Development and Evaluation of Orodispersible Tablets Containing Ketoprofen.

BACKGROUND: Orodispersible Tablets (ODTs) are an option to facilitate the intake of pharmaceutical solid dosage forms, which dissolve in the mouth within 30 seconds releasing the drug immediately with no need for water intake or chewing. OBJECTIVE: The main goal of our study is the technological development of lactose-free orodispersible tablets that contain ketoprofen. METHODS: We assessed different variables during the pharmaceutical development of ODTs: compression techniques conducted after a wet granulation process, aiming to optimize the flow properties of the formulation, and a suspension freeze-drying molded in blisters. We developed three formulations for each method, each containing one of the superdisintegrants: croscarmellose, crospovidone, or starch glycolate. RESULTS: During the production of ODTs, we performed quality control of the granulation process, since the production of pellets contributed to the enhancement of the disintegration time and content homogeneity. Quality control tests for ODTs produced by freeze-drying were also satisfactory, despite significant changes in the final physical aspect of these products when compared to that of ODTs produced by compression. In addition, the disintegration times of ODTs produced by freeze-drying were substantially higher. Furthermore, these tablets displayed greater friability and pose a challenge to the control of a standard individual weight. CONCLUSION: Among the superdisintegrants, croscarmellose contributed most significantly to reduce the disintegration time and to dissolve KTP effectively in 20 minutes.

Solid-State Characterization of Different Crystalline Forms of Sitagliptin.

Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-4, used for the treatment of type 2 diabetes mellitus. The crystal structure of active pharmaceutical solids determines their physical and chemical properties. The polymorphism, solvates and hydrates can influence the free energy, thermodynamic parameters, solubility, solid-state stability, processability and dissolution rate, besides directly affecting the bioavailability. Thus, the physicochemical characterization of an active pharmaceutical ingredient is required to guarantee the rational development of new dosage forms. In this context, we describe herein the solid-state characterization of three crystalline forms of sitagliptin: sitagliptin phosphate monohydrate, sitagliptin phosphate anhydrous and sitagliptin base form. The investigation was carried out using differential scanning calorimetry (DSC), thermogravimetry (TG)/derivative thermogravimetry (DTG), spectroscopic techniques, X-ray powder diffraction (XRPD) and morphological analysis by scanning electron microscopy. The thermal analysis revealed that during the dehydration of sitagliptin phosphate monohydrate (Tpeak = 134.43 °C, ΔH = -1.15 J g-1) there is a characteristic crystalline transition event, which alters the physicochemical parameters of the drug, such as the melting point and solubility. The crystalline behavior of sitagliptin base form differs from that of sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous, mainly with regard to the lower temperature of the fusion event. The melting point (Tpeak) values obtained were 120.29 °C for sitagliptin base form, 206.37 °C for sitagliptin phosphate monohydrate and 214.92 °C for sitagliptin phosphate anhydrous. In relation to the thermal stability, sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous showed a slight difference; however, both are more thermostable than the base molecule. Therefore, through this study it was possible to establish the most suitable crystalline form of sitagliptin for the development of a safe, effective and appropriate pharmaceutical dosage form.