Watch the presentation of this webinar here: bit.ly39Rd5Xd
Amorphous formulations provide unparalleled solubility advantages. However, physical stability of the molecule in the formulation is crucial for success. Join this webinar to learn the advantages and risks of amorphous formulations and strategies for ensuring stabilization of challenging compounds.
Solubility is a major challenge in the development of oral solid dosage forms. Amorphous formulation with polymeric solid dispersions have been the technology of choice to enhance solubility. However, this approach may have some downfalls when considering the ability to successfully stabilize compounds, especially poor glass former compounds with high propensity to re-crystallize. This webinar will examine amorphous stability from a theoretical perspective in the context of polymeric solid dispersions and mesoporous silica formulations. Finally, recent data demonstrating the potential of mesoporous silica for superior amorphous stabilization of poor glass formers will be presented.
In this webinar, you will learn
• Why solubility is a critical consideration in development of oral medication
• How the amorphous form can enhance solubility and increase absorption
• Why some molecules are at risk of re-crystallization with typical polymeric amorphous technologies
• How mesoporous silica can reduce the risk of re-crystallization of poor glass formers
Improving Downstream Processing: Application of Excipients in DSPMilliporeSigma
This study investigates the benefits of adding excipients during downstream processing on protein stability, chromatographic performance and viral inactivation.
High concentration uf formulation challenges & mitigation strategies by s...Merck Life Sciences
Are you working on a high concentration mAb subcutaneous formulation? Join us to find out how to overcome buffer offsets in the formulation UF-DF step.
In this webinar, you will learn:
• High concetnration UF-DF optimization
• Scaling up the UF-DF step
• Models to explain buffer offsets
• Process Development to mitigate buffer offsets
Tangential flow filtration (TFF) using ultrafiltration membranes is commonly used for the final formulation and concentration of monoclonal antibodies. Injection of liquid formulations is often the preferred method of administration for these therapeutics. In cases where high dosages are required, manufacturers frequently target high concentration liquid formulations which can result in high viscosity solutions. Highly concentrated protein solutions have challenges associated with formulation. This talk presents the formulation challenges that are associated with plausible risk mitigation strategies to overcome such formulation challenges.
Amorphous formulations for bioavailability enhancement risks and opportunitie...Merck Life Sciences
Watch the presentation of this webinar here: bit.ly/39Rd5Xd
Amorphous formulations provide unparalleled solubility advantages. However, physical stability of the molecule in the formulation is crucial for success. Join this webinar to learn the advantages and risks of amorphous formulations and strategies for ensuring stabilization of challenging compounds.
Solubility is a major challenge in the development of oral solid dosage forms. Amorphous formulation with polymeric solid dispersions have been the technology of choice to enhance solubility. However, this approach may have some downfalls when considering the ability to successfully stabilize compounds, especially poor glass former compounds with high propensity to re-crystallize. This webinar will examine amorphous stability from a theoretical perspective in the context of polymeric solid dispersions and mesoporous silica formulations. Finally, recent data demonstrating the potential of mesoporous silica for superior amorphous stabilization of poor glass formers will be presented.
In this webinar, you will learn
• Why solubility is a critical consideration in development of oral medication
• How the amorphous form can enhance solubility and increase absorption
• Why some molecules are at risk of re-crystallization with typical polymeric amorphous technologies
• How mesoporous silica can reduce the risk of re-crystallization of poor glass formers
Long acting injectable microparticle formulation - a new dimension for peptid...Merck Life Sciences
Explore the clinical benefits and applications of sustained release drug delivery with this presentation. Access the findings from a technical feasibility study as well as a case study on sustained release microparticle formulation for a sensitive peptide.
This presentation reviews the results of a study in which the authors investigated the effects of poly-diallydimethylammonium chloride (pDADMAC) flocculation and clarification on the performance and longevity of protein A resin.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: http://www.emdmillipore.com/mlab
This presentation provides an introduction to the M Lab™ Collaboration Centers, an overview of chromatography theory, and highlights the benefits of next-generation chromatography.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/mlab
Improving Downstream Processing: Application of Excipients in DSPMilliporeSigma
This study investigates the benefits of adding excipients during downstream processing on protein stability, chromatographic performance and viral inactivation.
High concentration uf formulation challenges & mitigation strategies by s...Merck Life Sciences
Are you working on a high concentration mAb subcutaneous formulation? Join us to find out how to overcome buffer offsets in the formulation UF-DF step.
In this webinar, you will learn:
• High concetnration UF-DF optimization
• Scaling up the UF-DF step
• Models to explain buffer offsets
• Process Development to mitigate buffer offsets
Tangential flow filtration (TFF) using ultrafiltration membranes is commonly used for the final formulation and concentration of monoclonal antibodies. Injection of liquid formulations is often the preferred method of administration for these therapeutics. In cases where high dosages are required, manufacturers frequently target high concentration liquid formulations which can result in high viscosity solutions. Highly concentrated protein solutions have challenges associated with formulation. This talk presents the formulation challenges that are associated with plausible risk mitigation strategies to overcome such formulation challenges.
Amorphous formulations for bioavailability enhancement risks and opportunitie...Merck Life Sciences
Watch the presentation of this webinar here: bit.ly/39Rd5Xd
Amorphous formulations provide unparalleled solubility advantages. However, physical stability of the molecule in the formulation is crucial for success. Join this webinar to learn the advantages and risks of amorphous formulations and strategies for ensuring stabilization of challenging compounds.
Solubility is a major challenge in the development of oral solid dosage forms. Amorphous formulation with polymeric solid dispersions have been the technology of choice to enhance solubility. However, this approach may have some downfalls when considering the ability to successfully stabilize compounds, especially poor glass former compounds with high propensity to re-crystallize. This webinar will examine amorphous stability from a theoretical perspective in the context of polymeric solid dispersions and mesoporous silica formulations. Finally, recent data demonstrating the potential of mesoporous silica for superior amorphous stabilization of poor glass formers will be presented.
In this webinar, you will learn
• Why solubility is a critical consideration in development of oral medication
• How the amorphous form can enhance solubility and increase absorption
• Why some molecules are at risk of re-crystallization with typical polymeric amorphous technologies
• How mesoporous silica can reduce the risk of re-crystallization of poor glass formers
Long acting injectable microparticle formulation - a new dimension for peptid...Merck Life Sciences
Explore the clinical benefits and applications of sustained release drug delivery with this presentation. Access the findings from a technical feasibility study as well as a case study on sustained release microparticle formulation for a sensitive peptide.
This presentation reviews the results of a study in which the authors investigated the effects of poly-diallydimethylammonium chloride (pDADMAC) flocculation and clarification on the performance and longevity of protein A resin.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: http://www.emdmillipore.com/mlab
This presentation provides an introduction to the M Lab™ Collaboration Centers, an overview of chromatography theory, and highlights the benefits of next-generation chromatography.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/mlab
The biopharmaceutical industry needs high-performance processing through the establishment of next-generation solutions to improve efficiency and effectiveness. The shift in the industry toward efficient monoclonal antibody (mAb) processing has necessitated the development of novel approaches.
In this webinar, you will learn:
• What benefits upstream process intensification brings to the manufactures addition to higher productivity
• Several scenarios with process modeling data to quantify financial benefits and value
• Perfused seed train process development data taken with our new Cellicon™ Solution and Cellvento® 4CHO-X expansion medium
Upstream process intensification can bring significant benefits to manufacturers in terms of smaller facilities, manufacturing flexibility, and reduction in footprint, with achieving significantly higher productivity. Several scenarios for Mab production become apparent with the implementation of perfusion-based operations, especially for the seed train. We will identify these scenarios with process modeling data to quantify their financial benefits and value. In addition, we will share perfused seed train process development data resulting from the use of our new Cellicon™ Solution and Cellvento® 4CHO-X expansion medium.
In this webinar, you will learn:
- The key issues in continuous manufacturing concerning excipients
- How those issues can be addressed
Detailed description:
Continuous manufacturing is a major trend in solid dose formulation. It shows economic and quality benefits, however, hurdles and challenges need to be tackled before getting there. This webinar will address these hurdles and challenges as they relate to excipients.
We will present how continuous manufacturing lines are set up and the benefits users have experienced from them. Feeding of especially small components of formulation combined with bad flow is a major challenge, as well as having a high number of components leading to many feeders. Our answer to these challenges are threefold: betting on multifunctional excipients, and on premixes, either as finished products or as customized projects.
This presentation reviews the results of a study in which the authors investigated the effects of poly-diallydimethylammonium chloride (pDADMAC) flocculation and clarification on the performance and longevity of protein A resin.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: http://www.merckmillipore.com/mlab
Solubilisation of Quinazoline drugs by using Beta cyclodextrin complex formationRavindra Zirmire
Solubility of the Quinazoline related drugs was enhanced by usind complex formation method,and the Physico chemical characterisation of these drugs was carried out by simplest methods as UV spectroscopy,TLC,FTIR Spectroscopy.
Prof Alastair Florence
Presentation at EIPG - Royal Pharmaceutical Society Scientific Symposium "Advances in Technology Impacting the Pharmaceutical Industry" at the University of Strathclyde, Glasgow 2015.
Comparison of Lyophilisation Cycles for a BNCT agent using "traditional" and ...BTL
Two freeze drying cycles were designed, one by "traditional" methods, and one by SMART (R) Freeze Drying Technology developed by SP Scientific. The cycles were then analysed for efficacy and efficiency. This study was carried out by the University of Strathclyde.
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
Solubility Enhancement, Stability and Scalability of Mesoporous Silica Formul...Merck Life Sciences
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
Hot melt extrusion with PVA – solubility enhancement, supersaturation perform...MilliporeSigma
Hot melt extrusion has successfully emerged as an innovative manufacturing technology in pharmaceutical industry for the creation of amorphous solid dispersions (ASDs).
In this webinar you will learn about the potential of hot melt extrusion to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA) as a matrix polymer. We will provide an overview about different types of solid dispersions and their evolution in the pharmaceutical field. A brief introduction in hot melt extrusion processing will be given as well as actual formulation trends. You will get insights in potential down-stream options to create your final dosage form and you will gain ideas on how to speed up your formulation development.
A detailed background of PVA will be provided including its physical properties as well as its regulatory status. PVA is more than a polymer. Due to its amphiphilic structure it has the potential to improve the supersaturation of low soluble APIs and to prevent precipitation after release. This highlights the versatility of PVA as an advanced polymer for HME applications and we will guide you through our latest research activities so that you can leverage our knowledge to improve your formulations.
This webinar includes:
- The current status and further potential of HME in pharmaceutical industry
- Advantages of PVA in the field of ASDs: Solubility improvement, impact on supersaturation potential, stability data generated on sample formulations & downstream options
- Deep dive into latest research activities: Permeation studies with Caco-2 cell membranes, pH shift studies to investigate supersaturation potential, ongoing research activities to get to know a more detailed understanding of matrix systems and their intermolecular interactions
In this webinar, you will learn:
- which potential hot melt extrusion has, to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA)
- why PVA is more than just a polymer
- how to create your final dosage form and speed up your formulation development
The biopharmaceutical industry needs high-performance processing through the establishment of next-generation solutions to improve efficiency and effectiveness. The shift in the industry toward efficient monoclonal antibody (mAb) processing has necessitated the development of novel approaches.
In this webinar, you will learn:
• What benefits upstream process intensification brings to the manufactures addition to higher productivity
• Several scenarios with process modeling data to quantify financial benefits and value
• Perfused seed train process development data taken with our new Cellicon™ Solution and Cellvento® 4CHO-X expansion medium
Upstream process intensification can bring significant benefits to manufacturers in terms of smaller facilities, manufacturing flexibility, and reduction in footprint, with achieving significantly higher productivity. Several scenarios for Mab production become apparent with the implementation of perfusion-based operations, especially for the seed train. We will identify these scenarios with process modeling data to quantify their financial benefits and value. In addition, we will share perfused seed train process development data resulting from the use of our new Cellicon™ Solution and Cellvento® 4CHO-X expansion medium.
In this webinar, you will learn:
- The key issues in continuous manufacturing concerning excipients
- How those issues can be addressed
Detailed description:
Continuous manufacturing is a major trend in solid dose formulation. It shows economic and quality benefits, however, hurdles and challenges need to be tackled before getting there. This webinar will address these hurdles and challenges as they relate to excipients.
We will present how continuous manufacturing lines are set up and the benefits users have experienced from them. Feeding of especially small components of formulation combined with bad flow is a major challenge, as well as having a high number of components leading to many feeders. Our answer to these challenges are threefold: betting on multifunctional excipients, and on premixes, either as finished products or as customized projects.
This presentation reviews the results of a study in which the authors investigated the effects of poly-diallydimethylammonium chloride (pDADMAC) flocculation and clarification on the performance and longevity of protein A resin.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: http://www.merckmillipore.com/mlab
Solubilisation of Quinazoline drugs by using Beta cyclodextrin complex formationRavindra Zirmire
Solubility of the Quinazoline related drugs was enhanced by usind complex formation method,and the Physico chemical characterisation of these drugs was carried out by simplest methods as UV spectroscopy,TLC,FTIR Spectroscopy.
Prof Alastair Florence
Presentation at EIPG - Royal Pharmaceutical Society Scientific Symposium "Advances in Technology Impacting the Pharmaceutical Industry" at the University of Strathclyde, Glasgow 2015.
Comparison of Lyophilisation Cycles for a BNCT agent using "traditional" and ...BTL
Two freeze drying cycles were designed, one by "traditional" methods, and one by SMART (R) Freeze Drying Technology developed by SP Scientific. The cycles were then analysed for efficacy and efficiency. This study was carried out by the University of Strathclyde.
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
Solubility Enhancement, Stability and Scalability of Mesoporous Silica Formul...Merck Life Sciences
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
Hot melt extrusion with PVA – solubility enhancement, supersaturation perform...MilliporeSigma
Hot melt extrusion has successfully emerged as an innovative manufacturing technology in pharmaceutical industry for the creation of amorphous solid dispersions (ASDs).
In this webinar you will learn about the potential of hot melt extrusion to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA) as a matrix polymer. We will provide an overview about different types of solid dispersions and their evolution in the pharmaceutical field. A brief introduction in hot melt extrusion processing will be given as well as actual formulation trends. You will get insights in potential down-stream options to create your final dosage form and you will gain ideas on how to speed up your formulation development.
A detailed background of PVA will be provided including its physical properties as well as its regulatory status. PVA is more than a polymer. Due to its amphiphilic structure it has the potential to improve the supersaturation of low soluble APIs and to prevent precipitation after release. This highlights the versatility of PVA as an advanced polymer for HME applications and we will guide you through our latest research activities so that you can leverage our knowledge to improve your formulations.
This webinar includes:
- The current status and further potential of HME in pharmaceutical industry
- Advantages of PVA in the field of ASDs: Solubility improvement, impact on supersaturation potential, stability data generated on sample formulations & downstream options
- Deep dive into latest research activities: Permeation studies with Caco-2 cell membranes, pH shift studies to investigate supersaturation potential, ongoing research activities to get to know a more detailed understanding of matrix systems and their intermolecular interactions
In this webinar, you will learn:
- which potential hot melt extrusion has, to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA)
- why PVA is more than just a polymer
- how to create your final dosage form and speed up your formulation development
Hot melt extrusion with PVA – solubility enhancement, supersaturation perform...Merck Life Sciences
Hot melt extrusion has successfully emerged as an innovative manufacturing technology in pharmaceutical industry for the creation of amorphous solid dispersions (ASDs).
In this webinar you will learn about the potential of hot melt extrusion to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA) as a matrix polymer. We will provide an overview about different types of solid dispersions and their evolution in the pharmaceutical field. A brief introduction in hot melt extrusion processing will be given as well as actual formulation trends. You will get insights in potential down-stream options to create your final dosage form and you will gain ideas on how to speed up your formulation development.
A detailed background of PVA will be provided including its physical properties as well as its regulatory status. PVA is more than a polymer. Due to its amphiphilic structure it has the potential to improve the supersaturation of low soluble APIs and to prevent precipitation after release. This highlights the versatility of PVA as an advanced polymer for HME applications and we will guide you through our latest research activities so that you can leverage our knowledge to improve your formulations.
This webinar includes:
- The current status and further potential of HME in pharmaceutical industry
- Advantages of PVA in the field of ASDs: Solubility improvement, impact on supersaturation potential, stability data generated on sample formulations & downstream options
- Deep dive into latest research activities: Permeation studies with Caco-2 cell membranes, pH shift studies to investigate supersaturation potential, ongoing research activities to get to know a more detailed understanding of matrix systems and their intermolecular interactions
In this webinar, you will learn:
- which potential hot melt extrusion has, to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA)
- why PVA is more than just a polymer
- how to create your final dosage form and speed up your formulation development
Formulation, Development and Evaluation of Fast Disintegrating Tablet of Piro...ijtsrd
The solubility behavior of drugs remains one of the most exigent aspects in formulation development. With the advent of combinatorial chemistry and high throughput screening, the number of poorly water soluble compounds has dramatically increased. Among all the newly discovered chemical entities, about 40 45 drugs fail to reach market due to their poor water solubility. Because of solubility problem, bioavailability of drugs gets affected and hence solubility enhancement becomes necessary. In present study the attempts have been made to increase the dissolution of BCS class 2 drug Piroxicam using hydrophilic polymers namely polyethylene glycol PEG 6000 and sodium lauryl sulphate as a surfactant by using solid dispersion technique. In solid dispersion microwave induced solid dispersion and conventional fusion method is compared. Drug polymer complex was prepared using batch method. Maximum dissolution rate was obtained of the complex prepared from Piroxicam PEG6000 SLS . A successful solubility enhancement of drug complex was confirmed by taking drug release in phosphate buffer pH 6.8. The drug was characterized according to different compendial methods, on the basis of identification by UV spectroscopy, organoleptic properties and other tests. After that among the all formulation batches, solid dispersion F16 was selected for further tablet formulation batches, nine formulations were developed and studied. The values of pre compression parameters was evaluated, results were within prescribed limits and indicated good free flowing properties. The data obtained of post compression parameters such as weight variation, hardness, friability, wetting time, water absorption ratio, content uniformity, disintegration time and dissolution was found to superior over conventional formulation. The F9 batch with disintegrating time 10 ± 0.52 second and dissolution 93.20 ± 0.61 was selected as optimized formulation and was found superior over other formulation. Batch F9 was also subjected to stability studies for three months and was tested for its disintegrating time, drug contents and dissolution behavior monthly. F9 formulation after stability study was found to be stable. Mr. Yennuwar Dhiresh Pramod | Mr. Sujit Kakade | Mrs. Trusha Shangrapawar | Dr. Ashok Bhosale "Formulation, Development and Evaluation of Fast Disintegrating Tablet of Piroxicam using Solid Dispersion Technique" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-5 , August 2022, URL: https://www.ijtsrd.com/papers/ijtsrd50422.pdf Paper URL: https://www.ijtsrd.com/pharmacy/pharmaceutics/50422/formulation-development-and-evaluation-of-fast-disintegrating-tablet-of-piroxicam-using-solid-dispersion-technique/mr-yennuwar-dhiresh-pramod
Dissolution enhancement of glimepiride by solid dispersion technique.Santosh Adhikari
Dissolution Enhancement of Glimepiride by Solid Dispersion Technique.
Priyanka Shrestha1*, Shiva Kumar Bhandari1, SM Ashraful Islam1, and Santosh Adhikari2.
1Department of Pharmacy, University of Asia Pacific, Dhanmondi, Dhaka-1209, Bangladesh.
2Department of Pharmacy, Rajiv Gandhi University of Health Science, Banglore-560 041.
Excipients selection for high risk formulations Smita RajputMerck Life Sciences
Are you choosing the right excipients for your high risk application? Find out how to select the right excipients and enable your process optimization to improve the total cost of ownership.
In this webinar, you will learn:
• Selection of right excipients for high risk formulation is very critical step
• Low Endotoxin and low bioburden limits are important aspect while selecting raw materials
• Strong regulatory support is crucial for high risk formulation
Excipients selection for high risk formulations like parenteral and ophthalmic applications is very challenging. Excipients should be inert with high purity for such dosage forms because trace amounts of impurities present in excipients can interact with active pharmaceutical ingredient (API) which results in instability of the formulation. This presentation discusses how to select the right excipients for high-risk applications and gives guidance for process optimization by choosing the best combination of filters and excipients to improve the total cost of ownership.
Excipients selection for high risk formulations Smita RajputMilliporeSigma
Are you choosing the right excipients for your high risk application? Find out how to select the right excipients and enable your process optimization to improve the total cost of ownership.
In this webinar, you will learn:
• Selection of right excipients for high risk formulation is very critical step
• Low Endotoxin and low bioburden limits are important aspect while selecting raw materials
• Strong regulatory support is crucial for high risk formulation
Excipients selection for high risk formulations like parenteral and ophthalmic applications is very challenging. Excipients should be inert with high purity for such dosage forms because trace amounts of impurities present in excipients can interact with active pharmaceutical ingredient (API) which results in instability of the formulation. This presentation discusses how to select the right excipients for high-risk applications and gives guidance for process optimization by choosing the best combination of filters and excipients to improve the total cost of ownership.
The Importance of Amorphous Stability: Mesoporous Silica for Poor Glass FormersMerck Life Sciences
Access the interactive recording: https://bit.ly/2SApPJr
Abstract: Historically, polymeric solid dispersions have been the technology of choice for amorphous formulation. However, this approach may have some downfalls when considering the ability to stabilize compounds in the amorphous form, especially poor glass former compounds with high propensity to re-crystallize. This webinar will examine amorphous stability from a theoretical perspective in the context of polymeric solid dispersions and mesoporous silica formulations. Finally, we will present recent data demonstrating the potential of mesoporous silica for superior amorphous stabilization of poor glass formers.
The Importance of Amorphous Stability: Mesoporous Silica for Poor Glass FormersMilliporeSigma
Access the interactive recording: https://bit.ly/2SApPJr
Abstract: Historically, polymeric solid dispersions have been the technology of choice for amorphous formulation. However, this approach may have some downfalls when considering the ability to stabilize compounds in the amorphous form, especially poor glass former compounds with high propensity to re-crystallize. This webinar will examine amorphous stability from a theoretical perspective in the context of polymeric solid dispersions and mesoporous silica formulations. Finally, we will present recent data demonstrating the potential of mesoporous silica for superior amorphous stabilization of poor glass formers.
The term solid dispersion refers to a group of solid products consisting of a hydrophilic matrix and a hydrophobic drug frequently prepared by fusion solvent method. The matrix can be amorphous or crystalline in nature .
The Viscosity Reduction Platform: Viscosity-reducing excipients for improveme...MilliporeSigma
Protein viscosity is a major challenge in preparing highly concentrated protein formulations suitable for subcutaneous injection. Recently, the Viscosity Reduction Platform (VRP) was introduced and its technical key features and benefits for formulations were discussed. However, highly viscous solutions do not only pose a challenge when administering a drug to a patient, they can also impose technical limitations in the manufacturing process.
This white paper evaluates the effect of the excipients in the Viscosity Reduction Platform on ultrafiltration processes used to produce a highly concentrated formulation of a monoclonal antibody (mAb). Two filtration methods are demonstrated in this work.
Find more information about the Viscosity Reduction Platform on our website: https://www.sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Use of Excipients in Downstream Processing to Improve Protein PurificationMilliporeSigma
Excipients are used to improve the stability of protein-based therapeutics by protecting the protein against a range of stress conditions such as temperature changes, pH changes, or agitation. Similar stresses are applied to proteins during downstream purification. Shifts in pH during Protein A chromatography, subsequent incubations at low pH for virus inactivation, and changes in conductivity in ion exchange chromatography can lead to aggregation, fragmentation, or other chemical modifications of the therapeutic protein. Given the potential impact on the protein’s structural integrity, there is a need for approaches to reduce the risk presented by the conditions during downstream processing. For example, integration of a solution to prevent aggregation of proteins would be a more efficient strategy than implementing steps to remove multimeric forms.
This white paper highlights the results from a recent paper by Stange et. al., in which protein stabilizing excipients such as polyols, sugars, and polyethylene glycol (PEG4000) were used as buffer system additives. Effect of the excipients on elution patterns, stabilization of the monomer antibody, host-cell protein removal, virus inactivation rates and binding capacity of cation exchange chromatography were explored.
Exploring the protein stabilizing capability of surfactants against agitation...MilliporeSigma
Agitation of therapeutic protein solutions during manufacturing, shipping and handling is one of the major initiators for protein aggregation and particle formation during the life history of a protein drug. Adsorption of protein molecules to liquid-air interfaces leads to the formation of highly concentrated protein surface films. The rupture of these protein films due to various mechanical processes can then result in the appearance of protein aggregates and particles in the bulk solution phase.
One technique to stabilize proteins against stress induced by liquid-air interfaces is the use of non-ionic surfactants. About 91% of antibody formulations commercially available in 2021 contained a surfactant. Polysorbate 20 and 80, composed of a hydrophilic polyoxyethylene sorbitan and hydrophobic fatty acid esters, made up the largest part being employed in 87% of said formulations.
Despite their frequent use in parenteral drug products, concerns have been raised for decades about the application of polysorbates as surfactants in biopharmaceutical formulations. Autoxidation of polysorbate, caused by residual peroxides in polysorbates, can damage the proteins and can further drive the oxidative degradation of polysorbate. Chemical and enzymatic hydrolysis of polysorbate may lead to the formation of free fatty acid particles, which may become visible; and both mechanisms eventually lead to the reduction in polysorbate concentration. Therefore, the purpose of the current study was to compare various molecules for their capabilities to reduced agitation-induced protein aggregation and particle formation; and furthermore, investigate their underlying protein stabilizing mechanisms.
The Viscosity Reduction Platform: Viscosity Reducing Excipients for Protein F...MilliporeSigma
Protein viscosity is one of the major obstacles in preparing highly concentrated protein formulations suitable for subcutaneous injection.
This whitepaper examines how combining an amino acid with a second viscosity-reducing excipient circumvents adverse effects on protein stability and improves viscosity-reducing capacity.
To find more information about the Viscosity Reduction Platform, please visit our website: https://sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Characterization of monoclonal antibodies and Antibody drug conjugates by Sur...MilliporeSigma
Watch the presentation of this webinar: https://bit.ly/3Pjpjvr
Highlights of this webinar:
- Surface plasmon resonance as a powerful tool for biologic characterization including mAbs and ADCs.
- SPR allows rapid binding analysis in real time without using labels for SARS-CoV-2 receptor binding domain mutations.
- Kinetic data is indicative of possible neutralizing activity allowed assessment of neutralizing ability of therapeutic monoclonal antibodies.
- The application can provide preliminarily efficacy information and facilitated mAbs/ACDs candidate selection process
Detailed description:
Characterization of therapeutic monoclonal antibodies (mAbs) or Antibody drug conjugates (ADCs) is challenging due to their ability to bind to a variety of proteins via their Fc and Fab domains, giving rise to diverse biological functions associated with each domain. The Fc domain of mAbs interacts with Fc receptors with varying affinities, which can influence biological processes such as Complement-dependent cytotoxicity (CDC) and Antibody-dependent cellular cytotoxicity (ADCC), transcytosis, phagocytosis, and/or serum half-life.
An important characteristic of an antibody is its Fc effector function. Antibodies can be engineered to obtain desired binding of the Fc region to Fc receptors expressed on effector cells. Hence, it is crucial to evaluate the binding interaction of mAbs/ADC with Fc receptors in the early phase of drug development to understand the potential biological activity of the product in vivo.
Surface Plasmon Resonance (SPR) is a powerful technique to establish binding kinetics in real-time, label free, and high sensitivity with low sample consumption. Along with target antigen binding, it is crucial to evaluate the binding interaction of antibodies and ADCs with Fc receptors. Our SPR case studies investigated the impact on binding kinetics of ADCs with different linkers and the binding interactions of SARS-CoV-2 spike protein variants and evaluated the neutralizing ability of therapeutic mAbs. SPR characterisation can be facilitated in all stages of the product life cycle to ensure the quality and safety of mAbs and ADCs.
The Role of BioPhorum Extractables Data in the Effective Adoption of Single-U...MilliporeSigma
Regulatory expectation does require patient safety evaluations with supporting data for manufacturing components that directly come into contact with drug manufacturing process streams. Readily available extractables data can help manufacturers using singleuse technology to accelerate product qualifications, risk assessments and process optimization
This white paper guides you on how to save time and resources with supplier-provided single-use system extractables data and gives you an overview about the overall strategy for Extractables & Leachables. At the end you will find a case study.
Find more information about filters and single-use components on our website: https://www.sigmaaldrich.com/DE/en/services/product-services/emprove-program/emprove-filter-and-single-use-component-portfolio
The Future of Pharma- and Biopharmaceutical AuditsMilliporeSigma
Watch the recording of this presentation here: https://bit.ly/3zTOpe4
Detailed description:
SARS-CoV-2 showed us that technology supports us during our inspection activity even if on-site visits are not possible. Travel restrictions of various kinds will remain a risk in the future. The use of new technologies has shown that inspections and audits can be carried out despite these restrictions. We will focus on what possibilities the new technologies offer and take a look at the future of inspections and audits.
In this webinar, you will learn:
• Regulatory overview of remote audits
• The technologies needed to support the audit process
• What types of inspections are possible with the use of these technologies
• How audits may look in the future
Presented by:
Daniel Buescher, Product Manager - Digital Solutions
Moving your Gene Therapy from R&D to IND: How to navigate the Regulatory Land...MilliporeSigma
Watch the recording of this presentation here: https://bit.ly/3SqOsoP
Novel therapies, including cell and gene therapies, continue to be central to innovation in healthcare and represent the fastest growing area of therapeutic medicine. As a consequence, the number of gene therapies undergoing clinical trials has increased significantly in the last five years.
Manufacturing processes for these novel therapeutics are very complex with a high risk of contamination. Regulatory agencies world-wide have responded by issuing guidance to outline their expectations for development and manufacture of cell and gene therapies. Currently, regulatory guidance is not harmonized globally and can often lead to confusion within industry and increased risk of non-compliance.
In this webinar, we'll answer:
• Which regulatory guidelines do you need to comply for your INDs?
• When do you start implementing GMPs and validated assays?
• How do you get your QC testing strategy ‘right the first time’?
• How do you ensure testing is not your rate limiting step for the IND submission?
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Dr. Alison Armstrong, Sr. Director, Technical and Scientific Solutions
Identity testing by NGS as a means of risk mitigation for viral gene therapiesMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3RijkHC
Detailed description:
Imagine you’ve just completed a manufacturing run for your viral vector. Identity testing is performed to confirm the vector sequence. But when the results come back the data reveals unexpected sequence variants! With an appropriate risk mitigation testing strategy, this situation can be prevented.
The situation described above is not hypothetical, and happens more that you think, costing valuable time and resources.
Investigatory testing has shown that sequence variants present in starting materials (e.g. plasmids) are likely to make their way to the final product. Adequate identification of low-level variants with an appropriately sensitive method is critical in ensuring the quality of the final product. A risk-based testing strategy, in the context of identity, for viral vector manufacturing will be presented, focusing on key testing points. NGS assays for identity and variant detection will be highlighted due to their extremely sensitive nature compared to traditional approaches.
In this webinar, we'll explore:
• Regulatory requirements for identity testing
• NGS applications for identity testing as compared to traditional methods
• A case study on the impact of not establishing a proper risk-based testing strategy
Presented by: Bradley Hasson, Director of Lab Operations for NGS Services
Latest advancements of melt based 3D printing technologies for oral drug deli...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3A2WcH4
The application of polymer excipients in 3D printing manufacturing is usually limited due to the concerns of filament strength, high processing temperature and large scale manufacturing.
Latest technology developments are targeting a direct melt deposition to simplify the process and enable a constant and efficient process. Two different processing approaches will be presented:
The advanced melt drop deposition, where individual three dimensional geometries can be created by depostition of polymer droplets and the MED® 3D printing technology which allows by precise layer-by-layer deposition to produce objects with well-designed geometric structures.
In this webinar, you will learn:
• Latest advancements of melt based 3D printing approaches
• Application examples for the individual technologies
• Deep dive in the MED® 3D printing technology to design dedicated drug release profiles
Presented by:
Dr. Thomas Kipping, Head of Drug Carriers
Dr. Xianghao Zuo, Deputy Director of R&D, Triastek
CAR-T Manufacturing Innovations that Work - Automating Low Volume Processes a...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3NDNIKe
Automated, fit-for-purpose tools are essential in CAR-T processing to support sustainable manufacturing of clinical and market-approved cell therapy products. This webinar will discuss how the ekko™ Acoustic Cell Processing System uses acoustic technology as a touchless approach to manipulate cells, enabling a modular tool across the CAR-T manufacturing workflow. Typical performance of templated ekko™ System processes for DMSO washout of leukapheresis material, low volume and high cell concentrate for electroporation preparation, and harvest of expanded T cells will be reviewed.
This webinar will also give an early glimpse at the ekko™ Select System for unmatched T cell selection.
In this webinar, you will:
• Uncover how the ekko™ System supports the broad industrialization of cell therapy, with particular focus on how to achieve low volume, high concentrate cell product for critical transduction and transfection steps
• Discover how ekko™ System for wash and concentrate processes throughout the cell therapy workflow achieve high cell recovery, viability, and effective residual removal
• Preview to ekko™ Select, our cell therapy selection platform, to achieve unmatched ease-of-use with direct processing from leukopaks reducing the need for preparation steps
Presented by:
Benjamin Ross-Johnsrud, Acoustic Technology Expert
Robert Scott, Mechanical Engineer III
How does the ICH Q5A revision impact viral safety strategies for biologics?MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3t7X9tg
How does the ICH Q5A revision impact viral safety strategies for biologics?
Biologics continue to grow at a fast pace. Manufactured using cell lines of human or animal origin, these are at risk of viral contamination making safety strategies critical. A comprehensive risk mitigation strategy using multiple orthogonal measures is a regulatory expectation. ICH Q5A, the globally-harmonized guideline outlines the expectations. ICH Q5A is currently being revised to address recent scientific advancements including novel therapeutic modalities, new manufacturing paradigms, updates in viral clearance applications, and alternate detection technologies. We’ll discuss the expected changes and potential impact on viral safety strategies with case studies and examples.
In this webinar, you will learn about:
• The Importance of virus testing in biologics products
• Regulatory landscape, expectations for the Q5A revision
• What's new and changing
• Examples of alternate testing schedules, impact on viral clearance
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Alison Armstrong, PhD, Sr. Director, Technical and Scientific Solutions
Improve Operational Efficiency by Over 30% with Product, Process, & Systems A...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3adaxWh
When implementing new automation systems, organizations must consider things like deployment time, user adoption, and costs.
They must also consider the cost of doing nothing – that is, what competitive advantage is lost in standing still? What time and quality is lost in repetitive, manual tasks rather than an automated, digital workflow? What operational efficiencies are lost?
In this webinar we examine how a product, process, and system agnostic automation platform can be deployed faster than traditional system specific software while bringing greater operational efficiencies (in many cases over 30% improvement).
To remain competitive in the market, biopharma manufacturers must adopt automation and digital technologies, but most plants still have island of automation consisting of independently functioning, standalone unit operations. This results in operational inefficiency, regulatory concerns, and a poor understanding of the process and product life cycle.
Taking the first, right step must include considering risks, costs, timelines, and technology alternatives. Traditional automation approaches tied to specific systems, processes, and products are, by their nature, limited; while an agnostic platform will address current biomanufacturing business challenges and ensure future readiness. With the right platform, a phased automation implementation can yield operational efficiency gains of up to 30% and improved product quality and regulatory compliance.
In this webinar, let's explore:
• Challenges of automation and digital technology adoption
• What a product, process, and system agnostic platform entails
• Applications and benefits of a process orchestration platform
• Ensuring future readiness with process orchestration
Presented by:
Braj Nandan Thakur, Global Product Manager - Automation
Insights from a Global Collaboration Accelerating Vaccine Development with an...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3Nbb5ug
Get insights and best practices from a multinational team establishing a platform for vaccine production. See how a long-term collaboration on a bench-scale process used to produce a Virus Like Particle (VLP) vaccine for SARS-CoV-2 was successfully converted to a robust GMP-compatible, scalable process.
The COVID-19 pandemic further emphasized the need for collaboration in the development of urgently needed vaccines and therapeutics. In this webinar, we take you behind the scenes of our collaboration with Technovax and Innovative Biotech in which a scalable VLP vaccine platform was optimized for use in a production facility in Nigeria in response to the need for local production of SARS-CoV-2 vaccines. The flexibility and robustness of the platform will enable its rapid deployment to support the West African pandemic readiness program. Initial development of the VLP process began in late 2019 and by March 2020, was already adapted for production of a SARS-CoV-2 vaccine.
In this webinar, you will learn:
• About building a priceless collaborative network with integrated solutions
• Virus-Like Particle Vaccines
• Process Development Overview and Challenges
• Pre-clinical Results and Next Steps
Presented by:
Jose M. Galarza, PhD,
President and Founder of TechnoVax
Naomi Baer,
Business development consultant, Emerging Biotech, BioProcess division
Youssef Gaabouri, Eng. ,
Associate Director, Head of Sales Middle East & Africa, BioProcess division
Risk-Based Qualification of X-Ray Sterilization for Single-Use SystemsMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3vQf0qv
In the single-use bioprocess industry, X-ray irradiation warrants consideration as an alternate sterilization technology. Using a risk-based qualification testing strategy is important when evaluating and implementing equivalent ionizing irradiation sterilization methods.
The urgent need for life-saving therapies as a result of the global pandemic has reinforced the criticality of flexibility in pharmaceutical manufacturing, including sterilization. The single-use bioprocess industry traditionally has employed gamma irradiation sterilization. X-ray irradiation is being considered as an additional sterilization technology for business and supply continuity. We will share a risk-based qualification testing strategy including Extractables and data generated to support comparability of gamma irradiation and X-ray irradiation as equivalent ionizing irradiation sterilization methods.
In this webinar, you will learn about:
• The comparison of gamma and X-ray irradiation sterilization
• A risk-based qualification test strategy
• Data evaluation of gamma versus X-ray sterilized single-use components
Presented by:
Monica Cardona,
Global Senior Program Manager
Paul Killian, Ph.D.,
R&D Director, Analytical Technologies
Rapid Replication Competent Adenovirus (rRCA) Detection: Accelerate your Lot ...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3MJ4u9V
Testing for presence of replication competent adenovirus (RCA) is a key component to ensure patient safety and a requirement for all biologicals manufactured using adenoviral vectors. For many adenoviral-based products, the RCA assay is a rate-limiting assay for lot release.
Join this webinar to learn about a rapid RCA detection assay currently in development, which combines a 7-day culture assay with a highly sensitive molecular endpoint specific for RCA. The method can detect presence of as little as 1 RCA in adenoviral vector material at an approximate concentration of 5x107 - 2x108 vector particles (VP)/mL, making it a suitable method to meet regulatory requirements while accelerating your lot release timelines.
In this webinar, you will learn about:
• Regulatory framework for adenoviral vector products
• Considerations for lot release testing of adenoviral-based therapies
• Advantages of a rapid method for RCA testing on production lot material
Presented by:
Axel Fun, Ph.D.,
Principal Scientist
Alberto Santana, MBA,
Product Manager, Biologics Biosafety Testing
The High Intensity Sweeteners Neotame and Sucralose: 2 Ways to ace the Patien...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3vQyN7K
Bitter medicines are an important issue, especially for pediatric applications. As several APIs have bitter tasting components, high intensity sweeteners for taste optimization are of great interest. Join our webinar to discover our new sweetener toolbox enabling safe and stable formulations.
Mask bitter aftertaste for a sweeter pill to swallow! Patients’ compliance and the therapeutic benefit are supported by a pleasant taste of pharmaceutical formulations. With the high intensity sweeteners Neotame and Sucralose, you have efficient tools at hand which are superior to other sweeteners in many aspects:
• excellent sugar-like taste profile
• outstanding sweetness factors
• use effectiveness
• enhanced stability
We will present our new toolbox of two high performance sweeteners and focus on aspects of stability, safety, the application in various dosage forms, and market perception.
In this webinar, you will learn:
• How to optimize the patients' taste experience of your pharmaceuticals
• How sweeteners can be differentiated by their sensory profiles and features
• How our new product offering Neotame can be effectively used in your targeted formulations
Presented by:
Almut von der Brelie,
Senior Manager Strategic Marketing, Excipients for Solid Applications
The Developability Classification System (DCS): Enabling an Optimized Approac...MilliporeSigma
This whitepaper by Dr. Daniel Joseph Price outlines how poorly soluble drug formulations can be designed using the developability classification system (DCS).
The DCS identifies the root cause of low solubility and enables lean, cost-effective and effective formulations to be developed.
#solubility #pharmaceuticalmanufacturing #oralsoliddosage #drugdevelopment
How to Accelerate and Enhance ADC TherapiesMilliporeSigma
In this webinar, you will learn about:
The advantages of using advanced intermediates to develop ADC therapies
How to increase ADC solubility and efficiency
Fast, small-scale ADC library generation
Seamless supply chain with reduced complexity and regulatory support
The ADCore product line offers versatile intermediates that simplify the synthesis of common ADC payloads (dolastatins, maytansinoids, and PBDs) by greatly reducing the number of synthetic steps. This translates to savings in development and manufacturing costs and shorter timelines to the clinic. To address the poor solubility of many ADC payloads, ChetoSensar™ was developed to significantly increase the hydrophilicity of the drug linker, which has been shown to also substantially increase the efficacy of ADCs and broaden the therapeutic window.
Lastly, the ADC Express™ service leverages conjugation chemistry and analytical expertise to help design and quickly synthesize sets of potential ADC therapies suitable for screening to simplify candidate selection and get ADC therapies to market faster.
ICH Guidelines for Pharmacovigilance.pdfNEHA GUPTA
The "ICH Guidelines for Pharmacovigilance" PDF provides a comprehensive overview of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines related to pharmacovigilance. These guidelines aim to ensure that drugs are safe and effective for patients by monitoring and assessing adverse effects, ensuring proper reporting systems, and improving risk management practices. The document is essential for professionals in the pharmaceutical industry, regulatory authorities, and healthcare providers, offering detailed procedures and standards for pharmacovigilance activities to enhance drug safety and protect public health.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
The Importance of Community Nursing Care.pdfAD Healthcare
NDIS and Community 24/7 Nursing Care is a specific type of support that may be provided under the NDIS for individuals with complex medical needs who require ongoing nursing care in a community setting, such as their home or a supported accommodation facility.
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
Artificial Intelligence to Optimize Cardiovascular Therapy
Amorphous formulations for bioavailability enhancement risks and opportunities by Daniel Joseph Price
1. The life science business of Merck KGaA,
Darmstadt, Germany operates as
MilliporeSigma in the U.S. and Canada.
Amorphous Formulation for
Bioavailability Enhancement
Challenges and Risks
Daniel Joseph Price
Strategic Marketing Manager, A&F
April 6th,2021
2. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada
5. Overview
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
Advanced Drug Delivery
Solid Formulation
Liquid Formulation
mRNA
API grade raw materials
Chemiflex Critical Raw Material
Program
cGMP/Non-GMP small molecules
Antibody-Drug Conjugate
(ADC)
cGMP small molecules-API
Generics-API
High potent API (HPAPI)
Linker (activated PEG)
Contract Manufacturing Formulation API / Pharm Materials
Actives and Formulaton
5
8. Poorly soluble drugs are on the increase
18
22
54
6
40
21
33
6 Class I
Class III
Class II
Class IV
New molecular entities (“NMEs”) are products containing active moieties that have not been approved by FDA previously.
Data adapted from Benet et al. JPharmSci. 2013;102(1):34-42
Distribution of oral
immediate-release drugs
on the market
NME percentages from
a data set of 28,912
medicinal chemistry
compounds
Today
Tomorrow
Good solubility
Poor solubility
Poor solubility can lead to low and variable absorption
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
8
9. Absorption is mainly related to solubility and permeability
• Type of dosage form
• Disintegration time
• Administration route
• Permeation enhancers
• API lipophilicity
• Efflux (P-gp)
• API stability
Speed up
liberation
Influence
distribution
Reduce
metabolism
Postpone
elimination
• Chemical approaches
• Physical approaches
• Tissue targeting
• Protein binding
• Avoid the first pass
effect
• Reduce enzymatic
bio-transformation
• Increase circulation
lifetime
• Increase size
Solubility Permeability Other
Increase
absorption
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
9
10. • Type of dosage form
• Disintegration time
• Administration route
• Permeation enhancers
• API lipophilicity
• Efflux (P-gp)
• API stability
Chemical
approaches
Physical
approaches
• Salt formation
• Prodrug formation
• Particle size reduction
• Complexation
• Drug carriers
• Solid form modification
• Solid dispersion
Speed up
liberation
Influence
distribution
Reduce
metabolism
Postpone
elimination
• Tissue targeting
• Protein binding
• Avoid the first pass
effect
• Reduce enzymatic
bio-transformation
• Increase circulation
lifetime
• Increase size
Permeability Other
Increase
absorption
Solubility
Solubility can be enhanced via chemical or physical
approaches
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
10
11. • Type of dosage form
• Disintegration time
• Administration route
• Permeation enhancers
• API lipophilicity
• Efflux (P-gp)
• API stability
Chemical
approaches
Physical
approaches
• Salt formation
• Prodrug formation
• Particle size reduction
• Complexation
• Drug carriers
• Solid form modification
• Solid dispersion
Speed up
liberation
Influence
distribution
Reduce
metabolism
Postpone
elimination
• Tissue targeting
• Protein binding
• Avoid the first pass
effect
• Reduce enzymatic
bio-transformation
• Increase circulation
lifetime
• Increase size
Permeability Other
Increase
absorption
Solubility
Solid state modification can substantially enhance drug
solubility
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
11
13. The most common amorphous formulation are polymeric
amorphous solid dispersions
Ditzinger, F. and Price, DJ. JPP. 2019
Polymer
Drug
Melt and Extrude
Spray-dry
Spray-dried
dispersion
(SDD)
Hot Melt
Extrusion
(HME)
How can we predict if our drug will be unstable?
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
13
14. Propensity for re-crystallization can be determined with the
Glass Forming ability (GFA) classification system
“The ease of vitrification of a liquid upon cooling” (Avramov et al. 2003)
GFA I GFA II GFA III
Baird et al.
Recrystallization
after cooling of
the melt
Recrystallization
after reheating the
cooled melt
No
recrystallization
Usage in marketed
ASDs
6.25 % 18.75 % 75.00 %
Poor glass formers (GFA-I) have a higher propensity for re-crystallization.
They are more fragile in the amorphous form.
Baird, et al. J Pharm Sci. 2010 and Wyttenbach and Kuentz. EJPB. 2017
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
14
15. Agenda
A&F Overview
Solubility and Amorphous Formulations
Mesoporous Silica, the Basics
Mesoporous Silica for Poor Glass Formers
Summary
16. Mesoporous silica inorganic drug carrier
Chemical formula: SiO2
Pharmacopoeial monograph: Silicon Dioxide (USP) and Silica, colloidal hydrated (Ph Eur)
Regulatory status: Generally Regarded As Safe (GRAS)
Typical values
Particle size 5 – 20 µm
Bulk density 0.32 g/mL (0.56 g/mL**)
Surface area ~ 500 m2/g
Pore size ~ 6 nm (disordered)
* By the U.S Food and Drug Administration
** Parteck® SLC loaded with 30% Ibuprofen. Density is increased upon loading with API
Parteck® SLC is an inorganic silica carrier
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
16
17. Solubilise
+Parteck SLC®
+ H2O
ca.6nm diameter
✓ Improved Solubility
✓ Increased Dissolution
✓ Improved Absorption
+ precipitation
inhibitor to prevent
recrystallisation
Sterically stabilized
Amorphous!
Solvent
Removal
Parteck® SLC is a porous SiO2 with up to 500 m2/g surface area
Parteck® SLC stabilizes the amorphous form via pore
adsorption and nanoconfinement
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
17
18. Development scale
1 / 13 kg loadings
Suitable equipment for loading
and drying available in different
sizes
Small scale
1 / 10 / 200 g loadings
Simple lab equipment which
can be easily adapted in scale
size
Production scale
100 kg loading
Process is transferred to
production scale without
further need for process
development
Loading is feasible from lab to production-scale
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
18
19. Fenofibrate is present in its amorphous state when loaded upon Parteck® SLC
Excipient.
DSC
Crystalline API
Parteck® SLC
Excipient,
API load 30 %
Wet Impregnation
Loading solvent: acetone
Method: wetness impregnation
Drug load: 30%
Amorphous
Residual solvent below ICH limit (0.5 %)
Lab-scale loading is accessible and requires no
extra capital investment
Loading of Fenofibrate onto Parteck® SLC Stabilizes the
Amorphous Form
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
19
20. Sample Composition
Capsule
Fenofibrate loaded onto Parteck® SLC Excipient
Blended with HPMC-AS (12.5 %)
Filled in capsules
Suspension
Fenofibrate loaded onto Parteck® SLC Excipient
blended with 12.5 % HPMC-AS
suspended in water
Reference Crystalline Fenofibrate blended with 12.5 % HPMC-AS
Study Description
In-vitro dissolution test
Dissolution tests were carried out in 500 mL FaSSIF in USP type II
dissolution apparatus (n=3)
In-vivo studies
Bioavailability studies were conducted in fasted, male Landrace pigs
(12.5 – 16 kg, n=6)
Reference: J. P. O'Shea1 , A. Wieber2 , C. Saal2 , B. Griffin1 , V. Witt2 , K. Nagarsekar3 , E. Herbert3,
J. Dressman3, D. Lubda2: Mesoporous Silica for Improving Oral Bioavailability of Fenofibrate:
In Vivo Evaluation, AAPS Poster 2016
1University College Cork, 2Merck KGaA, Darmstadt, Germany, 3Goethe University1
A Biorelevant in vitro dissolution and in vivo PK study in
pigs was carried out: suspension and capsules
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
20
21. Biorelevant dissolution provides a good prediction of relative bioavailability
PK study in pigs indicates a significant bioavailability enhancement of
Fenofibrate through Parteck® SLC Excipient also in vivo
0
500
1000
1500
2000
2500
3000
3500
4000
0 5 10 15 20 25
Plasma
concentration
(ng/ml)
Time (hrs)
Silica
Reference
Suspension
n = 6
Biorelevant in-vitro dissolution In-vivo bioavailability in fasted pigs
0
20
40
60
80
100
0 30 60 90 120
Dissolution
[%]
Time [min]
Reference Capsule
Silica Suspension
Silica Capsule
n = 3
Formulation of Fenofibrate with Parteck® SLC Enhances in
vivo bioavailability
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
21
22. Agenda
A&F Overview
Solubility and Amorphous Formulations
Mesoporous Silica, the Basics
Mesoporous Silica for Poor Glass Formers
Summary
23. Mesoporous silica is attractive from a physical chemistry
perspective for stabilization
GFA I GFA II GFA III
Baird et al.
Recrystallization
after cooling of
the melt
Recrystallization
after reheating
the cooled melt
No
recrystallization
Usage in
marketed ASDs
6.25 % 18.75 % 75.00 %
How can mesoporous silica be used to stabilize the previously impossible?
ca.6nm diameter
Sterically stabilized
Amorphous!
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
23
24. Dielectric spectroscopy has been used to study the effects of pore confinement
1 2a
Mesoporous silica has high potential for stabilization of poor glass formers!
Menthol mobility was probed by dielectric relaxation
spectroscopy, which allowed to identify two relaxation
processes in both pore sizes: a faster one associated with
mobility of neat-like menthol molecules (α-process),
and a slower, dominant one due to the hindered
mobility of menthol molecules adsorbed at the inner
pore walls (S-process).
• Menthol
• Tg: -60 °C
• Extremely poor glass former
• Stable amorphous with silica
• HME? SDD?
Molecular mobility is significantly hindered inside
mesoporous silica
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
24
25. • Optimized pharma-grade polymer for HME
• Silica impregnation loading method
• Characterization with XRPD and non-sink FaSSIF dissolution
• ICH Q1 A (R2) accelerated stability conditions (40 °C and 75% RH)
Two model poorly soluble poor glass formers were
formulated with mesoporous silica and HME
Price, DJ. And Ditzinger, F. Pharmaceutics. 2019.
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
25
26. Mesoporous silica is able to consistently stabilize high drug
loads of poor glass formers in the amorphous form
Loading Content 30% 20% 15% 7.5%
Carbamazepine HME
Carbamazepine Silica
Haloperidol HME
Haloperidol Silica
Success of solid-state conversion after loading or extruding with silica or
HME, respectively at set loading concentrations.
Price, DJ. And Ditzinger, F. Pharmaceutics. 2019.
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
26
27. Macroscopic changes in HME extrudates were observed after
only one-week under accelerated conditions
Macroscopic Changes in HME were observed after just one week under ICH
Q1 stability conditions
Price, DJ. And Ditzinger, F. Pharmaceutics. 2019.
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
27
28. SEM confirmed that phase separation was occurring in the extrudates
SEM images: Haloperidol loaded silica
(a) and HME (b) showing particle size and
morphology at 0 days (top) and 7 days
stability (bottom)
Price, DJ. And Ditzinger, F. Pharmaceutics. 2019.
SEM provides evidence for microscopic phase separation
in HME (1)
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
28
29. SEM provides evidence for microscopic phase separation
in HME (2)
SEM confirmed that phase separation was occurring in the extrudates
SEM images: Carbamazepine loaded
silica (a) and HME (b) showing particle
size and morphology at 0 days (top) and
7 days stability (bottom)
Price, DJ. And Ditzinger, F. Pharmaceutics. 2019.
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
29
30. Mesoporous silica remains amorphous for the duration of the
study, while HME re-crystallizes (1)
Instability in HME formulations would result in failure of the formulation
Haloperidol Loaded Silica Haloperidol HME
(a)= crystalline, (b)-(e) = fresh, 30, 60 and 90 day ICH Q1
Price, DJ. And Ditzinger, F. Pharmaceutics. 2019.
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
30
31. Instability in HME formulations would result in failure of the formulation
Carbamazepine Loaded Silica Carbamazepine HME
(a)= crystalline, (b)-(e) = fresh, 30, 60 and 90 day ICH Q1
Price, DJ. And Ditzinger, F. Pharmaceutics. 2019.
Mesoporous silica remains amorphous for the duration of the
study, while HME re-crystallizes (2)
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
31
33. Agenda
A&F Overview
Solubility and Amorphous Formulations
Mesoporous Silica, the Basics
Mesoporous Silica for Poor Glass Formers
Summary
34. Mesoporous can be used as a best-in-class excipient to
stabilize even the most poorly stable glass formers
Amorphous Stability is a key issue for development of poorly soluble drug
formulations.
Glass Forming Ability is a key physicochemical parameter that can predict
long-term amorphous stability.
Poor Glass Formers are unstable in the amorphous form and are difficult
to formulate with traditional amorphous technology. Resulting in a
disproportionate amount of good glass formers in amorphous formulations.
Parteck SLC® mesoporous silica can successfully stabilize poor glass
formers in the amorphous form.
4
Amorphous Formulation for Bioavailability Enhancement Challenges and Risks
34
3
2
1