Development of the Composition and Technology for Obtaining Mini-Tablets of Propranolol Hydrochloride Using the Quality by Design Approach

Infantile hemangioma (IH) is a benign vascular neoplasm, occurring in 4–10 % of newborns and requiring timely therapy in cases of complicated progression. Currently, propranolol is recognized as the "gold standard" for IH treatment due to its proven efficacy and safety. However, in the Russian Federation, there are no readily available dosage forms (DFs) of propranolol for children, which creates a significant problem for pediatric practice. In this regard, the development of a PF that ensures accurate dosing and ease of use in children is relevant.

The aim. To develop the composition and technology for obtaining orodispersible mini-tablets (OMT) of propranolol hydrochloride for children using the Quality by Design (QbD) approach.

Materials and methods. The active pharmaceutical substance of propranolol hydrochloride and excipients were used: mannitol, microcrystalline cellulose 102 (MCC 102), crospovidone (CPV), sodium saccharin dihydrate, sodium stearyl fumarate (SSF), and colloidal silicon dioxide. The composition development was carried out using the QbD methodology, with experimental design planned using the Mixture Design (MD) method. The independent variables were the content of MCC 102, CPV, and SSF. OMT with a diameter of 3 mm were obtained by direct compression. The tablet blend and OMT were tested according to the methods presented in the State Pharmacopoeia of the Russian Federation, XV edition: flowability, bulk density and tapped density, crushing strength, friability, disintegration, and mass uniformity. The dose uniformity of the optimized composition was determined by HPLC.

Results. During the first stage, the target quality profile of the OMT was determined. In accordance with this, critical quality attributes (CQAs) were established: for the powder blend  – flowability, bulk density, tapped density; for the OMT – crushing strength, disintegration, friability, and dose uniformity. A composition was developed and optimized, which allowed the required values for all CQAs to be achieved. Statistical analysis revealed significant inter-component interactions affecting the crushing strength and disintegration of the OMT.

Conclusion. The composition and technology for obtaining orodispersible mini-tablets of propranolol hydrochloride have been developed.

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