extreme long shot photographs an exterior location from a great distance, up to a quarter mile away.
This document provides an overview of the TRANSIT research project which studies transformative social innovation. The project involves 20 social innovation networks across Europe and Latin America. It uses a multi-level perspective to understand how social innovation initiatives contribute to sustainability transitions. Preliminary insights include how narratives of change and "game-changers" influence social innovation, the renewal of social relations through new values, and challenges to existing institutions. The summary concludes with 5 preliminary policy insights around acknowledging changing social relations, allowing institutional hybridity, qualitative monitoring of impact, supporting translocal networks, and long-term systemic support.
Mohammah Ahmed Bahafzalla has over 8 years of experience in middle management roles such as procurement supervisor, process engineer, and acting superintendent. He has a proven track record of improving performance in production, technical, and management. He currently works as an aircraft maintenance planner at SAEI in Jeddah, Saudi Arabia, where he coordinates maintenance schedules and ensures aircraft restrictions are addressed.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms for those who already suffer from conditions like anxiety and depression.
In Process Quality Control Tests (IPQC) for Solid Dosage FromSagar Savale
This document discusses in-process quality control tests that are performed during the manufacturing of solid oral dosage forms such as tablets and capsules. It provides details about common tests like weight variation, hardness, friability, disintegration and dissolution. The tests help to identify any issues during production so that corrective actions can be taken. Specific test methods, acceptance criteria and instruments used for tests are outlined for various types of oral dosage forms including immediate release tablets, sustained release tablets, capsules and suppositories. Maintaining quality during manufacturing is important to deliver consistent drug levels in patients.
Dissolution procedure development and validation, USP 1092Md. Saddam Nawaz
This document discusses the development and validation of dissolution procedures according to USP<1092>. It provides general comments on the purpose of dissolution testing and discusses key aspects of developing a discriminating and reproducible method, including choice of medium, apparatus, study design, sampling, and validation. The document outlines factors to consider for various dosage forms and provides examples of typical dissolution conditions and acceptance criteria.
Accurex Biomedical Pvt. Ltd. is an Indian manufacturer and marketer which provides accurate and quality solutions in the diagnostic industry. We have been in this business for over 38 years and are currently one of the top 3 Indian companies in the field of Clinical chemistry, known for high quality of products.
Our company name is composed of two words, ACCU and REX. ‘ACCU’ refers to the word ‘accurate’. Its definition as described by Oxford dictionary portrays the essence of our existence. ‘REX’, a Latin word for ‘king’, speaks of our authoritative influence in the diagnostic industry.
Guided by clear vision and driven by innovation; Accurex has gained considerable expertise in manufacturing and marketing of In-vitro Diagnostic reagents. It has built a reputation of quality products, a strong financial base and dynamic marketing.
Accurex is a leader in the In-vitro Diagnostic segment in India, with world-class products and solutions in all segments - Clinical Chemistry, Critical Care, Diabetes Management, Haematology, Immunology, Microbiology, Molecular and Urinalysis.
Over 3 decades, Accurex believes in providing Accuracy, best quality and affordable prices. We believe that quality healthcare should be available for all. Accurex is striving for the best in products and service.
This document provides information on the formulation and evaluation of gastroretentive floating tablets of Cefadroxil using natural polymers. The objectives were to prepare floating tablets using polymers to achieve sustained release, optimize polymer concentrations, and evaluate tablet properties. Cefadroxil was selected as the model drug based on its absorption window and stability in gastric pH. Xanthan gum and guar gum were chosen as natural polymers based on their matrix-forming abilities and floating properties. Tablets were prepared by direct compression using various polymer concentrations and evaluated for properties like hardness, friability, swelling index and in vitro drug release. The results showed that the formulations using natural polymers were able to float and release the drug in a sustained manner
The document summarizes research comparing the disinfection of wastewater using peracetic acid (PAA) and sodium hypochlorite. It discusses two case studies - jar testing of PAA and sodium hypochlorite at a wastewater facility in Cincinnati, and a study comparing the two disinfectants at a combined sewer overflow facility in Steubenville, Ohio. The research found that PAA was generally as effective as sodium hypochlorite at inactivating bacteria, but required a higher dose. PAA also produced fewer harmful byproducts and had lower aquatic toxicity than sodium hypochlorite. An ongoing study is evaluating the two disinfectants further at a CSO facility in
This document outlines the validation of an analytical method for quantifying gentamycin sulfate in gentamycin sulfate cream using a microbial assay. The method involves extracting gentamycin sulfate from cream samples using chloroform, then performing a cylinder plate assay with Staphylococcus epidermidis to quantify gentamycin sulfate levels. The validation will evaluate the method's specificity, precision, intermediate precision (ruggedness), and accuracy according to ICH guidelines. Responsibilities for developing and approving the validation protocol and performing testing are defined. The validation protocol describes the product profile, materials and equipment needed, analytical method, and performance parameters to be tested.
The document discusses developing a chronotherapeutic drug delivery system for salbutamol sulphate to treat asthma. It aims to release the drug in a pulsatile manner at specific times corresponding to the pathophysiological needs of asthma. The objectives are to study the preformulation parameters of salbutamol sulphate and develop immediate and extended release formulations using tablet in capsule technology to achieve pulse release during midnights or early mornings. The methodology involves characterizing the drug and excipients, developing IR and ER tablet formulations, and evaluating them for micromeritic properties, drug release, and stability.
IPQC tests are important quality control checks performed during the manufacturing of tablets, capsules, and ointments. For tablets, key tests include weight variation, disintegration, dissolution, drug content, hardness, and friability. Tests for capsules include uniformity of content, disintegration, weight variation, and dissolution. Common tests for ointments are not described. IPQC aims to detect errors, minimize human error, and ensure quality at each stage of production according to established procedures.
Formulation and Evaluation of immediate release tablet in treatment of overac...BhuminJain1
Overactive bladder (OAB) is a combination of urinary symptoms that includes a sudden, strong need to urinate. The major symptom of OAB is a sudden, strong urge to urinate that you can't ignore. Leak urine or have “urge incontinence.” This means urine leaks when you feel the sudden urge to go.
Urinate frequently. You may need to go to the bathroom many times during the day.
Wake up at night to pass urine.
The cost for (branded) oral tablet 10 mg is around $411 for a supply of 30 tablets. It indicates that there is strong need of generic version for affordable healthcare.
The data shows that number of people affected with overactive bladder is 37 million.
This document provides an overview of dissolution specifications. It discusses the purpose of specifications in ensuring drug product quality and consistency. It reviews specifications for different dosage forms like immediate-release, extended-release, and delayed-release as outlined in USP <711>. The presentation discusses factors to consider in justifying specifications scientifically, including drug properties, formulation, manufacturing processes, and clinical data. It provides an example of using an IVIVC model to help establish clinically relevant dissolution methods and specifications.
Stability indicating rp hplc method development and validation for simultaneo...Rajasekhar
The document describes the development and validation of a stability-indicating RP-HPLC method for the simultaneous estimation of levodropropizine and chlorpheniramine maleate in bulk and pharmaceutical dosage forms. The method utilizes a C18 column with a mobile phase of 45% 0.1% orthophosphoric acid and 55% acetonitrile at a flow rate of 1 mL/min. The method was validated for parameters such as linearity, accuracy, precision, specificity, limit of detection, limit of quantification and robustness according to ICH guidelines. Forced degradation studies were also performed to demonstrate the stability-indicating ability of the developed method.
Preparation of large volume and small volume parenteralsangram maskar
Large volume parenterals are sterile aqueous drug products packaged in single-dose containers holding 100 mL or more. Small volume parenterals are packaged in containers holding 100 mL or less. Both are administered via intravenous, intramuscular, or subcutaneous routes. Key differences include that small volume parenterals may use preservatives and not require isotonicity, while large volume parenterals must be isotonic. Both undergo processes like cleaning, preparation, sterilization, filling, and packaging to ensure sterility. They are tested using methods like sterility testing, particulate testing, and pyrogen testing to ensure quality and safety.
This poster is an overview of the four main projects I worked on at my summer at Streck. This board was created as a summary for a all-employee showcase.
Comprehensive Investigation of the Utilization of SFC/ESI Positive Mode MS fo...Waters Corporation
This document discusses the use of single column convergence chromatography/mass spectrometry (UPC2/MS) for bioanalytical studies. It provides examples of how UPC2/MS can simplify workflows by reducing sample preparation times through direct injection of extracts and improving selectivity over reversed phase chromatography. UPC2/MS also allows for faster separation of challenging compound classes like isomers and lipids compared to traditional techniques like gas chromatography. The document concludes that UPC2/MS provides an orthogonal separation method and combines multiple techniques into one analytical platform for streamlining quantitative bioanalysis in drug discovery and development.
Presented at INTERPHEX on March 21-23, 2017.
This presentation is an overview of various techniques for performing extractable studies, including protocols of several organizations. It goes into detail in comparing USP requirements to BPOG requirements, showing that in the end, patient safety is demonstrated with limited model solvents and time points.
Biopharmaceutics and Pharmacokinetics Practical ManualReshma Fathima .K
The document describes an experiment to determine the partition coefficient and dissociation constant of ibuprofen. It provides background on how these properties influence drug absorption. The pH-partition hypothesis states that passive drug diffusion is governed by the drug's pKa, lipid solubility of the un-ionized form (partition coefficient), and gastrointestinal pH. The experiment involves measuring the extraction of ibuprofen into an organic phase at different buffer pH levels to calculate the apparent and true partition coefficients and dissociation constant. Plotting the results allows determining these pharmacokinetic parameters.
Dissolution is a test used to evaluate the rate of release of a drug substance from a dosage form. It assesses the performance of drug products and aims to be predictive of bioavailability. The first dissolution studies were reported in 1897 and focused on relating dissolution to drug absorption. Key factors that can affect dissolution include the apparatus used, temperature, media composition and pH, as well as formulation aspects like excipients. Proper procedure involves setting standardized conditions for the apparatus, media preparation, running the test, and calculating the percentage of drug dissolved within a specified time period.
This document outlines standard operating procedures for pH testing of products produced in China for Gap Inc. brands. It details the responsibilities of various parties in the testing process including garment factories, laundries, Gap QA teams, and local labs. Key points covered include the pH testing process flow, required equipment and methods, responsibilities of different stakeholders, and differences between Gap protocols and China's national standards. The overarching goal is to ensure all China-produced products meet Gap's published pH standards regardless of brand or product type.
1. Jian-Hwa Han
USP Expert Panel Meeting
May 29-30, 2013
Using Enzymes for
Dissolution - The
Understandings from
Gelatin to Enzymes
SUB-TITLE, DATE
2. • Dissolution Equipment and Apparatus
• Gelatin Dissolution in Various Media
• Reference Compound – Acetaminophen
o Tablet vs. OE Capsule (Over-encapsulated Tablet sample)
• Tier-2 Testing Performance Evaluation
o Enzymes Information
o Control of Experiments
o Setting the Reference Point - <711> Pepsin
o Equivalent Performance of other Enzymes
o Reproducibility of Bromelain and Papain
o Disintegration Evaluation
• Summary & Next Step
Presentation Outline
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
2
3. Dissolution by FO-UV System
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
3
• System 1: Distek Opt-Diss FO-UV Dissolution System
• System 2: Sotax with Rainbow FO-UV System
• Advantage: Direct detection with details profiles
(and w/o Sampling errors)
• Apparatus 2 @ 50 rpm
• Samples
• Hard Gelatin Shell
• Tylenol Tablet
• OE Tylenol Sample
• Cross-linked OE Tylenol Sample
5. Gelatin Dissolution – Typical Media
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
5
• Data clearly
show much
faster
dissolution rate
in 0.1N HCl
• The dissolution
rates in pH 4.5,
pH 6.8, and
water are
similar
Dissolution of Hard Gelatin Shell - App 2 @ 50 rpm
in Typical Dissolution Media
0.0
20.0
40.0
60.0
80.0
100.0
120.0
0.0 10.0 20.0 30.0 40.0 50.0 60.0
Time, Minutes
%LC
0.1N HCl Acetate, pH 4.5 Phosphate, pH 6.8 Water
6. Gelatin Dissolution –
Surfactant Impact in Water
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
6
• Surfactants do
slow down the
dissolution of
gelatin
• The impact
from POE and
CTAB are not
significant
• SDS posts more
impact, but it
still within the
variability
Dissolution of Hard Gelatin Shell - App 2 @ 50 rpm
Surfactant Impact in Water
0.0
20.0
40.0
60.0
80.0
100.0
120.0
0.0 10.0 20.0 30.0 40.0 50.0 60.0
Time, Minutes
%LC
Water 0.5% SDS in Water 0.5% POE in Water 0.2% CTAB in Water
7. Gelatin Dissolution –
Surfactant Impact in pH 6.8 Phosphate Media
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
7
• No significant
impact
observed in
pH 6.8
Phosphate
media with
either SDS or
POE10LE
Dissolution of Hard Gelatin Shell - App 2 @ 50 rpm
Surfactant Impact in pH 6.8 Phophaste Buffer
0.0
20.0
40.0
60.0
80.0
100.0
120.0
0.0 10.0 20.0 30.0 40.0 50.0 60.0
Time, Minutes
%LC
0.5% SDS in pH 6.8 pH 6.8 Buffer 0.5% POE in pH 6.8
8. Gelatin Dissolution –
Surfactant Impact in 0.1N HCl Media
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
8
• No significant
impact
observed for
POE in
0.1N HCl media
• Significant
impact
observed for
SDS in 0.1N HCl
media!!!
Dissolution of Hard Gelatin Shell - App 2 @ 50 rpm
Surfactant Impact in 0.1N HCl
0.0
20.0
40.0
60.0
80.0
100.0
120.0
0.0 10.0 20.0 30.0 40.0 50.0 60.0
Time, Minutes
%LC
0.5% SDS in HCl 0.1N HCl 0.5% POE in HCl
9. Comparison of Gelatin Dissolution Time in
Various Media
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
9
Note – In general, the capsule opens within 2 minutes in 0.1N HCl.
Gelatin Dissolution Comparison
0
5
10
15
20
25
30
0.1
N
HC
l,900
m
L
0.5%
SDS/0.1N
H
C
l
0.5%
PO
E/0.1N
H
Cl
Phosphate,pH
6.8
0.5%
SDS/pH
6.8
0.5%
PO
E/pH
6.8
W
ater,900
m
L
0.5%
SDS/W
ater
0.5%
PO
E/W
ater
0.2%
CTAB/W
ater
Time,Minutes
>~25% Dissolved
>~50% Dissolved
11. Reference Compound – Acetaminophen
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
11
• Tylenol 250 mg
Tablet was used as
the test drug
• Size 0 HGC Used for
the OE sample
without filler
12. Tablet vs. OE Capsule Dissolution – Typical Media
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
12
Gelatin Dissolution Research - Acetaminophen, 0.1N HCl
0
20
40
60
80
100
120
0 5 10 15 20 25 30
Time, Min.
%LC
HGC Shell Tylenol OE Capsule Tylenol Tablet
Gelatin Dissolution Research - Acetaminophen, Water
0
20
40
60
80
100
120
0 5 10 15 20 25 30
Time, Min.
%LC
HGC Shell Tylenol OE Capsule Tylenol Tablet
Gelatin Dissolution Research - Acetaminophen, pH 6.8
0
20
40
60
80
100
120
0 5 10 15 20 25 30
Time, Min.
%LC
HGC Shell Tylenol OE Capsule Tylenol Tablet
Gelatin Dissolution Research - Acetaminophen, pH 4.5
0
20
40
60
80
100
120
0 5 10 15 20 25 30
Time, Min.
%LC
HGC Shell Tylenol OE Capsule Tylenol Tablet
Full release (>85%) within
3 minutes from Tablet
(for all conditions)
Once capsule opens, the
residual gelatin does not
impact dissolution for this
product.
Full release (>85%) within
10 minutes from OE
Capsule (for all conditions)
0.1N HCl pH 4.5
pH 6.8 Water
13. Acetaminophen OE Capsule Dissolution –
Surfactant Impact (in Water)
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
13
• Surfactant
somewhat
delays the drug
release
• SDS: high
capsule-to-
capsule
variability
• However, all
conditions
release >85% in
10 minutes
Gelatin Dissolution Research - Acetaminophen OE Capsule,
Surfactant Impact (in Water)
0
20
40
60
80
100
120
0 5 10 15 20 25 30
Time, Min.
%LC
Water Only 0.5% Tween-80 0.5% POE 0.5% CTAB 0.5% SDS
14. Acetaminophen OE Capsule Dissolution –
Surfactant Impact (in 0.1N HCl)
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
14
• Surfactants do
NOT slow down
the drug release
in 0.1N HCL
• CTAB and POE
show slightly
faster drug
release rate
(Very low gelatin
dissolution rate in
0.5% SDS/HCl does
not impact the
drug release from
OE Capsules – see
slide #16)
Gelatin Dissolution Research - Acetaminophen OE Capsule,
Surfactant Impact (in 0.1N HCl)
0
20
40
60
80
100
120
0 5 10 15 20 25 30
Time, Min.
%LC
0.1N HCl only 0.5% SDS 0.5% CTAB 0.5% POE Gelatin_SDS/HCl
15. Acetaminophen OE Capsule Dissolution –
Surfactant Impact (in pH 6.8 Phosphate)
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
15
• CTAB delays the
capsule opening
(> 5minutes)
• SDS shows very
high capsule-to-
capsule
variability, and
did not release
>85% at 10
minutes
Gelatin Dissolution Research - Acetaminophen OE Capsule,
Surfactant Impact (in pH 6.8 Phosphate)
0
20
40
60
80
100
120
0 5 10 15 20 25 30
Time, Min.
%LC
pH 6.8 Phosphate only 0.5% SDS 0.5% CTAB 0.5% POE
16. Acetaminophen OE Capsule Dissolution –
SDS (at 0.5%) Impact in Different Media
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
16
• More variable
in water and pH
6.8 Phosphate
• SDS/pH 6.8: did
not release
>85% at 10
minutes
• However, all
conditions can
release >85% of
drug in 15
minutes
Gelatin Dissolution Research - Acetaminophen OE Capsule,
SDS Impact in Various Media
0
20
40
60
80
100
120
0 5 10 15 20 25 30
Time, Min.
%LC
Water Only SDS in Water SDS in HCl SDS in pH 6.8
17. Comparison of Acetaminophen Dissolution Time:
Tablet vs. OE Capsule in Various Media
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
17
• The Tablet full releases the drug within 3 minutes (> 90% for all media tested)
• The OE Capsule releases >85% drug within 10 minutes for all conditions tested
Acetaminophen Dissolution Comparison - Tablet vs. OE Capsule (Tier-1)
0
1
2
3
4
5
6
7
8
9
10
0.1N
H
Cl, Tablet
0.1N
H
Cl, O
E
C
apsule
0.5%
SDS/0.1N
H
C
l_C
ap
pH
4.5, Tablet
pH
4.5, O
E
Capsule
pH
6.8, Tablet
pH
6.8, O
E
Capsule
0.5%
CTAB/pH
6.8_C
ap
W
ater, Tablet
0.5%
Tween-80, Tablet
W
ater, O
E
C
apsule
0.5%
Tween-80, O
E
C
ap
0.5%
SDS, O
E
C
apsule
0.5%
PO
E, O
E
C
apsule
0.5%
CTAB, O
E
C
apsule
Time,Minutes
>=5% Release >=85% Released
19. Enzymes Information (Currently in USP <711>)
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
19
Pepsin:
• Manufacture: American
Laboratories Inc.
• Product: Pepsin, 1:10,000
Powder
• Lot No: 00511010
• Pepsin Activity: 1:10,400
Pacreatin:
• Manufacture: American
Laboratories Inc.
• Product: Pancreatin 8X USP
Powder
• Lot No: 52320708
• Activity:
Protease: 8.1X USP (203 USP units/mg)
Amylase: 10.2X USP
(255 USP units/mg)
Lipase: 33.7 USP Units/mg
20. Enzymes Information (New)
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
20
Bromelain:
• Manufacture: American
Laboratories Inc.
• Product: Bromelain 2400 GDU
• Lot No: 55920701-A
• Proteolytic Activity:
2,482 GDU/g
Papain:
• Manufacture: American
Laboratories Inc.
• Product: Papain Full Strength
• Lot No: 70310665-B
• Proteolytic Activity:
66,900 USP units/mg
21. Control of Experiments
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
21
Need to get Reproducible results! (Consistency!)
• Same Equipment and Apparatus
• Same Analyst
• Consistent Execution of Dissolution Runs
• Direct Detection – Avoid sampling errors
• Precise operation for generating cross-linked capsule
samples: 2-hour Treatment with Formaldehyde
22. <711> Tier-1 vs. Tier-2:
Non-cross-linked Capsules
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
22
• No significant
difference after 10
minutes
Normal Capsule - 0.1N HCl
0
20
40
60
80
100
120
0 10 20 30 40 50 60
Time, Minutes
%LC
0.1N HCl/Pepsin 0.1N HCl
Normal Capsule - pH 6.8
0
20
40
60
80
100
120
0 10 20 30 40 50 60
Time, Minutes
%LC
pH 6.8 pH 6.8/Pancreatin
Q: NLT 80% in 30 min.
23. Tier-1, 0.1N HCl:
Non-cross-linked Capsule vs. Cross-linked Capsule
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
23
• Fails Stage-3!
• The ~same
level of cross-
linked capsule
samples (i.e. 2-
hour treated)
were used for
all Tier-2
experiments
Tier-1, 0.1N HCl: Normal Capsule vs. X-linked Capsule
0
20
40
60
80
100
120
0 10 20 30 40 50 60
Time, Minutes
%LC
Normal_Tier-1_HCl Xlinked_Tier-1_HCl
Q: NLT 80% in 30 min.
24. Tier-1, pH 6.8:
Non-cross-linked Capsule vs. Cross-linked Capsule
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
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• Fails Stage-3!Tier-1, pH 6.8: Normal Capsule vs. X-linked Capsule
0
20
40
60
80
100
120
0 10 20 30 40 50 60
Time, Minutes
%LC
Normal_Tier-1_pH 6.8 Xlinked_Tier-1_pH 6.8
Q: NLT 80% in 30 min.
25. <711> Pepsin, 750,000 Units/L
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
25
• Current <711>
750,000 units/L
is equivalent to
16,000,000 FCC
units/L
• For X-linked
capsule (2-hour
treated with
formaldehyde),
Tier-2 result at
30 minutes is
92% (± 6.2%)
May Pass S-1
of Tier-2
<711> Pepsin @ 750,000 Units/L
0
20
40
60
80
100
120
0 10 20 30 40 50 60
Time, Minutes
%LC
Normal_Tier-1_HCl Xlinked_Tier-2_HCl
26. <711> Pancreatin, 1750 Units/L
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
26
• Current <711>
1750 units/L
• For X-linked
capsule (2-hour
treated with
formaldehyde),
Tier-2 result at
30 minutes is
83% (± 10.6%)
Will go to
Stage-2 of
Tier-2
<711> Pacreatin @ 1750 Units/L
0
20
40
60
80
100
120
0 10 20 30 40 50 60
Time, Minutes
%LC
Normal_Tier-1_pH 6.8 Xlinked_Tier-2_pH 6.8
27. Finding Equivalent Pancreatin Level to Match
Pepsin Performance
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
27
• Current <711>
1750 units/L
(1X)
• Levels tested:
[Units/L]
1750 (1X), 2000,
2500, 3500 (2X),
and 5250 (3X)
• For 2000 Units/L,
Tier-2 result at
30 minutes is
93% (± 4.0%)
May Pass S-1
of Tier-2
pH 6.8 / Pancreatin
0
20
40
60
80
100
120
0 10 20 30 40 50 60
Time, Minutes
%LC
Normal_Tier-2 Normal_Tier-1 Xlinked_Tier-1
Xlinked_Tier-2_3X Xlinked_Tier-2_2X Xlinked_Tier-2_1X
Xlinked_Tier-2_2500U Xlinked_Tier-2_2000U
1750 Units/L
2000 Units/L
5250 Units/L (3X)
32. Screening Papain at pH 4.5 to Match Pepsin
Performance
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
32
• Starting point:
9 mg/L (i.e.
~600,000 U/L)
• Levels tested:
[KU/L]
600, 550, 525,
and 500 KU/L
• Very small
amount of
Papain Used:
pH 4.5 / Papain
0
20
40
60
80
100
0 10 20 30 40 50 60
Time, Minutes
%LC
Normal_T1 X_T1 X_Tier-2 (600KU)
X_Tier-2 (550KU-1) X_Tier-2 (550KU-2) X_Tier-2 (525KU-1)
X_Tier-2 (525KU-2) X_Tier-2 (500KU)
Units/L mg / 6L
600,000 53.8
550,000 49.3
525,000 47.1
500,000 44.9
33. Screening Papain at pH 4.5 to Match Pepsin
Performance (cont.)
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
33
• The results seem
more variable
than Bromelain
• For 550 KU/L,
Tier-2 result at
30 minutes is
95% (± 3.0%)
Too Good?
• For 525 KU/L,
Tier-2 result at
30 minutes is
85% (± 9.9%)
Will go to
Stage-2 of Tier-2
pH 4.5 / Papain
0
20
40
60
80
100
0 10 20 30 40 50 60
Time, Minutes
%LC
Normal_T1 X_T1 X_Tier-2 (600KU)
X_Tier-2 (550KU, N=12) X_Tier-2 (525KU, N=12)
525 KU/L
35. Stability of Papain Medium at 550,000 Units/L
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
35
• X-linked Capsule
/ Tier-2 Testing:
Levels =
550 KU/L
• After 7 hours,
Tier-2 result at
30 minutes is
78% (± 15.3%)
May Fail the
Tier-2
pH 4.5 / Papain, ~550 KU/L
0
20
40
60
80
100
0 10 20 30 40 50 60
Time, Minutes
%LC
Papain 550 kU-1 Papain 550 kU-2 Papain 550 kU_7 Hours
36. Stability of Papain Medium at 525,000 Units/L
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
36
• X-linked Capsule
/ Tier-2 Testing:
Levels =
525 KU/L
• Up to 4 hours,
the dissolution
rate did not slow
down
• Overall, it shows
high variability
from run-to-run
using Papain at
550 KU/L and
525 KU/L
pH 4.5 / Papain, ~525 KU/L
0
20
40
60
80
100
0 10 20 30 40 50 60
Time, Minutes
%LC
Papain 525 kU-1 Papain 525 kU-2 Papain 525 kU_4 Hours
37. Stability of Bromelain Medium at 30 GDU/L
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
37
• X-linked Capsule
/ Tier-2 Testing:
Levels =
30 GDU/L
• The dissolution
rate are very
consistent up to
4 hours
• After 7 hours,
Tier-2 result at
30 minutes is
70% (± 9.6%)
May Fail the
Tier-2
pH 4.5 / Bromelain, ~30 GDU/L
0
20
40
60
80
100
0 10 20 30 40 50 60
Time, Minutes
%LC
Bromelain 30GDU-1 Bromelain 30GDU-2
Bromelain 30GDU_4-hour Bromelain 30GDU_7-hour
38. Solution Stability of Enzyme Media
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
38
• Enzyme activity will drop over time in solution
• From the observations of Bromelain and Papain media, it
suggests that the dissolution run should start within 4 hours
after the media is made. The media is no longer good after 7
hours.
• Pepsin and Pancreatin had not been tested for solution stability,
but the general rule from above may apply to them
39. Disintegration Evaluation:
Another Look from Different Hydrodynamics
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
39
• Bromelain @30 GDU/L
and Papain @525
KU/L have much
longer disintegration
time than Pepsin
• @6X works well (6
capsules in 1 beaker)
Disintegration of Cross-linked Capsules
(Individual Data)
0
5
10
15
20
25
30
W
ater
SG
F
SIF
Pepsin,1XPancreatin,1XBrom
elain,1X
Papain,1XBrom
elain,6X
Papain,6X
DisintegrationTime,Min.
0
2
4
6
8
10
12
14
16
18
20
W
ater
SG
F
SIF
Pepsin, 1X
Pancreatin, 1X
Brom
elain, 1X
Papain, 1X
Brom
elain, 6X
Papain, 6X
Disintegration of Cross-linked Capsules (Mean, N=6)
• Water can not open the X-linked
capsules within 15 minutes
• Pancreatin @1750 units/L is
weaker than SGF and Pepsin
(similar to dissolution results)
40. Summary: Recommended Levels of these four
Enzymes
Recommended
levels of
Enzymes:
•Pepsin: 750,000
Units/L (<711>),
i.e. 16,000,000
FCC units/L
•Pancreatin:
2000 Units/L
•Bromelain:
30 GDU/L
•Papain: 550,000
Units/L
(525,000 U/L may
be slightly too
weak and too
variable.)
40
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
Tier-2 Performance Comparison - All 4 Enzymes (N=12)
0
20
40
60
80
100
0 10 20 30 40 50 60
Time, Minutes
%LC
Pepsin/750000 U Pancreatin/2000 U
Bromelain/30 GDU Papain/550000 U
Normal Capsule (pH 6.8)
Tier-2 Performance Comparison - All 4 Enzymes (N=12)
0
20
40
60
80
100
0 10 20 30 40 50 60
Time, Minutes
%LC
Pepsin/750000 U Pancreatin/2000 U Bromelain/30 GDU Papain/525000 U
41. Summary and Next Step
• The gelatin dissolves faster in 0.1N HCl than pH 4.5 & pH 6.8
• SDS may interact with gelatin and show more variable results. The
impact is not significant for fast dissolving formulations
• Pepsin in 0.1N HCl is used as the reference, and identified the
appropriate levels for the other three enzymes
Next Steps:
• Verify these experiment results from other labs
• Verify working pH ranges for each enzymes
• Find the best way to express the enzyme activity, and be consistent
from various suppliers
41
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013
42. • 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, Rio de Janeiro-Brazil, 2013
42
43. Acknowledgement
• Dr. Jian-Hwa Han is employed at Abbvie. Dr. Han is the primary
investigator for this study.
• Mr. Daniel Bonilla is employed at Abbvie. Mr. Bonilla provided
technical assistance for this study.
• Ms. Susan George and Dr. Paul D. Curry, Jr. are employed at Abbvie
who have contributed for scientific discussions and reviewing the
presentation materials.
• Mr. Thomas Langdon of American Laboratories, Inc. provided all
four enzymes for this study, and the technical information about
these materials.
43
USP Dissolution Workshop, Rio de Janeiro-Brazil, 2013