Amorphous and Co-Amorphous Olanzapine Stability in Formulations Intended for Wet Granulation and Pelletization

Abstract

The preparation of amorphous and co-amorphous systems (CAMs) effectively addresses the solubility and bioavailability issues of poorly water-soluble chemical entities. However, stress conditions imposed during common pharmaceutical processing (e.g., tableting) may cause the recrystallization of the systems, warranting close stability monitoring throughout production. This work aimed at assessing the water and heat stability of amorphous olanzapine (OLZ) and OLZ-CAMs when subject to wet granulation and pelletization. Starting materials and products were characterized using calorimetry, diffractometry and spectroscopy, and their performance behavior was evaluated by dissolution testing. The results indicated that amorphous OLZ was reconverted back to a crystalline state after exposure to water and heat; conversely, OLZ-CAMs stabilized with saccharin (SAC), a sulfonic acid, did not show any significant loss of the amorphous content, confirming the higher stability of OLZ in the CAM. Besides resistance under the processing conditions of the dosage forms considered, OLZ-CAMs presented a higher solubility and dissolution rate than the respective crystalline counterpart. Furthermore, in situ co-amorphization of OLZ and SAC during granule production with high fractions of water unveils the possibility of reducing production steps and associated costs.

In Situ Co-Amorphization of Olanzapine in the Matrix and on the Coat of Pellets

“…These results suggest the co-amorphization of both compounds during processing (Figure 5). Water-induced co-amorphization of OLZ was previously reported by the authors [49].…”

Co-Dispersion Delivery Systems with Solubilizing Carriers Improving the Solubility and Permeability of Cannabinoids (Cannabidiol, Cannabidiolic Acid, and Cannabichromene) from Cannabis sativa (Henola Variety) Inflorescences

“…As model carriers, biopolymer Soluplus and Neusilin US2 were applied. The systems of cannabinoids with carriers ( Figure 2 ) were prepared using a solvent-evaporation method which enables the incorporation of a wide range of active ingredients into the resulting systems [ 74 , 75 ].…”

Terahertz Spectroscopy for Non-Destructive Solid-State Investigation of Norfloxacin in Paper Tablets after Wet Granulation

“…The industrial tablet manufacturing process requires an adequate flowability of the excipients [ 52 ]. To overcome the poor flowability of solids (e.g., smartFilm cutouts) their transfer into granules by wet granulation has been extensively studied [ 15 ]. However, during this process, the ingredients are exposed to the granulation liquid (i.e., water), which can lead to crystallization [ 18 , 19 ] and subsequently affect the solubility of an API and its bioavailability [ 7 ].…”

“…Norfloxacin-loaded smartFilms and smartFilm granules were produced as described previously [ 11 , 15 ] with minor modifications. First, paper sheets with a size of 5 × 5 cm 2 and an individual mass of approximately 200 mg were prepared.…”

“…To overcome this, i.e., to transform smartFilms into solids with appropriate flowability for high-speed tablet manufacturing, wet granulation has been recently used to produce granules from the paper pieces [ 12 , 13 , 14 ]. Moreover, the processing of granules produced by wet granulation was investigated in several studies, showing further advantages such as improved compressibility and uniform drug distribution [ 15 , 16 , 17 ]. The manufacture of granules involves, first, the addition of a granulation liquid (i.e., water) to a blend of paper (i.e., smartFilms) and sucrose powder to promote agglomeration into granules.…”