-
Solid Form Studies
Center for Pharma Crystallization, J-STAR Research Inc 6 Cedar Drive, Cranbury, New Jersey 08512 Cure the pains caused by polymorphs, working with The Center for Pharma Crystallization (CfPC) at J-STAR Research. Discover more about our approach Aligned to drug development needs Bridging prediction & experimental data Cost effective & timely Data and science driven Our experienced, technically rigorous and client centric team, that has already helped select over 500 lead solid forms for small molecule candidates, is here to help your drug development programs. -
Center for Pharma Crystallization
J-STAR Research Inc 6 Cedar Drive, Cranbury, New Jersey 08512 Are you facing challenges getting reliable single crystal structures of APIs or intermediate compounds? You can get professional help from our leading crystallization expert with decades of successful experiences from BMS and the Center for Pharma Crystallization (CfPC) at J-STAR Research. -
For a drug substance administered via oral route, it should possess adequately aqueous solubility before passes through the gastrointestinal tract to complete the absorption, and then enters the blood steams for the pharmacological actions. Hence the solubility of a drug substance is one of the most important physicochemical properties to determine the drug’s fate to be developed the drug product for clinical applications.
-
Oral solid dosage forms, mainly in the forms of tablets and capsules, still dominate the drug product market for their convenience to patients, not only for administration, but also safe and easy to compliance. In manufacturing of oral solid dosage forms, the flowability of active pharmaceutical ingredient (API), excipients used to formulate the API, and formulations play an important role, and should be assessed in the drug product development stage. Even in the simplest processing route, the final blends containing the drug substance and excipients should present appropriate flowability in order to be compressed into tablets or filled into capsule shells. Poor flowability can cause segregation and stratification, and bad feeding which will consequently result in some manufacturing issues such as weight variation and bad content uniformity.
-
Wet granulation, dry granulation and direct blending are the three most common granulation processes for solid dosage form production in the pharmaceutical industry for decades. However, each of the three mentioned process has its drawbacks, among which, the requirement of post-granulation operations is one of the major weakness.
-
Drug discovery is an exceedingly complex process. Discovering a new chemical entity is in itself a huge accomplishment, which is often possible only after almost two decades of hard experimental work as well as advanced simulation efforts. Therefore, the next stage of the process, determination of toxicity becomes even more crucial as most new chemical entities (NCE) are disqualified if the NCE shows a potential toxic effect, despite any possible therapeutic effect. Once the NCE is determined to be safe, the next goal is to ensure availability of the NCE at the site of action in vivo upon administration through an appropriate route. -
Yuriy A. Abramov
yuriy.abramov@xtalpi.com
XtalPi Inc, Cambridge MA, USA.
AbstractGiven challenges facing the pharmaceutical industry, an accelerated Drug Development greatly benefits from guidance provided by computational methods.1 This presentation will focus on computational support of the following important tasks related to the pharmaceutical crystallization. That includes derisking of the stable solid form selection of pharmaceutical API; in silico coformer screening for an API or intermediate cocrystallization; rational solvent selection for solid solvate desolvation; and in silico solvent screening for impurity purge via recrystallization.
-
Moisture-activated dry granulation (MADG) is an economical and novel granulation process which only requires minor amount of liquid (1-5%) to trigger the agglomeration of particles, uses the high shear granulator to spread out the moisture and then form uniform granules without subsequent drying or milling process, which can save the cycle time tremendously.
-
Lipid-based formulation is proven to be one of the effective approaches to enhance solubility of poorly soluble drugs. At J-STAR, our scientists are experienced in this solubilization method, and at the same time, applying it to liquid-filled capsules to simplify the process and stay away from the manufacturing issues of oral dosage forms.
-
Dr. William Glauser
XtalPi, Inc., USA
AbstractProblems associated with polymorphic instability and increasingly insoluble drug candidates represent white space to innovate novel forms and processing methods with better properties in the drug product. But the journey from identifying new solid forms to creating engineered particles with optimal formulation properties has often been too inefficient to realize this goal.
Industry-wide voice of customer studies have revealed several bottlenecks along the critical pathway and a multicriteria optimization problem similar to that in earlier discovery phases. These studies suggest solutions that enhance the integration of experiment and computation, which itself integrates both physics-based and AI-based approaches. It also requires integrating mechanical and processing considerations earlier into the form discovery/selection stage. This desiloization of effort will require—in many instances—creative partnerships among biopharma, commercial technology providers, and academia to achieve.
-
Structure Elucidation Brochure
structure-elucidation-brochure-1.pdf – 1.21 MBJ-STAR provides high quality scientific and technical ability in small molecule problem solving including impurity/degradant isolation and structure elucidation. We have over 85 years of cumulative expertise in NMR/MS data acquisition and interpretation and are equipped with state-of-the-art instrumentation typically seen only in Big Pharma. We achieve results through a unique blend of highly integrated scientists among many interdisciplinary branches (structure elucidation/chemistry/analytical) who work efficiently together to achieve results.
-
[restrict] Enhance Powder Flow Density and Flow By Dry Particle Coating
enhance-powder-flow-density-and-flow-by-dry-particle-coating.pdf – 9.93 MB Many active pharmaceutical ingredients (API) exhibit deficient bulk powder properties such as poor flowability, low bulk density, high cohesion, etc. These deficiencies may cause some major issues for the performance of downstream processing thus affect content uniformity in final product. One of the effective methods to improve powder flow and bulk density is via the dry powder coating. This study performed by J-star Research provides details on this dry coating technology.[/restrict] -
Many active pharmaceutical ingredients (API) exhibit deficient bulk powder properties such as poor flowability, low bulk density, high cohesion, etc. These deficiencies may cause some major issues for the performance of downstream processing including the blending, content uniformity, and tablet making.
One of the methods for the improvements of the bulk powder properties is via the dry powder coating. This study is providing this coating technology. -
Direct compression (DC) process is the preferred method for tablet production because it is both simple and energy saving. However, only a minority of active pharmaceutical ingredients (APIs) can be made into tablets by using DC because of the powder properties of most APIs which have low bulk density, low flowability, etc. (1); Hence, technologies need to be developed to improve these powder properties to make the production of tablets feasible through DC. The co-precipitation technology (CPT) described below has been proven and can be used for the enhancement of powder flowability and bulk density.
-
Roller Compaction is one of best processing methods to improve the flowability of API. Comparatively, direct compression which skips the granulation step is more cost- effective. Our enabling technique scan significantly improve the API particles flowability, make it possible to replace roller compaction process with direct compression process, and deliver quality products while simplifying the process.
-
Dr. Shanming Kuang
Center for Pharma Crystallization, J-STAR Research Inc
6 Cedar Drive, Cranbury, New Jersey 08512
shanming.kuang@jstar-research.comAbstract
Rational selection of solvents plays a critical role in solid form screening and production. On the one hand, a variety of solvents with different properties are chosen in form screening to maximize the screening space of searching for all potential solid forms because some solvents selectively favor the generation of a particular form as a result of crystallization kinetics. On the other hand, some solvents need to be avoided in crystallization process due to formation of solvates that result in issues in residue solvent control and/or form transformation. We will present a lesson learned from a case study in which the wrong solvent was selected, which created huge pain in the commercialization. Efforts including computational approach utilized to address this issue will also be discussed.
-
CfPC at J-STAR Research
Center for Pharma Crystallization, J-STAR Research Inc 6 Cedar Drive, Cranbury, New Jersey 08512 See how the Center for Pharma Crystallization (CfPC) at J-STAR Research is effectively supporting new drug development programs: https://www.jstar-research.com/contract-rd-services/crystallization-rd/ -
Drug Product Brochure
drug-product-brochure.pdf – 1.41 MBWith the ability to develop both Drug Substance (DS) and Drug product (DP) under the same umbrella, our team enjoys a synergism absent in most CROs. The ability to bridge the DS/DP interface is a major competitive advantage, and we are able to shorten development timeline and to improve ruggedness of the DP process.
Our technology platforms provide but are not limited to optimized API powder properties and improved aqueous dissolution as needed. We can effectively address issues affecting formulation early in Phase 1. This fundamental material knowledge forms the basis of our Quality by Design approach to improving Phase 2, Phase 3, and commercial processes.
-
Research studies show that the majority of API candidates in the development pipeline have a BCS Class II rating, which means those APIs need a solubilization strategy to promote the bioavailability to improve their chance of clinical success.
One commercially validated technique to improve the solubility of poorly-soluble APIs is to prepare them as amorphous solid dispersions (ASD). J-star Research Inc. has spray drying (SD), hot melt extrusion (HME) and co-processing in house to establish ASD technique. This case study is focused on the preparation and evaluation of one model ASD produced at J-STAR using Spry Drying.
-
[restrict] Advantages of Co-precipitation Technology (CPT) Part I: Enhancement in Particle Morphology and Flow
advantages-of-co-precipitation-technology-cpt-part-i-enhancement-in-particle-morphology-and-flow.pdf – 13.58 MB Direct compression (DC) process is the preferred method for tablet production because it is both simple and energy saving. However, only a minority of active pharmaceutical ingredients (APIs) can be made into tablets by using DC because of the powder properties of most APIs (low bulk density, low flowability, etc.). Hence, technologies that can improve these powder properties are essential for DC. [/restrict] -
Jian Wang
Center for Pharma Crystallization, J-STAR Research Inc
6 Cedar Drive, Cranbury, New Jersey 08512
AbstractDiverse crystallization challenges encountered by CfPC (Center for Pharma Crystallization) and our clients will be analyzed systematically to provide insights into main bottleneck problems in today’s drug development programs. The general approaches taken at CfPC to address such problems as well as opportunities for improvement will be discussed. Examples will be given to highlight how enabling technologies and synergetic partnerships played a critical role in providing timely solutions to great challenges.
-
Don Kientzler
Center for Pharma Crystallization, J-STAR Research Inc
6 Cedar Drive, Cranbury, New Jersey 08512Abstract
Controlled crystallization of an API in submicron size was enabled based on an accurate solubility profile and a growth inhibition property via semi-continuous processing, to meet special formulation requirements. This process was also challenged by isolation of nano-API crystals to meet the low specification of residual salt content. When residual salt becomes too low, crystal growth accelerates. Diafiltration using membranes was applied for salt removal in connection to outstream of a flow-through CSTR for generation of submicron crystals, to deliver product meeting the specifications of both crystal size and the residual salt content.
-
Crystallization technologies are bridges between drug substances (DS) and drug products (DP) enabling consistent and robust safety and efficacy profiles of small molecule based medicines. In an effort to fully utilize existing tools and develop better new method-logies for solving bottleneck problems in drug develop-ment, the Center for Pharma Crystallization (CfPC) at J-STAR Research launched its first annual conference, jointly with XtalPi.
-
Solid Form Studies
Center for Pharma Crystallization, J-STAR Research Inc 6 Cedar Drive, Cranbury, New Jersey 08512 Cure the pains caused by polymorphs, working with The Center for Pharma Crystallization (CfPC) at J-STAR Research. Discover more about our approach Aligned to drug development needs Bridging prediction & experimental data Cost effective & timely Data and science driven Our experienced, technically rigorous and client centric team, that has already helped select over 500 lead solid forms for small molecule candidates, is here to help your drug development programs. -
Center for Pharma Crystallization
J-STAR Research Inc 6 Cedar Drive, Cranbury, New Jersey 08512 Are you facing challenges getting reliable single crystal structures of APIs or intermediate compounds? You can get professional help from our leading crystallization expert with decades of successful experiences from BMS and the Center for Pharma Crystallization (CfPC) at J-STAR Research. -
For a drug substance administered via oral route, it should possess adequately aqueous solubility before passes through the gastrointestinal tract to complete the absorption, and then enters the blood steams for the pharmacological actions. Hence the solubility of a drug substance is one of the most important physicochemical properties to determine the drug’s fate to be developed the drug product for clinical applications.
-
Oral solid dosage forms, mainly in the forms of tablets and capsules, still dominate the drug product market for their convenience to patients, not only for administration, but also safe and easy to compliance. In manufacturing of oral solid dosage forms, the flowability of active pharmaceutical ingredient (API), excipients used to formulate the API, and formulations play an important role, and should be assessed in the drug product development stage. Even in the simplest processing route, the final blends containing the drug substance and excipients should present appropriate flowability in order to be compressed into tablets or filled into capsule shells. Poor flowability can cause segregation and stratification, and bad feeding which will consequently result in some manufacturing issues such as weight variation and bad content uniformity.
-
Wet granulation, dry granulation and direct blending are the three most common granulation processes for solid dosage form production in the pharmaceutical industry for decades. However, each of the three mentioned process has its drawbacks, among which, the requirement of post-granulation operations is one of the major weakness.
-
Drug discovery is an exceedingly complex process. Discovering a new chemical entity is in itself a huge accomplishment, which is often possible only after almost two decades of hard experimental work as well as advanced simulation efforts. Therefore, the next stage of the process, determination of toxicity becomes even more crucial as most new chemical entities (NCE) are disqualified if the NCE shows a potential toxic effect, despite any possible therapeutic effect. Once the NCE is determined to be safe, the next goal is to ensure availability of the NCE at the site of action in vivo upon administration through an appropriate route. -
Yuriy A. Abramov
yuriy.abramov@xtalpi.com
XtalPi Inc, Cambridge MA, USA.
AbstractGiven challenges facing the pharmaceutical industry, an accelerated Drug Development greatly benefits from guidance provided by computational methods.1 This presentation will focus on computational support of the following important tasks related to the pharmaceutical crystallization. That includes derisking of the stable solid form selection of pharmaceutical API; in silico coformer screening for an API or intermediate cocrystallization; rational solvent selection for solid solvate desolvation; and in silico solvent screening for impurity purge via recrystallization.
-
Moisture-activated dry granulation (MADG) is an economical and novel granulation process which only requires minor amount of liquid (1-5%) to trigger the agglomeration of particles, uses the high shear granulator to spread out the moisture and then form uniform granules without subsequent drying or milling process, which can save the cycle time tremendously.
-
Lipid-based formulation is proven to be one of the effective approaches to enhance solubility of poorly soluble drugs. At J-STAR, our scientists are experienced in this solubilization method, and at the same time, applying it to liquid-filled capsules to simplify the process and stay away from the manufacturing issues of oral dosage forms.
-
Dr. William Glauser
XtalPi, Inc., USA
AbstractProblems associated with polymorphic instability and increasingly insoluble drug candidates represent white space to innovate novel forms and processing methods with better properties in the drug product. But the journey from identifying new solid forms to creating engineered particles with optimal formulation properties has often been too inefficient to realize this goal.
Industry-wide voice of customer studies have revealed several bottlenecks along the critical pathway and a multicriteria optimization problem similar to that in earlier discovery phases. These studies suggest solutions that enhance the integration of experiment and computation, which itself integrates both physics-based and AI-based approaches. It also requires integrating mechanical and processing considerations earlier into the form discovery/selection stage. This desiloization of effort will require—in many instances—creative partnerships among biopharma, commercial technology providers, and academia to achieve.
-
Structure Elucidation Brochure
structure-elucidation-brochure-1.pdf – 1.21 MBJ-STAR provides high quality scientific and technical ability in small molecule problem solving including impurity/degradant isolation and structure elucidation. We have over 85 years of cumulative expertise in NMR/MS data acquisition and interpretation and are equipped with state-of-the-art instrumentation typically seen only in Big Pharma. We achieve results through a unique blend of highly integrated scientists among many interdisciplinary branches (structure elucidation/chemistry/analytical) who work efficiently together to achieve results.
-
[restrict] Enhance Powder Flow Density and Flow By Dry Particle Coating
enhance-powder-flow-density-and-flow-by-dry-particle-coating.pdf – 9.93 MB Many active pharmaceutical ingredients (API) exhibit deficient bulk powder properties such as poor flowability, low bulk density, high cohesion, etc. These deficiencies may cause some major issues for the performance of downstream processing thus affect content uniformity in final product. One of the effective methods to improve powder flow and bulk density is via the dry powder coating. This study performed by J-star Research provides details on this dry coating technology.[/restrict] -
Many active pharmaceutical ingredients (API) exhibit deficient bulk powder properties such as poor flowability, low bulk density, high cohesion, etc. These deficiencies may cause some major issues for the performance of downstream processing including the blending, content uniformity, and tablet making.
One of the methods for the improvements of the bulk powder properties is via the dry powder coating. This study is providing this coating technology. -
Direct compression (DC) process is the preferred method for tablet production because it is both simple and energy saving. However, only a minority of active pharmaceutical ingredients (APIs) can be made into tablets by using DC because of the powder properties of most APIs which have low bulk density, low flowability, etc. (1); Hence, technologies need to be developed to improve these powder properties to make the production of tablets feasible through DC. The co-precipitation technology (CPT) described below has been proven and can be used for the enhancement of powder flowability and bulk density.
-
Roller Compaction is one of best processing methods to improve the flowability of API. Comparatively, direct compression which skips the granulation step is more cost- effective. Our enabling technique scan significantly improve the API particles flowability, make it possible to replace roller compaction process with direct compression process, and deliver quality products while simplifying the process.
-
Dr. Shanming Kuang
Center for Pharma Crystallization, J-STAR Research Inc
6 Cedar Drive, Cranbury, New Jersey 08512
shanming.kuang@jstar-research.comAbstract
Rational selection of solvents plays a critical role in solid form screening and production. On the one hand, a variety of solvents with different properties are chosen in form screening to maximize the screening space of searching for all potential solid forms because some solvents selectively favor the generation of a particular form as a result of crystallization kinetics. On the other hand, some solvents need to be avoided in crystallization process due to formation of solvates that result in issues in residue solvent control and/or form transformation. We will present a lesson learned from a case study in which the wrong solvent was selected, which created huge pain in the commercialization. Efforts including computational approach utilized to address this issue will also be discussed.
-
CfPC at J-STAR Research
Center for Pharma Crystallization, J-STAR Research Inc 6 Cedar Drive, Cranbury, New Jersey 08512 See how the Center for Pharma Crystallization (CfPC) at J-STAR Research is effectively supporting new drug development programs: https://www.jstar-research.com/contract-rd-services/crystallization-rd/ -
Drug Product Brochure
drug-product-brochure.pdf – 1.41 MBWith the ability to develop both Drug Substance (DS) and Drug product (DP) under the same umbrella, our team enjoys a synergism absent in most CROs. The ability to bridge the DS/DP interface is a major competitive advantage, and we are able to shorten development timeline and to improve ruggedness of the DP process.
Our technology platforms provide but are not limited to optimized API powder properties and improved aqueous dissolution as needed. We can effectively address issues affecting formulation early in Phase 1. This fundamental material knowledge forms the basis of our Quality by Design approach to improving Phase 2, Phase 3, and commercial processes.
-
Research studies show that the majority of API candidates in the development pipeline have a BCS Class II rating, which means those APIs need a solubilization strategy to promote the bioavailability to improve their chance of clinical success.
One commercially validated technique to improve the solubility of poorly-soluble APIs is to prepare them as amorphous solid dispersions (ASD). J-star Research Inc. has spray drying (SD), hot melt extrusion (HME) and co-processing in house to establish ASD technique. This case study is focused on the preparation and evaluation of one model ASD produced at J-STAR using Spry Drying.
-
[restrict] Advantages of Co-precipitation Technology (CPT) Part I: Enhancement in Particle Morphology and Flow
advantages-of-co-precipitation-technology-cpt-part-i-enhancement-in-particle-morphology-and-flow.pdf – 13.58 MB Direct compression (DC) process is the preferred method for tablet production because it is both simple and energy saving. However, only a minority of active pharmaceutical ingredients (APIs) can be made into tablets by using DC because of the powder properties of most APIs (low bulk density, low flowability, etc.). Hence, technologies that can improve these powder properties are essential for DC. [/restrict] -
Jian Wang
Center for Pharma Crystallization, J-STAR Research Inc
6 Cedar Drive, Cranbury, New Jersey 08512
AbstractDiverse crystallization challenges encountered by CfPC (Center for Pharma Crystallization) and our clients will be analyzed systematically to provide insights into main bottleneck problems in today’s drug development programs. The general approaches taken at CfPC to address such problems as well as opportunities for improvement will be discussed. Examples will be given to highlight how enabling technologies and synergetic partnerships played a critical role in providing timely solutions to great challenges.
-
Don Kientzler
Center for Pharma Crystallization, J-STAR Research Inc
6 Cedar Drive, Cranbury, New Jersey 08512Abstract
Controlled crystallization of an API in submicron size was enabled based on an accurate solubility profile and a growth inhibition property via semi-continuous processing, to meet special formulation requirements. This process was also challenged by isolation of nano-API crystals to meet the low specification of residual salt content. When residual salt becomes too low, crystal growth accelerates. Diafiltration using membranes was applied for salt removal in connection to outstream of a flow-through CSTR for generation of submicron crystals, to deliver product meeting the specifications of both crystal size and the residual salt content.
-
Crystallization technologies are bridges between drug substances (DS) and drug products (DP) enabling consistent and robust safety and efficacy profiles of small molecule based medicines. In an effort to fully utilize existing tools and develop better new method-logies for solving bottleneck problems in drug develop-ment, the Center for Pharma Crystallization (CfPC) at J-STAR Research launched its first annual conference, jointly with XtalPi.