Study of paracetamol-containing pastilles produced by melt technology

Abstract

The focus of this work was to apply melt technology for the formulation of a pastille containing paracetamol (PCT) in a solid dispersion with two sugar alcohols (xylitol and mannitol) and polyethylene glycol 6000 (PEG) as the carrier system components. Optimization of the pastillization was performed both statistically by using the Box-Behnken design and experimentally by determining the phase diagrams. For the latter and recrystallization of the components, differential scanning calorimetry detection was utilized. The developed pastilles consisted of a eutectic mixture of xylitol (61.25 %) and mannitol (15.31 %) with PEG (7.81 %) as carrier system together with PCT (15.63 %). The components of the pastilles underwent recrystallization at different rates for 5 days. Transmission Raman spectroscopy revealed the homogeneous distribution of the PCT in the pastille. X-ray powder diffractometry showed that the recrystallization of the PCT resulted in its monoclinic form I, while dispersive Raman spectroscopy detected both the monoclinic and orthorhombic forms. The drop-melted pastilles displayed relatively high hardness, and the PCT dissolved within 15 min. It is concluded that pastillization can be achieved through melt technology and the structure and the technological parameters of the pastille are suitable for the development of lozenges as a solid dosage form for children therapy.

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

“…The first scenario, where a drug is molecularly dispersed in the amorphous domains of PEG, wherein the recrystallization of a drug is usually observed after storing the dispersion at room temperature. The scenario is described for weak glasses like paracetamol (111), Telmisartan (112), and Celecoxib (113). The second scenario, where the polymer is in amorphous form, herein, it is established that PEG has the potential to vitrify after fusion and subsequent cooling.…”

Robustness testing of milling process, analyzing the particle size distribution and crystallinity of the milled samples

“…It should be noted that recently the characterization of the investigated materials (e.g., crystallinity) using DSC as a semiquantitative conventional method has become common in scientific research [7][8][9]. It provides a possibility to predict the crystallinity of the examined materials, but to verify the accuracy of thermoanalytical measurements, the X-ray powder diffraction test is required [10,11].…”

“…Due to the lack of crystalline structure and the crystal lattice breaking force, less energy is needed for solubilization. Nevertheless, additional stabilization is needed for the preservation of the amorphous form from recrystallization [5][6][7].…”

Formulation of microcomposites and pastilles using spray-drying and melt technology

“…xylitol and sorbitol, as these are very similar molecules. In addition, our former studies (Katona et al, 2016) on similar pastilles containing no sorbitol revealed no such anomaly in the residuals (see the insert in Fig. 7C).…”

“…In our previous studies we applied melt technology for the formulation of pastilles containing PCT (15.63%) as a model active agent, plus xylitol (61.25%), mannitol (15.31%) and polyethylene glycol 6000 (PEG 6000) (7.81%) as carriers (Katona et al, 2016). It was found that the components of the pastilles underwent recrystallization at different rates within the first 5 days after production, and phase separation, resulting in the appearance of a "shell" on the surface of the pastilles was detected.…”