Manufacturers across many sectors and industries have recognized that a successful product requires customer input and focus from start to finish. The pharmaceutical industry has previously dedicated its efforts and resources toward establishing the quality, safety, and stability of a novel drug, without enough consideration of the reception of the drug by the customer. For example, highly protective multi-layer blister packages might be developed to ensure the stability of the capsule inside, but the typical patient (75–80 years old) would be unable to open it by themselves. While the chemistry and efficacy of a new formulation are of the utmost importance, the drug is not going to be effective if the patient is unable or unwilling to adhere to their medication regimen.

The increased concern surrounding medical adherence, particularly in the context of antibiotic resistance, has initiated a significant shift toward patient-centricity. As patients begin to be placed at the forefront of pharmaceutical development, novel technologies and alternative formulations are emerging to facilitate greater patient compliance. Whether these technologies allow for reduced dosage frequency, fewer side effects, smaller pill size, or more convenient drug delivery routes, patient-centricity is increasingly at the core of the pharma industry.

Read this article in the Trends in Formulation 2022 eBook

Frédérique Bordes-Picard is vice-president of Business Development, Europe, at Nanoform.

When referring to this article, please cite it as F. Bordes-Picard, " Small is a Powerful Ingredient for Patient-Centric Formulations," 

Pharmaceutical Technology's Trends in Formulation

Articles

Development

Patient centricity is driving change in drug discovery and development, leading to a a new dawn in therapeutics.

Small is a Powerful Ingredient for Patient-Centric Formulations

Time-to-market remains a significant factor in drug development today, as delays in timelines can often have costly and damaging effects, not only to the drug developer but to the patient. Challenges in the drug development cycle arise early in the drug candidate screening process. In this article, Industry players discuss how technological innovation and advances in analytical approaches enhance early drug candidate screening workflows to help shorten drug discovery and development timelines. 

Pharmaceutical Technology’s October 2022 Trends in Formulation 

When referring to this article, please cite it as F. Mirasol, “Using a Drug Candidate Screening Strategy to Mitigate Late-Stage Risk," 

Pharmaceutical Technology Trends in Formulation

An early drug candidate screening strategy should incorporate clear targets to lessen late-stage failure.

Using a Drug Candidate Screening Strategy to Mitigate Late-Stage Risk

Gene therapy has rapidly expanded conceptually and technically, now covering a wide array of tools and methods, including the advancement of viral vector delivery for gene therapies. Lentiviral vectors and adeno-associated virus (AAV) are two primary delivery mechanisms of gene therapies. While versatile and robust, there are some inherent weaknesses in the production of both AAV and lentivirus vectors, and, as a result, production is not well optimized. Over time, significant improvements have been developed to facilitate the manufacture of these viral vectors at each stage.

Pharmaceutical Technology’s October 2022 Trends in Formulation

Ger Brophy, is the executive vice-president of Biopharma Production, Arvind Srivastava is a technical fellow, Bioprocessing, and Greg Swan is business development manager for Cell & Gene Therapy; all are at Avantor.

, October 2022
October 2022
Pages: 36–40

When referring to this article, please cite it as G. Brophy, A. Srivastava, and G.Swan, “Addressing Developmental Challenges of Gene Therapy Viral Vectors," 

Manufacturing

Significant improvements have been developed to tackle the challenges in viral vector manufacturing at each stage.

Addressing Developmental Challenges of Gene Therapy Viral Vectors

There is a growing demand for biologics spurred by clinical success, favorable safety data, and the ability of biologics to target the underlying cause of disease. Progress in proteins, peptides, nucleic acids, vaccines, and monoclonal antibodies (mAbs) has allowed biologics to advance quickly, especially in recent years. According to an article in 

, 25% of new chemical entities approved by FDA between 2015 and 2019 were biologics (1). Perhaps the most striking recent example of the demand for biologics is the rapid scale-up and application of messenger RNA (mRNA) vaccines to treat COVID-19. Though progress has been swift, challenges have created barriers to global adoption due to complications related to formulation, thermostability, and drug delivery. 

Biologics originate from living organisms, have large molecular weights, and generally cannot be chemically synthesized. This means they are vulnerable to the environment and require extreme care to formulate, manufacture, and store (2). As biologics are large molecules with primary, secondary, tertiary, and quaternary structures, they are also sensitive and expensive to produce (3). While biologics are conventionally delivered intravenously in liquid form, liquid formulations exhibit chemical and physical stability problems. Conversely, biologics formulated as a dry powder are more stable and are less prone to degradation, but drug manufacturers must consider shelf stability as well as which excipients and formulation conditions will enable a longer shelf life. Additionally, the chemical and physical properties of the final product must be considered during formulation to fit the route of administration.

This article explores technological innovations that could overcome challenges in formulation and the delivery of biologics—especially for respiratory diseases where inhaled drug delivery offers a significant advantage—to address the need for scale-up of biologics to benefit a broad range of patients.

Read the full article in the Trends in Formulation 2022 eBook.

Robert O. Williams III, PhD, is the division head and professor of molecular pharmaceutics and drug delivery at The University of Texas at Austin, College of Pharmacy; the Johnson & Johnson centennial chair in pharmacy at the University of Texas at Austin, College of Pharmacy; editor-in-chief of the American Association of Pharmaceutical Scientists (AAPS) PharmSciTech scientific journal; and the technology inventor/special advisor, TFF Pharmaceuticals.


eBook: Trends in Formulation 2022
October 2022
Pages: 30–35

When referring to this article, please cite it as R. O. Williams III, "Improved Formulations to Enable Stable Delivery of Biologics," 

Formulation

How dry powder techniques can overcome limitations in biologics development and delivery to broaden routes of administration and global accessibility.

Improved Formulations to Enable Stable Delivery of Biologics

-nitroso compounds (Figure 1) are formed by the reaction of secondary and tertiary amines, amides, carbamates, urea, guanidine with nitrite or other nitrogenous agents (including N2O3 and N2O4). The carcinogenic properties of 

-nitrosamines, have been known for many years (1). Based on numerous studies, International Agency for Research on Cancer (IARC) has categorized 

-nitroso compounds in Class 2a and Class 2b, as probable and possible carcinogens, and International Council for Harmonisation (ICH) M7 has considered them as a “cohort of concern” (2). However, it needs to be remembered that 

-alkylurea, guanidine, carbamates are not in the same category as 

. They are direct acting mutagens that do not need metabolic activation to exhibit their mutagenicity or carcinogenicity as is the case of 

-nitrosamines. Thus, they should not be put in the same category as the 

-nitrosamines (3). The purpose of this paper is to discuss the differences in mechanism of activation of 

-nitrosamines and the fact that they should not be treated alike.

Aloka Srinivasan, PhD is a principal and managing partner of Raaha LLC. Chuck Lambert, PhD, DABT, ERT is principal toxicologist at Intrinsik Ltd.

When referring to this article, please cite it as A. Srinivasan and C. Lambert, " Nitrosamides–Should They Be Treated the Same as Nitrosamines?," 

Quality

The authors discuss the differences in mechanism of activation of N-nitrosamides versus N-nitrosamines and the fact that they should not be treated the same.

Nitrosamides–Should They Be Treated the Same as Nitrosamines?

Vitamin E TPGS, or d-α-tocopheryl polyethylene glycol 1000 succinate, was first developed more than 60 years ago as a water-soluble form of naturally occurring vitamin E. Originally used to treat vitamin E deficiency in cholestatic patients, TPGS quickly attracted attention as a versatile solubilizer due to its amphiphilic nature and surfactant properties. Further application of this molecule emerged in the 1990s, when TPGS was shown to improve epithelial absorption by modulating cellular efflux. Researchers have continued to find a variety of new and exciting applications of this molecule, and TPGS has become an important tool for drug delivery formulators. This report serves to summarize some of recent innovations using TPGS for improved delivery of bioactive materials.

Read this article in the Trends in Formulation ebook.

Greg Paddon-Jones, PhD, is director of Product Development at Antares Health Products.

When referring to this article, please cite it as G. Paddon-Jones, "Emerging Applications of Vitamin E TPGS in Drug Delivery," 

The author discusses some new applications of TPGS in the pharmaceutical field that should see this versatile excipient retain its place in the drug formulators toolbox.

Pharmaceutical Technology, Trends in Formulation, October 2022

Small is a Powerful Ingredient for Patient-Centric Formulations

Using a Drug Candidate Screening Strategy to Mitigate Late-Stage Risk

Addressing Developmental Challenges of Gene Therapy Viral Vectors

Improved Formulations to Enable Stable Delivery of Biologics

Nitrosamides–Should They Be Treated the Same as Nitrosamines?

Emerging Applications of Vitamin E TPGS in Drug Delivery