Optimization of the composition and technology of sitagliptin modified release floating capsules

Background. One way to improve existing oral medications whose active pharmaceutical ingredient (API) is primarily absorbed in the stomach or upper small intestine is to develop floating modified-release dosage forms (DFs). Sitagliptin, a hypoglycemic drug from the dipeptidylpetidase-4 inhibitor group used in the treatment of type 2 diabetes, possesses these properties. Therefore, the development of floating sitagliptin capsules is relevant.
Objective. Development and optimization of the composition and technology of sitagliptin floating capsules with a given release profile — release of more than 90 % of the API within 6 h, compliance with zero-order kinetics, as well as special properties — “total floating time” — 6 h and minimal “floating lag time”.
Materials and methods. The study examined floating capsules containing the sitagliptin API. The capsule mass was produced by wet granulation, and the dosing method mimicked the operation of machines that compacted the powder and then placed it into the capsule shell. The experimental design was based on the surface response method with a central composite design, regression and variance analysis, and optimization using generalized desirability. Release profiles were studied in a 0.1 M hydrochloric acid solution using a Dissolution Tester and UV spectrophotometry.
Results. As a result of optimization, the values of critical formulation attributes and process parameters for obtaining floating capsules of sitagliptin were established: the proportion of floating agent-matrix former in the total mass of matrix-forming polymers is 51.35 % (the proportion in the composition is 24.44 %) and the compaction force of the capsule mass — 1.90 kN, at which the DFs demonstrated a total release of 99.22±0.44 %, compliance of the dissolution kinetics with the zero-order model (R2 = 0.9764), “floating lag time” — 15.79±2.53 s and “total floating time” — more than 6 h.
Conclusions. During the study, the composition and technology of sitagliptin floating capsules with controlled release of the API, corresponding to zero-order kinetics, and 6-hour flotation were developed, based on the concept of “air incorporation during pressing or compaction of the mixture” using wet granulation with dosing into the shell using the “Piston-Tamp” principle. The resulting DFs potentially increase the absorption of the API and reduce the spike in plasma concentrations.

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