Impact of the Polymorphic Form of Drugs/<scp>NCE</scp>s on Preformulation and Formulation Development

Alsirawan, Mhd. Bashir; Paradkar, Anant

doi:10.1002/9783527812172.ch1

Cited by 5 publications

(7 citation statements)

References 121 publications

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“…All of this demonstrates that the results obtained at the pilot scale were corroborated at an industrial scale for all tested sources of API. The differences observed in the critical material attributes studied proved that each of the sources exhibited different physical properties, which may lead to a different impact on the processability of the drug product [ 53 , 54 ]. Although all sources are chemically identical and complied with the chemical test specifications described in the certificate of analysis, they showed dissimilar physical behavior that may affect the manufacturing process and critical quality attributes of the drug product [ 15 , 55 ].…”

Section: Resultsmentioning

confidence: 99%

SeDeM as a Tool to Validate Drug Substance Manufacturing Processes and Assess Scalability and Suitability for Direct Compression: Supplier Screening

Figuera-Figuera,

Suñé-Pou,

Pérez-Lozano

et al. 2023

Pharmaceutics

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During the development of an oral solid form of a drug substance, a thorough understanding of the critical material attributes is necessary, as the physical properties of the active pharmaceutical ingredient (API) can profoundly influence the drug product’s manufacturability, critical quality attributes, and bioavailability. The objective of this study was to validate the manufacturing process of the drug Linezolid from three different sources at both the pilot and industrial scale and to identify differences in critical material attributes between the API manufacturers. Furthermore, the scalability factor between the pilot and industrial scale and the suitability of a process for direct compression were also evaluated. In the present study, the different sources of API were characterized by SeDeM methodology, particle size distribution, and scanning electron microscopy determinations. The statistical analysis revealed that no statistically significant differences were found for any of the parameters under study for the same API source analyzed on both scales. On the other hand, for most of the parameters evaluated, statistical differences were observed between the different sources. It was concluded that SeDeM was able to successfully validate the API manufacturing process, assess scalability, and distinguish between sources. Therefore, it could be highly valuable in the formulation phase to select the best API source.

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Section: Resultsmentioning

confidence: 99%

SeDeM as a Tool to Validate Drug Substance Manufacturing Processes and Assess Scalability and Suitability for Direct Compression: Supplier Screening

Figuera-Figuera,

Suñé-Pou,

Pérez-Lozano

et al. 2023

Pharmaceutics

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“…These forms contain a secondary heterostructure within the crystal lattice, with the same chemical makeup (examples are water, solvent, co-former, etc.). These forms are also known by other names like hydrates, solvates, and cocrystals, and FDA considered them polymorphs [50].…”

Section: Pseudo-polymorphismmentioning

confidence: 99%

Preformulation Studies: A Versatile Tool in Formulation Design

Ahirwar¹,

Shukla²

2023

Drug Formulation Design

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The physicochemical properties of pharmacological molecules have a tremendous effect on safety and efficacy. Poor physicochemical properties can often make it hard to set up a reliable structure-activity relationship (SAR) with no prominent efficacy in preclinical and clinical models. This can lead to more variability in capability and higher drug development costs in the entire development process, and in the worst case, even to stop the clinical trials in the later period. Understanding the basic physicochemical properties makes it possible to separate and untangle investigational observations hence poor molecular properties can be changed or fixed during the design phase. This makes it more likely that the molecule will make it through the long and difficult development process. The decline in innovator pharmacotherapeutics number registrations decline each year and the industry is under even more pressure than in the past to speed up the drug development process. This reduces the length of time required for development and introduces innovative pharmaceutical products. To do this, it is imperative to proceed with an organised approach and act appropriately the first time. The current chapter aims to focus on the important physicochemical properties of the selected molecule, along with how those properties are evaluated and implicated in both discovery enablement and final dosage form development.

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“…Meta-stable polymorphs are known to be vulnerable to the environmental and processing condition and undergo polymorphic transformation. It is reported that 85% of new chemical entities (NCEs) exhibit pseudopolymorphism and 50% having real polymorphism [7,8].…”

Section: Panda and Lankalapallimentioning

confidence: 99%

Bioavailability and Polymorphic Stability Challenges Affecting Drug Product’s Potential: A Critical Evaluation and Pertinent Solution

Panda,

LANKALAPALLI

2023

Asian J Pharm Clin Res

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Clinical failure remains an ongoing challenge in pharmaceutical drug product development. Solubility and permeability therefore play a very critical role in achieving desired bioavailability and pharmacological response, which in turns affects clinical safety and efficacy significantly. The situation becomes more critical when the drug candidate exhibits polymorphism and undergoes polymorphic transformation due to its meta-stable nature. This review article outlines the available technologies, pertinent regulations, the concepts involved in the enhancement of bioavailability and polymorphic stability to overcome the clinical failures. Various available technologies for bioavailability enhancement such as salification, micronization, complexation, microemulsification, nano emulsification, cocrystal formation, and amorphous solid dispersion with their advantage and disadvantage in formulating a stable drug product containing a polymorphic and meta-stable drug substance. Thermodynamic and kinetic aspects of polymorphic transformation are discussed to understand different excipient and process-induced transformation during manufacturing and shelf life of the drug product. Selecting the right instrument from the analytical toolbox is equally important to understand the diverse nature of polymorphic transformation. This review provides state-of-the-art information available on advanced analytical tools along with their capabilities, advantages, and disadvantage with respect to physical/structural analysis of polymorphs and polymorphic transformation.

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Impact of the Polymorphic Form of Drugs/NCEs on Preformulation and Formulation Development

Cited by 5 publications

References 121 publications

SeDeM as a Tool to Validate Drug Substance Manufacturing Processes and Assess Scalability and Suitability for Direct Compression: Supplier Screening

SeDeM as a Tool to Validate Drug Substance Manufacturing Processes and Assess Scalability and Suitability for Direct Compression: Supplier Screening

Preformulation Studies: A Versatile Tool in Formulation Design

Bioavailability and Polymorphic Stability Challenges Affecting Drug Product’s Potential: A Critical Evaluation and Pertinent Solution

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