Application of the quality by design approach in the pharmaceutical development of 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-f]xanthine tablets

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Introduction. 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine is a promising agent for enhancing the liver's detoxifying function by inducing the cytochrome P450 system. In the pharmaceutical development of a new drug based on it, the use of a systematic Quality-by-Design approach becomes relevant, which includes the definition of the target quality profile, critical process and material parameters, as well as quality attributes of the finished product.

The aim of the study is to determine critical quality attributes and process parameters within the framework of the Quality-by-Design approach in the pharmaceutical development of a finished dosage form of a new inducer of the hepatocyte monooxygenase system - 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine.

Material and methods. The object of the study is the technology of obtaining 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine tablets by wet granulation. The method of constructing Ishikawa diagrams and Failure Mode and Effects Analysis were used to determine the critical process parameters and quality attributes of the finished product.

Results. Critical quality attributes of tablets (uniformity of dosing, disintegration, crushing strength), materials (loss-on-drying of lactose monohydrate, microcrystalline cellulose, microbiological purity of the materials, related impurities of the 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine), critical process parameters (size of granules, their drying mode, volume and concentration of the binding solution and control of residual moisture) were determined.

Conclusion. Critical parameters and attributes of the technology and the finished product have been established. Sections 5 and 9 of the pilot industrial regulations for the production of 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine tablets have been substantiated.

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作者简介

A. Petrakov

Siberian State Medical University

编辑信件的主要联系方式.
Email: aipp19@yandex.ru
ORCID iD: 0009-0001-9625-0498
SPIN 代码: 2931-1280

Laboratory Research Assistant of the Scientific and Educational Laboratory of Chemical and Pharmaceutical Research

俄罗斯联邦, 2, Moscow tract, Tomsk, 634050

S. Krivoshchekov

Siberian State Medical University

Email: ksv_tsu@mail.ru
ORCID iD: 0000-0001-5505-7141
SPIN 代码: 1064-5950

Ph.D. (Chem.), Associate Professor of the Department of pharmaceutical chemistry, Head of the Quality Control Laboratory of the Central Research Laboratory

俄罗斯联邦, 2, Moscow tract, Tomsk, 634050

A. Guryev

Siberian State Medical University

Email: titan-m@mail.ru
ORCID iD: 0000-0002-1120-4979
SPIN 代码: 3731-4439

Dr.Sc. (Pharm.), Head of the Center for Implementation of Technologies of the Central Research Laboratory

俄罗斯联邦, 2, Moscow tract, Tomsk, 634050

M. Belousov

Siberian State Medical University

Email: mvb63@mail.ru
ORCID iD: 0000-0002-2153-7945
SPIN 代码: 8185-8117

Dr.Sc. (Pharm.), Professor, Head of the Department of Pharmaceutical Chemistry

俄罗斯联邦, 2, Moscow tract, Tomsk, 634050

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2. Fig. 1. Ishikawa diagram. Determination of critical quality attributes of tablets

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3. Fig. 2. Factors Affecting the Quality of DPDTX Tablets

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4. Fig. 3. Histograms of distribution of quality attributes of DPDTX tablets

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