scholarly journals The solid-state continuum: a perspective on the interrelationships between different solid-state forms in drug substance and drug product

2014 ◽  
Vol 67 (6) ◽  
pp. 757-772 ◽  
Author(s):  
David P. Elder ◽  
James E. Patterson ◽  
René Holm
Keyword(s):  
Solid State ◽  
Drug Product ◽  
Drug Substance

scholarly journals The investigation of polymorph transition of erlotinib salts

2016 ◽  
Author(s):  
Wioleta Maruszak ◽  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Wojciech Łuniewski ◽  
Krzysztof Bańkowski ◽  
...  
Keyword(s):  
Solid State ◽  
Kinase Inhibitor ◽  
Drug Product ◽  
Variable Temperature ◽  
Drug Substance ◽  
Crystalline Solid ◽  
Scanning Calorimetry ◽  
Thermal Methods ◽  
Polymorphic Transitions ◽  
Polymorphic Forms

Erlotinib is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR) and is used to treat non-small cell lung cancer (NSCLC), pancreatic cancer and several other types of cancer [1]. It is known that erlotinib forms different salts which can exist in multiple crystalline solid forms. This important property known as a polymorphism may have an impact on physical and chemical stability of the drug substance (API), processability during manufacturing in the final drug product and bioavailability of the drug to the patient. Changes in the crystal structure of API can lead to the undesired changes in properties. Hence, the control of the polymorphic form is essential during the drug substance manufacture and requires a thorough understanding of solid-state changes that may occur in pharmaceutical materials. To achieve a comprehensive understanding of solid-state transformations different analytical techniques are applied. In our studies the variable–temperature powder X-ray diffraction (VT–PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transformed infrared (FTIR), attenuated total reflectance (ATR) and Raman spectroscopy were used to investigate the correlation between the thermal behavior and structural transformations of polymorphic forms of erlotinib salts. VT-PXRD method has detected the temperature range of the existence of polymorphic transitions, spectroscopy methods have characterized intramolecular vibrations and thermal methods have provided information on the transition and melting temperature and relationships between polymorphic forms.

scholarly journals The investigation of polymorph transition of erlotinib salts

2016 ◽  
Author(s):  
Wioleta Maruszak ◽  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Wojciech Łuniewski ◽  
Krzysztof Bańkowski ◽  
...  
Keyword(s):  
Solid State ◽  
Kinase Inhibitor ◽  
Drug Product ◽  
Variable Temperature ◽  
Drug Substance ◽  
Crystalline Solid ◽  
Scanning Calorimetry ◽  
Thermal Methods ◽  
Polymorphic Transitions ◽  
Polymorphic Forms

Erlotinib is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR) and is used to treat non-small cell lung cancer (NSCLC), pancreatic cancer and several other types of cancer [1]. It is known that erlotinib forms different salts which can exist in multiple crystalline solid forms. This important property known as a polymorphism may have an impact on physical and chemical stability of the drug substance (API), processability during manufacturing in the final drug product and bioavailability of the drug to the patient. Changes in the crystal structure of API can lead to the undesired changes in properties. Hence, the control of the polymorphic form is essential during the drug substance manufacture and requires a thorough understanding of solid-state changes that may occur in pharmaceutical materials. To achieve a comprehensive understanding of solid-state transformations different analytical techniques are applied. In our studies the variable–temperature powder X-ray diffraction (VT–PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transformed infrared (FTIR), attenuated total reflectance (ATR) and Raman spectroscopy were used to investigate the correlation between the thermal behavior and structural transformations of polymorphic forms of erlotinib salts. VT-PXRD method has detected the temperature range of the existence of polymorphic transitions, spectroscopy methods have characterized intramolecular vibrations and thermal methods have provided information on the transition and melting temperature and relationships between polymorphic forms.

scholarly journals Understanding and Kinetic Modeling of Complex Degradation Pathways in the Solid Dosage Form: The Case of Saxagliptin

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 452 ◽  
Author(s):  
Robnik ◽  
Likozar ◽  
Wang ◽  
Stanić Ljubin ◽  
Časar
Keyword(s):  
Relative Humidity ◽  
Degradation Product ◽  
Degradation Products ◽  
Drug Product ◽  
Degradation Kinetics ◽  
Dosage Forms ◽  
Drug Substance ◽  
Polymer Composition ◽  
Solid Dosage Forms ◽  
Solid Dosage

Drug substance degradation kinetics in solid dosage forms is rarely mechanistically modeled due to several potential micro-environmental and manufacturing related effects that need to be integrated into rate laws. The aim of our work was to construct a model capable of predicting individual degradation product concentrations, taking into account also formulation composition parameters. A comprehensive study was done on active film-coated tablets, manufactured by layering of the drug substance, a primary amine compound saxagliptin, onto inert tablet cores. Formulation variables like polyethylene glycol (PEG) 6000 amount and film-coat polymer composition are incorporated into the model, and are connected to saxagliptin degradation, via formation of reactive impurities. Derived reaction equations are based on mechanisms supported by ab initio calculations of individual reaction activation energies. Alongside temperature, relative humidity, and reactant concentration, the drug substance impurity profile is dependent on micro-environmental pH, altered by formation of acidic PEG degradation products. A consequence of pH lowering, due to formation of formic acid, is lower formation of main saxagliptin degradation product epi-cyclic amidine, a better resistance of formulation to high relative humidity conditions, and satisfactory tablet appearance. Discovered insights enhance the understanding of degradational behavior of similarly composed solid dosage forms on overall drug product quality and may be adopted by pharmaceutical scientists for the design of a stable formulation.

Microscopy in Pharmaceutical Development

1998 ◽  
Vol 4 (S2) ◽  
pp. 478-479
Author(s):  
R. A. Carlton
Keyword(s):  
Solid State ◽  
Polarized Light ◽  
Particle Size Analysis ◽  
Primary Objective ◽  
Drug Substance ◽  
Size Analysis ◽  
Pharmaceutical Development ◽  
Drug Candidates ◽  
Infrared Microspectroscopy ◽  
The Face

Many different microscopic techniques are utilized in the development of new pharmaceuticals. For that reason, pharmaceutical companies have supported microscopy and microscopists even in the face of retrenchments in many other industries. Microscopy has the following three major uses in pharmaceutical development: 1) solid-state characterization of drug substance; 2) particle size analysis; 3) contaminant identification. Microscopy is also an important component of the study of the biological activity of drugs but that subject will not be discussed here.The analysis of the solid-state properties of new drug candidates is probably the most important and challenging subject of study for pharmaceutical microscopists.1 The primary objective of these studies is identification of the most suitable solid-state form (i.e. polymorph, solvate, hydrate) of the drug substance for development. Polarized light microscopy (PLM), thermal microscopy (TM), infrared microspectroscopy (IR), and Raman microspectroscopy (RM) are all utilized in these studies. Both PLM and TM are used to discover new polymorphs and solvates of the chemical.

Justification of Drug Product Dissolution Rate and Drug Substance Particle Size Specifications Based on Absorption PBPK Modeling for Lesinurad Immediate Release Tablets

2016 ◽  
Vol 13 (9) ◽  
pp. 3256-3269 ◽  
Author(s):  
Xavier J. H. Pepin ◽  
Talia R. Flanagan ◽  
David J. Holt ◽  
Anna Eidelman ◽  
Don Treacy ◽  
...  
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Drug Product ◽  
Immediate Release ◽  
Drug Substance ◽  
Pbpk Modeling

Application of high throughput technologies to drug substance and drug product development

2004 ◽  
Vol 28 (6-7) ◽  
pp. 943-953 ◽  
Author(s):  
Colin R Gardner ◽  
Orn Almarsson ◽  
Hongming Chen ◽  
Sherry Morissette ◽  
Matt Peterson ◽  
...  
Keyword(s):  
Product Development ◽  
High Throughput ◽  
Drug Product ◽  
Drug Substance
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