Scale-Up Considerations for Orally Inhaled Drug Products

2019 ◽  
pp. 233-248
Author(s):  
Jeremy Clarke ◽  
S. van den Ban
Keyword(s):  
Scale Up ◽  
Drug Products ◽  
Orally Inhaled Drug Products

scholarly journals Innovating on Inhaled Bioequivalence: A Critical Analysis of the Current Limitations, Potential Solutions and Stakeholders of the Process

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1051
Author(s):  
Jonattan Gallegos-Catalán ◽  
Zachary Warnken ◽  
Tania F. Bahamondez-Canas ◽  
Daniel Moraga-Espinoza
Keyword(s):  
New Technologies ◽  
Innovation Process ◽  
Cost Effective ◽  
Regulatory Agencies ◽  
Drug Products ◽  
Effective Strategies ◽  
Rate Analysis ◽  
Orally Inhaled Drug Products ◽  
Next Generation Impactor ◽  
First Time

Orally inhaled drug products (OIDPs) are an important group of medicines traditionally used to treat pulmonary diseases. Over the past decade, this trend has broadened, increasing their use in other conditions such as diabetes, expanding the interest in this administration route. Thus, the bioequivalence of OIDPs is more important than ever, aiming to increase access to affordable, safe and effective medicines, which translates into better public health policies. However, regulatory agencies leading the bioequivalence process are still deciding the best approach for ensuring a proposed inhalable product is bioequivalent. This lack of agreement translates into less cost-effective strategies to determine bioequivalence, discouraging innovation in this field. The Next-Generation Impactor (NGI) is an example of the slow pace at which the inhalation field evolves. The NGI was officially implemented in 2003, being the last equipment innovation for OIDP characterization. Even though it was a breakthrough in the field, it did not solve other deficiencies of the BE process such as dissolution rate analysis on physiologically relevant conditions, being the last attempt of transferring technology into the field. This review aims to reveal the steps required for innovation in the regulations defining the bioequivalence of OIDPs, elucidating the pitfalls of implementing new technologies in the current standards. To do so, we collected the opinion of experts from the literature to explain these trends, showing, for the first time, the stakeholders of the OIDP market. This review analyzes the stakeholders involved in the development, improvement and implementation of methodologies that can help assess bioequivalence between OIDPs. Additionally, it presents a list of methods potentially useful to overcome some of the current limitations of the bioequivalence standard methodologies. Finally, we review one of the most revolutionary approaches, the inhaled Biopharmaceutical Classification System (IBCs), which can help establish priorities and order in both the innovation process and in regulations for OIDPs.

scholarly journals Use of PBPK Modeling To Evaluate the Performance of DissolvIt, a Biorelevant Dissolution Assay for Orally Inhaled Drug Products

2019 ◽  
Vol 16 (3) ◽  
pp. 1245-1254 ◽  
Author(s):  
Mireille Hassoun ◽  
Maria Malmlöf ◽  
Otto Scheibelhofer ◽  
Abhinav Kumar ◽  
Sukhi Bansal ◽  
...  
Keyword(s):  
Pbpk Modeling ◽  
Drug Products ◽  
Biorelevant Dissolution ◽  
Orally Inhaled Drug Products

Establishing bioequivalence for orally inhaled drug products

2011 ◽  
Vol 8 (11) ◽  
pp. 1531-1532 ◽  
Author(s):  
Peter T Daley-Yates ◽  
David A Parkins
Keyword(s):  
Drug Products ◽  
Orally Inhaled Drug Products

scholarly journals Improved Quality Control Metrics for Cascade Impaction Measurements of Orally Inhaled Drug Products (OIPs)

2009 ◽  
Vol 10 (4) ◽  
pp. 1276-1285 ◽  
Author(s):  
Terrence P. Tougas ◽  
David Christopher ◽  
Jolyon P. Mitchell ◽  
Helen Strickland ◽  
Bruce Wyka ◽  
...  
Keyword(s):  
Quality Control ◽  
Drug Products ◽  
Quality Control Metrics ◽  
Orally Inhaled Drug Products ◽  
Cascade Impaction

scholarly journals Optimization of the Transwell® System for Assessing the Dissolution Behavior of Orally Inhaled Drug Products through In Vitro and In Silico Approaches

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1109
Author(s):  
Elham Amini ◽  
Abhinav Kurumaddali ◽  
Sharvari Bhagwat ◽  
Simon M. Berger ◽  
Günther Hochhaus
Keyword(s):  
In Silico ◽  
Mass Effect ◽  
Dissolution Behavior ◽  
Experimental Conditions ◽  
Drug Products ◽  
Starting Point ◽  
Orally Inhaled Drug Products ◽  
Model Drug ◽  
The Impact

The aim of this study was to further evaluate and optimize the Transwell® system for assessing the dissolution behavior of orally inhaled drug products (OIDPs), using fluticasone propionate as a model drug. Sample preparation involved the collection of a relevant inhalable dose fraction through an anatomical mouth/throat model, resulting in a more uniform presentation of drug particles during the subsequent dissolution test. The method differed from previously published procedures by (1) using a 0.4 µm polycarbonate (PC) membrane, (2) stirring the receptor compartment, and (3) placing the drug-containing side of the filter paper face downwards, towards the PC membrane. A model developed in silico, paired with the results of in vitro studies, suggested that a dissolution medium providing a solubility of about 5 µg/mL would be a good starting point for the method’s development, resulting in mean transfer times that were about 10 times longer than those of a solution. Furthermore, the model suggested that larger donor/receptor and sampling volumes (3, 3.3 and 2 mL, respectively) will significantly reduce the so-called “mass effect”. The outcomes of this study shed further light on the impact of experimental conditions on the complex interplay of dissolution and diffusion within a volume-limited system, under non-sink conditions.

scholarly journals Evaluation of Excipient Risk in BCS Class I and III Biowaivers

2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Melissa Metry ◽  
James E. Polli
Keyword(s):  
Drug Product ◽  
Scale Up ◽  
Drug Formulation ◽  
Product Regulatory ◽  
Drug Bioavailability ◽  
Drug Products ◽  
Fda Guidance ◽  
Regulatory Guidance

AbstractThe objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the use of excipients in drug products for decades, considerable research efforts have been directed towards evaluating their potential effects on drug bioavailability. Potential excipient concerns stem from drug formulation changes (e.g., scale-up and post-approval changes, development of a new generic product). Regulatory agencies have established in vivo bioequivalence standards and, as a result, may waive the in vivo requirement, known as a biowaiver, for some oral products. Biowaiver acceptance criteria are based on the in vitro characterization of the drug substance and drug product using the Biopharmaceutics Classification System (BCS). Various regulatory guidance documents have been issued regarding BCS-based biowaivers, such that the current FDA guidance is more restrictive than prior guidance, specifically about excipient risk. In particular, sugar alcohols have been identified as potential absorption-modifying excipients. These biowaivers and excipient risks are discussed here.

scholarly journals Model-Based Scale-up Methodologies for Pharmaceutical Granulation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 453
Author(s):  
Eun Ha Jang ◽  
Yun Sang Park ◽  
Min-Soo Kim ◽  
Du Hyung Choi
Keyword(s):  
Pharmaceutical Industry ◽  
Process Parameters ◽  
Drug Product ◽  
Scale Up ◽  
Quality Attributes ◽  
Modeling Method ◽  
Drug Products ◽  
Model Based ◽  
Process Strategy

In the pharmaceutical industry, it is a major challenge to maintain consistent quality of drug products when the batch scale of a process is changed from a laboratory scale to a pilot or commercial scale. Generally, a pharmaceutical manufacturing process involves various unit operations, such as blending, granulation, milling, tableting and coating and the process parameters of a unit operation have significant effects on the quality of the drug product. Depending on the change in batch scale, various process parameters should be strategically controlled to ensure consistent quality attributes of a drug product. In particular, the granulation may be significantly influenced by scale variation as a result of changes in various process parameters and equipment geometry. In this study, model-based scale-up methodologies for pharmaceutical granulation are presented, along with data from various related reports. The first is an engineering-based modeling method that uses dimensionless numbers based on process similarity. The second is a process analytical technology-based modeling method that maintains the desired quality attributes through flexible adjustment of process parameters by monitoring the quality attributes of process products in real time. The third is a physics-based modeling method that involves a process simulation that understands and predicts drug quality through calculation of the behavior of the process using physics related to the process. The applications of these three scale-up methods are summarized according to granulation mechanisms, such as wet granulation and dry granulation. This review shows that these model-based scale-up methodologies provide a systematic process strategy that can ensure the quality of drug products in the pharmaceutical industry.

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