Cohesiveness of Powdered Co-Amorphous Olanzapine and Impact on Tablet Production

Costa, Nuno F. da; Pinto, João F.; Fernandes, Ana I.

doi:10.3390/msf2021005002

Cited by 2 publications

(6 citation statements)

References 3 publications

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“…Inversely, the addition of SAC to OLZ-containing formulations resulted in a substantial enhancement of the crushing strength of pellets (p < 0.01, by comparison with pellets containing OLZ in the matrix) (Table 2). These results are in line with previous publications which reported that tablets containing CAMs presented higher crushing strength values, as compared to those prepared using the respective crystalline counterparts [27,28,50]. This may be explained by the higher cohesiveness of OLZ in the CAM form [27,28,50] which may have increased the number and/or intensity of bonds established in the matrix of pellets.…”

Section: Preparation Of Pellets Containing Olanzapine In the Matrixsupporting

confidence: 92%

“…These results are in line with previous publications which reported that tablets containing CAMs presented higher crushing strength values, as compared to those prepared using the respective crystalline counterparts [27,28,50]. This may be explained by the higher cohesiveness of OLZ in the CAM form [27,28,50] which may have increased the number and/or intensity of bonds established in the matrix of pellets.…”

Section: Preparation Of Pellets Containing Olanzapine In the Matrixsupporting

confidence: 92%

“…Amorphous or CAMs prepared using these techniques are often blended with pharmaceutical excipients to enhance processability during manufacture (e.g., glidants), drug release (e.g., disintegrants), acceptability/compliance (e.g., sweeteners, colorants) and handling (e.g., fillers) by the patient. Additional pharmaceutical unit operations, such as dry or wet granulation, and pelletization, are often considered to improve the flowability of materials, if required [26][27][28]. However, the stress conditions (e.g., pressure, temperature, or moisture sorption) imposed to the system during these operations may result in instability and recrystallization of the amorphous content, negatively impacting drugs' bioavailability [29][30][31][32] and introducing product variability.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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In situ amorphization is a promising approach, considered in the present work, to enhance the solubility and dissolution rate of olanzapine, while minimizing the exposure of the amorphous material to the stress conditions applied during conventional processing. The production of pellets by extrusion/spheronization and the coating of inert beads were investigated as novel methods to promote the co-amorphization of olanzapine, a poorly water-soluble drug, and saccharin. Samples were characterized using differential scanning calorimetry, X-ray powder diffraction, Fourier-transform infrared spectroscopy and scanning electron microscopy, and dissolution and stability testing. The co-amorphous produced were compared with crystalline olanzapine, or physical mixture of olanzapine and saccharin. Results suggested that the addition of water to mixtures containing olanzapine and saccharin during the production of pellets, and the coating of inert beads, induced the in situ co-amorphization of these substances. The coating of inert beads enhanced the solubility and dissolution rate of olanzapine, especially when compared to pellets coated with the crystalline drug, but also with pellets containing the co-amorphous entity in the matrix of beads. Nine months stability tests (23 °C/60% RH) confirmed the preservation of the solid-state properties of the co-amorphous form on/in pellets. Overall, results highlighted the feasibility and benefits of in situ co-amorphization, either when the drug was entrapped in the pellets matrix, or preferentially applied directly on the surface of pellets.

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Section: Preparation Of Pellets Containing Olanzapine In the Matrixsupporting

confidence: 92%

Section: Preparation Of Pellets Containing Olanzapine In the Matrixsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Unfortunately, the high cohesiveness of extrudates containing OLZ and SAC prevented the production of pellets. The cohesiveness of OLZ-CAM was described previously [ 36 , 37 ].…”

Section: Resultsmentioning

confidence: 99%

“…To increase the stability of amorphous OLZ, co-amorphization of the drug with saccharin (SAC) has been attempted [ 35 ]. Unfortunately, the co-amorphization of OLZ resulted in a cohesive and non-free-flowing powder, impairing its handling per se (tableting or capsule filling) into dosage forms [ 36 , 37 ] and requiring the use of further down-streaming processing to overcome these drawbacks.…”

Section: Introductionmentioning

confidence: 99%

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

Costa

Daniels

Fernandes

et al. 2022

IJMS

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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.

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Cohesiveness of Powdered Co-Amorphous Olanzapine and Impact on Tablet Production

Cited by 2 publications

References 3 publications

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

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

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

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