“…However, the formulation containing such excipients needs additional characterization tests to investigate the functionality of the dosage form. Regulatory agencies are also keen to review information about the toxicity of these novel specialized excipients [ 78 ]. Fig.…”
There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients’ quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as “Safe and Effective” products. However, the underlying challenges involved in the development, scalability, and characterization of these injectable products are critical. Moreover, the guidelines available do not provide a clear understanding of these complex products, making it difficult to anticipate the regulatory requirements. Thus, it becomes imperative to comprehend the criticalities and develop an understanding of these products. This review discusses various complexities involved in the parenteral products such as complex drug substances, excipients, dosage forms, drug administration devices like pre-filled syringes and injector pens, and its different characterization tools and techniques. The review also provides a brief discussion on the regulatory aspects and associated hurdles with other parenteral products.
Graphical abstract
“…However, the formulation containing such excipients needs additional characterization tests to investigate the functionality of the dosage form. Regulatory agencies are also keen to review information about the toxicity of these novel specialized excipients [ 78 ]. Fig.…”
There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients’ quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as “Safe and Effective” products. However, the underlying challenges involved in the development, scalability, and characterization of these injectable products are critical. Moreover, the guidelines available do not provide a clear understanding of these complex products, making it difficult to anticipate the regulatory requirements. Thus, it becomes imperative to comprehend the criticalities and develop an understanding of these products. This review discusses various complexities involved in the parenteral products such as complex drug substances, excipients, dosage forms, drug administration devices like pre-filled syringes and injector pens, and its different characterization tools and techniques. The review also provides a brief discussion on the regulatory aspects and associated hurdles with other parenteral products.
Graphical abstract
“…It is vital to recognize that GRAS status is given to the context of use of an excipient, not the ingredient itself. The regulatory authorities recognize the need for novel excipients as indispensable in development of new medicines that require advanced drug delivery systems [ 170 , 171 ]. However, they also have a responsibility to ensure that any novel excipient is safe and can provide consistent performance.…”
Section: Novel Asd Polymer Considerations and Challengementioning
confidence: 99%
“…Europe is the exception to this rule where currently a novel excipient can only be introduced as part of the drug product marketing authorization. This means the sponsor of a molecule using the excipient in their formulation is required to submit the application [ 170 ]. FDA Center for Drug Evaluation and Research is exploring a pilot program for the toxicological and quality evaluation of novel excipients so that it is not necessary for the novel excipient to be included in a finished drug product described in an IND, NDA or a BLA [ 171 ].…”
Section: Novel Asd Polymer Considerations and Challengementioning
Poorly water-soluble drugs pose a significant challenge to developability due to poor oral absorption leading to poor bioavailability. Several approaches exist that improve the oral absorption of such compounds by enhancing the aqueous solubility and/or dissolution rate of the drug. These include chemical modifications such as salts, co-crystals or prodrugs and physical modifications such as complexation, nanocrystals or conversion to amorphous form. Among these formulation strategies, the conversion to amorphous form has been successfully deployed across the pharmaceutical industry, accounting for approximately 30% of the marketed products that require solubility enhancement and making it the most frequently used technology from 2000 to 2020. This article discusses the underlying scientific theory and influence of the active compound, the material properties and manufacturing processes on the selection and design of amorphous solid dispersion (ASD) products as marketed products. Recent advances in the analytical tools to characterize ASDs stability and ability to be processed into suitable, patient-centric dosage forms are also described. The unmet need and regulatory path for the development of novel ASD polymers is finally discussed, including a description of the experimental data that can be used to establish if a new polymer offers sufficient differentiation from the established polymers to warrant advancement.
“…Compounding the challenge is the fact that drug makers hesitate to include novel excipients in their products. A study in 2018 found that among drugs listed in the European Public Assessment Report only a few products contain novel excipients (17). This is understandable.…”
Section: Challenges With Excipient Innovationmentioning
confidence: 99%
“…Drug products containing novel excipients take a longer time to gain regulatory approval, additional years in some cases. Worse, issues associated with novel excipients, such as a lack of safety data in humans, might cause the drug applications to be rejected (17). Also, makers of generic drugs are disincentivized to use novel excipients because drug products that contain novel excipients are ineligible for the ANDA pathway (5).…”
Section: Challenges With Excipient Innovationmentioning
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
