DSC purity analysis is based on thermodynamic phase diagrams for substances (purity ≥98%) which undergo a melting point. Impurities
which have eutectic behaviour with the analyte are determined together.
DSC purity analysis obtained from a single melting event of a 1–2 mg sample is, therefore, extremely attractive for the global
assessment of eutectic impurities. The main advantages in early development lie in the very small amount of material necessary
and the very fast analysis time.
However, the DSC purity analysis cannot replace chromatographic methods which deliver specific individual levels of impurities.
Furthermore, a complete validation of a DSC purity method is difficult and time consuming. Despite these limitations, DSC
is the best support for the development of chromatographic methods, for purity profile and stability assessment during pharmaceutical
Parameters of purity determination and validation aspects are discussed. Examples of use in pharmaceutical development are
Összefoglaló. A COVID–19-járvány egyre növekvő számú fertőzött
betegének ellátása érdekében rövid időn belül szükség mutatkozott vírusellenes
terápiás lehetőségekre. A gyors reagálás szempontját figyelembe véve erre a
célra elsősorban más vírusok ellen már kifejlesztett vírusellenes szerek
jöhetnek szóba. A magyar betegek ellátásbiztonsága szempontjából különösen
fontos a hatóanyagok és gyógyszerkészítmények hazai gyártása. Ezt a cél tűzte ki
a favipiravir, egy széles spektrumú antivirális hatóanyag hazai fejlesztése,
amely sikeresen befejeződött, a gyógyszerkészítmény klinikai vizsgálata
Summary. Increasing impact of COVID-19 on the healthcare system
prompted the identification of potential antiviral therapies. Due to the
immediate demand, known drugs were subjected to repositioning attempts. These
drugs include agents inhibiting the viral entry into the host cells, drugs
potentially blocking the release of the viral RNA from the endosomes, antivirals
inhibiting the replication of the viral RNA and finally compounds that might
prevent the assembly of the new virion. Since there is less experience with
camostat and nafamostat, the entry inhibitors tested in Japan, and due to the
ambiguous data collected with the endosome blocking chloroquine and
hydroxyl-chloroquine, we focused on the actual antiviral treatment options for
COVID-19 infections. In addition to favipiravir and remdesivir that were used
early, at the onset of the pandemic, we discuss novel candidates including
molnupiravir, a promising antiviral actually investigated in clinical trials.
Considering the needs of Hungarian COVID patients and the security of supply as
first priority, we selected favipiravir and developed a convenient process for
the industry-scale production of the active pharmaceutical ingredient (API). At
the end of this review we summarize the development and clinical investigation
of favipiravir, a wide spectrum antiviral drug used for the treatment of mild
and moderate COVID patients in Hungary in both ambulant and clinical settings.
The Hungarian COVID Task Force set up two consortia, one for the development and
the other for the clinical investigations of favipiravir. The objective of the
favipiravir development consortium was to develop processes for the production
of Favipiravir API and dosage forms. The consortium completed the pilot plant
scale industrial production of the API and produced clinical samples for the
upcoming trials. The selection and laboratory scale optimization of the
synthesis route was performed at the Medicinal Chemistry Research Group of the
Research Center for Natural Sciences. The laboratory scale synthesis was scaled
up for pilot plant production at EVI plc and Gedeon Richter plc. GMP production
was realized at the facilities of Gedeon Richter plc. Finished dosage forms were
developed at Meditop Ltd who produced the clinical samples under GMP conditions.
The clinical consortium is headed by the Hungarian section of the European
Clinical Research Infrastructure Network (ECRIN) and organized two trials. One
of these trials investigates favipiravir produced in Hungary while the other
trial is performed with favipiravir produced in Japan. Both studies were
approved by the Hungarian regulatory agency (OGYÉI) and are ongoing.
Authors:Chunhui Dai, David R. Snead, Ping Zhang, and Timothy F. Jamison
Flow chemistry has attracted significant interest in pharmaceutical development, where substantial efforts have been directed toward the design of continuous processes. Here, we report a total synthesis of atropine in flow that features an unusual hydroxymethylation and separation of several byproducts with high structural similarity to atropine. Using a combination of careful pH control in three sequential liquid—liquid extractions and a functionalized resin, atropine is delivered by the flow system with >98% purity.
Study of excipients incompatibility with drugs in an early phase of pharmaceutical development is still a persistent difficulty
within the pharmaceutical industry. We examine here the compatibility between an experimental drug (nebicapone) and common
excipients using differential scanning calorimetry (DSC), high sensitivity DSC (HSDSC) and a conventional heat stress test.
The results obtained indicate that nebicapone may be compatible with lactose monohydrate and sodium croscarmellose but is
incompatible with magnesium stearate. This study concludes that HSDSC, in stepwise isothermal mode, may be used as a potential
tool for detecting excipient incompatibilities.
Authors:Pintu B. Prajapati, Kunjan B. Bodiwala, and Shailesh A. Shah
registration of pharmaceuticals for human use, ICH Harmonized Tripartite Guideline, Geneva, 2003.
International Conference on Harmonization Tripartite Guideline “Q8, PharmaceuticalDevelopment”, Step 4 version, Geneva
Authors:Libby Yoerg, M. Ellen Matthews, Lakshmi Kaza, Naullage Indika Perera, David W. Ball, John Moran, and Alan T. Riga
is to differentiate the amorphous and crystalline content of three monosaccharides using thermal analytical methods. Amorphous materials are of increasing interest in pharmaceuticaldevelopment because they have more bioavailability and increased
Authors:A. Foppoli, L. Zema, A. Maroni, M. Sangalli, M. Caira, and A. Gazzaniga
at an early identification of all possible crystalline modifications, are nowadays a fundamental step in the pharmaceuticaldevelopment of new drugs and drug products [ 1 ].
Theophylline-7-acetic acid (1,2,3,6-tetrahydro-1,3-dimethyl-2
Authors:Gregory A. Price, Debasis Mallik, and Michael G. Organ
risks in pharmaceutical products originating from the manufacturing conditions. PAT-enabled tools are defined as tools that allow process understanding for scientific, risk-managed pharmaceuticaldevelopment, manufacture, and quality assurance. The