Preformulation and Formulation during Drug Development

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 5984

Special Issue Editor


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Guest Editor
College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 339700, Korea
Interests: preformulation; salt; polymorphism; pulmonary drug delivery system; solubility; phase transition

Special Issue Information

Dear Colleagues,

It is well known that approximately 50% of drug candidates going to clinical trials fail primarily due to efficacy and safety issues. The rest may drop due to solubility, drug–drug interaction, and stability issues. In this sense, preformulation and formulation are key factors improving the rate of success during drug development by improving the physicochemical properties as well as pharmacokinetic properties. In addition, preformulation and formulation play important roles in developing incrementally modified drugs by manipulating physicochemical properties or pharmacokinetic properties of drugs or applying various drug delivery systems. With advances in pharmaceutical technology, in many cases, those issues are not a problem anymore. However, it is still challenging to modify the properties as desired.

In this Special Issue, recent advances in improving and modifying the properties of drugs by applying the knowledge of preformulation and formulation will be discussed.

Prof. Dr. Eun Hee Lee
Guest Editor

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Keywords

  • preformulation
  • formulation
  • design of experiment
  • drug delivery system
  • solubility

Published Papers (2 papers)

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Research

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19 pages, 2161 KiB  
Article
Development of Nafamostat Mesylate Immediate-Release Tablet by Drug Repositioning Using Quality-by-Design Approach
by Hyeon-A Kim and Joo-Eun Kim
Pharmaceutics 2022, 14(6), 1219; https://doi.org/10.3390/pharmaceutics14061219 - 08 Jun 2022
Cited by 3 | Viewed by 2375
Abstract
We aimed to develop nafamostat mesylate immediate-release tablets for the treatment of COVID-19 through drug repositioning studies of nafamostat mesylate injection. Nafamostat mesylate is a serine protease inhibitor known to inhibit the activity of the transmembrane protease, serine 2 enzyme that affects the [...] Read more.
We aimed to develop nafamostat mesylate immediate-release tablets for the treatment of COVID-19 through drug repositioning studies of nafamostat mesylate injection. Nafamostat mesylate is a serine protease inhibitor known to inhibit the activity of the transmembrane protease, serine 2 enzyme that affects the penetration of the COVID-19 virus, thereby preventing the binding of the angiotensin-converting enzyme 2 receptor in vivo and the spike protein of the COVID-19 virus. The formulation was selected through a stability study after manufacturing by a wet granulation process and a direct tableting process to develop a stable nafamostat mesylate immediate-release tablet. Formulation issues for the selected processes were addressed using the design of experiments and quality-by-design approaches. The dissolution rate of the developed tablet was confirmed to be >90% within 30 min in the four major dissolutions, except in the pH 6.8 dissolution medium. Additionally, an in vivo pharmacokinetic study was performed in monkeys, and the pharmacokinetic profiles of nafamostat injections, oral solutions, and tablets were compared. The half-life during oral administration was confirmed to be significantly longer than the reported literature value of 8 min, and the bioavailability of the tablet was approximately 25% higher than that of the oral solution. Full article
(This article belongs to the Special Issue Preformulation and Formulation during Drug Development)
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32 pages, 4515 KiB  
Review
Finite Element Analysis and Modeling in Pharmaceutical Tableting
by Ioannis Partheniadis, Vasiliki Terzi and Ioannis Nikolakakis
Pharmaceutics 2022, 14(3), 673; https://doi.org/10.3390/pharmaceutics14030673 - 18 Mar 2022
Cited by 5 | Viewed by 2721
Abstract
Finite element analysis (FEA) is a computational method providing numerical solutions and mathematical modeling of complex physical phenomena that evolve during compression tableting of pharmaceutical powders. Since the early 2000s, FEA has been utilized together with various constitutive material models in a quest [...] Read more.
Finite element analysis (FEA) is a computational method providing numerical solutions and mathematical modeling of complex physical phenomena that evolve during compression tableting of pharmaceutical powders. Since the early 2000s, FEA has been utilized together with various constitutive material models in a quest for a deeper understanding and unraveling of the complex mechanisms that govern powder compression. The objective of the present review paper is to highlight the potential and feasibility of FEA for implementation in pharmaceutical tableting in order to elucidate important aspects of the process, namely: stress and density distributions, temperature evolution, effect of punch shape on tablet formation, effect of friction, and failure of the tablet under stress. The constitutive models and theoretical background governing the above aspects of tablet compression and tablet fracture under diametral loading are also presented. In the last sections, applications of FEA in pharmaceutical tableting are demonstrated by many examples that prove its utilization and point out further potential applications. Full article
(This article belongs to the Special Issue Preformulation and Formulation during Drug Development)
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