A model design for managing technological parameters at the stage of the pharmaceutical development of antidiabetic drugs in the form of solid dosage forms

Abstract

Aim. To develop a model for managing technological parameters at the stage of the pharmaceutical development of an antidiabetic drug in tablets with API of SGLT-2 class – a derivative of gliflozin.

Materials and methods. In the study conducted, the methods of system and comparative analysis, generalization, statistical processing and synthesis were used in determining the projected prospects, design, modeling, mathematical modeling, tabular and graphic means of presenting the results. To implement the goals and objectives of the study, software and electronic resources of the Anatomical Therapeutically Chemical Classification System (ATC), Biopharmaceutical Classification System (BCS), Compendium, State Register of Medicines of Ukraine were used; statistical data and data from clinical studies of the content were as follows: https://www.wipo.int; https://www.dec.gov.ua; https://www.clinicaltrials.gov; https://www.ncbi.nlm. nih.gov; https://eacpt.org; https://bpspubs.onlinelibrary.wiley.com. The study was conducted on the modern equipment for determining the bulk density (ERWEKA SVM 202, Germany), the flowability of powders (ERWEKA GT, Germany), resistance to crushing (ERWEKA TBH-525 WTO, Germany), friability (ERWEKA TAR 200, Germany), disintegration (ERWEKA ZT 33, Germany). The active ingredient in tablets of the antidiabetic drug is API calculated with reference to the content of dapagliflozin, 5 mg. The following excipients from the groups of fillers (factor A) were used: a₁ – microcrystalline cellulose (MCC) of grade 200, a₂ – lactose monohydrate of grade 80, a₃ – a mixture of MCC of grade 102 with anhydrous lactose of grade 22 AN in the ratio of 3:1; disintegrants (factor B): b₁ – crospovidone XL-10, b2 – sodium croscarmellose, b₃ – sodium starch glycolate, glidants (factor C): c₁ – colloidal anhydrous silicon dioxide (aerosil 200), c₂ – talc, c₃ – polyethylene glycol (PEG) 8000, as well as magnesium stearate as a lubricant. The experimental data were subjected to statistical processing by the method of variance analysis.

Results and discussion. The development and introduction of new pharmaceuticals, effective analogs and generics is an important task as it contributes to the improvement of the quality of drug supply, treatment and safe use for patients with diabetes mellitus. A model for managing technological parameters at the stage of the pharmaceutical development has been developed; the target quality profile of the antidiabetic drug and tablets with API of SGLT-2 class – a derivative of gliflozin has been substantiated, and critical quality indicators have been determined. According to the model proposed, the optimal composition and technology of antidiabetic tablets with API of SGLT-2 class – a derivative of gliflozin calculated with reference to dapagliflozin, 5 mg, have been developed using an experiment planning matrix based on a 3*3 hyper-Greek-Latin square of the second order; the excipients have been selected; the effect of qualitative and quantitative factors and technological parameters on the pharmaco-technological properties of the tablet masses studied and tablet quality indicators, as well as critical indicators of the quality of the pharmaceutical product have been determined. Experimental studies and risk assessment have been carried out; based on the results, the optimal parameters of the technological process for the production of the antidiabetic drug in tablets with API of SGLT-2 class – a derivative of gliflozin – dapagliflozin have been substantiated.

Conclusions. Based on the results of the system analysis of the application of mathematical models in the production of pharmaceutical forms, it has been determined that mathematical modeling is a key stage for ensuring the quality of the technological process at the stage of the pharmaceutical development of an antidiabetic drug in tablets with API of SGLT-2 class – a derivative of gliflozin. The use of mathematical modeling in the course of the pharmaceutical development allows optimization at the stage of the experimental research of API, its polymorphic form, physico-chemical properties and pharmaco-technological indicators. A model for managing technological parameters at the stage of the pharmaceutical development has been proposed; the target quality profile of the antidiabetic drug and tablets with API of SGLT-2 class – a derivative of gliflozin has been substantiated; the optimal composition and technology of this pharmaceutical product has been developed.