83
Volume 5, Issue 10: Special Issue
(EJAR)
ISSN: 2181-2020
MPHAPP
THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL
CONFERENCE
“
MODERN PHARMACEUTICS: ACTUAL
PROBLEMS AND PROSPECTS
”
TASHKENT, OCTOBER 17, 2025
in-academy.uz
IMMUNOSUPPRESSIVE DRUGS: SCIENTIFIC PRINCIPLES OF DEVELOPING
COMBINATION DOSAGE FORMS
Toyirova M.J.
1
Yunusova Kh.M.
2
Tashkent Pharmaceutical Institute, Tashkent city, Republic of Uzbekistan
https://doi.org/10.5281/zenodo.17321486
Relevance:
Immunosuppressant drugs are among the key therapeutic groups in modern
transplantology and the treatment of autoimmune diseases. These agents suppress the immune
response by inhibiting lymphocyte proliferation, limiting cytokine synthesis, or blocking intracellular
signaling pathways. As a result, they prevent graft rejection and alleviate the course of chronic
autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and
psoriasis.
However, the use of immunosuppressants as monotherapy in clinical practice is associated with
a number of challenges: administration at high doses often leads to severe adverse effects, including
nephrotoxicity, hepatotoxicity, hematological disorders, and metabolic syndrome; long-term use of
certain agents increases susceptibility to infections; pharmacokinetic variability (e.g., reduced
absorption when taken with food, genetic differences in metabolism) directly affects therapeutic
efficacy.
To address these issues in clinical practice, various immunosuppressants are prescribed in
combination. For example, tacrolimus + mycophenolate mofetil, cyclosporine + azathioprine, and
tacrolimus + everolimus are commonly used combinations. Nevertheless, the simultaneous
administration of several drugs is inconvenient for patients, reduces treatment adherence, and
complicates the monitoring of drug–drug interactions. Therefore, the development of fixed-dose
combination dosage forms — such as tablets or capsules containing multiple active substances —
represents a highly relevant direction in pharmaceutical technology.
Materials and methods:
The study included literature analysis, generalization of clinical
practice data, and comparative assessment of pharmaceutical technologies. The main manufacturing
methods of combination tablets (wet granulation, dry granulation, direct compression) were
evaluated. The physicochemical compatibility of active substances, their interaction with excipients,
solubility, and disintegration properties were studied. Critical quality attributes such as dose
uniformity, mechanical strength, dissolution, and disintegration were comprehensively assessed.
Results:
The research led to the following scientific and practical conclusions:
Pharmacodynamic synergy - the combination of immunosuppressants acting through different
mechanisms (for example, mycophenolate mofetil, a purine synthesis inhibitor, and tacrolimus, a
calcineurin inhibitor) allows achieving higher clinical efficacy at lower doses. Reduction of adverse
effects - in combination forms, the dose of active substances is reduced, which significantly decreases
the incidence of nephrotoxicity, hematological disorders, and infectious complications.
Pharmacokinetic stability - a fixed-dose formulation harmonizes the rate and duration of drug
absorption, maintaining stable plasma concentrations without sharp fluctuations. Clinical
convenience - a single combination tablet simplifies the administration process for patients, improves
adherence to therapy, and strengthens treatment effectiveness. Technological opportunities - in the
development of combination forms, wet granulation was evaluated as the most optimal method, as it
84
Volume 5, Issue 10: Special Issue
(EJAR)
ISSN: 2181-2020
MPHAPP
THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL
CONFERENCE
“
MODERN PHARMACEUTICS: ACTUAL
PROBLEMS AND PROSPECTS
”
TASHKENT, OCTOBER 17, 2025
in-academy.uz
ensures uniform distribution of substances, while coating technologies provide the possibility to
regulate the release rate of active ingredients.
Conclusions:
The development of combination immunosuppressive dosage forms is a
promising approach to improve the treatment of transplantation and autoimmune diseases. Such
formulations can increase therapeutic efficacy, minimize adverse effects, and enhance patients’
quality of life. In this context, creating a combination tablet based on mycophenolate mofetil
constitutes a highly relevant scientific and practical task for both the pharmaceutical industry and the
healthcare system.
