Sulfonic Acid Derivatives in the Production of Stable Co-Amorphous Systems for Solubility Enhancement

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

doi:10.1016/j.xphs.2022.08.023

Cited by 5 publications

(9 citation statements)

References 65 publications

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“…As shown previously [15], OLZ benefits from co-amorphization with saccharin (SAC, pK a = 1.6 [16], Figure 1B), both in terms of solubility (5896 vs. 41 mg/L for OLZ-CAM and pure crystalline OLZ, respectively) and dissolution rate of the drug (88.7 vs. 25.2% of drug release for OLZ-CAM and pure crystalline OLZ, respectively). Both olanzapine [17] and saccharine [18] are reportedly stable under the conditions used for co-amorphization [15]. The formation of a stable CAM between OLZ and SAC was explained by salification, rather than hydrogen or π-π bonds, which was supported by the huge difference between the pK a of OLZ and SAC (∆pK a = 6.06) [15].…”

Section: Introductionsupporting

confidence: 74%

“…The positive impact of the establishment of intermolecular interactions, particularly salt formation, on the physical stability of CAMs is well described in the literature [10,[19][20][21][22]. Accordingly, the higher solubility and dissolution rate of OLZ in the CAM may foresee an improved bioavailability of the drug in the amorphous form, as compared to its crystalline counterpart [15].…”

Section: Introductionmentioning

confidence: 92%

“…Both olanzapine [17] and saccharine [18] are reportedly stable under the conditions used for co-amorphization [15]. The formation of a stable CAM between OLZ and SAC was explained by salification, rather than hydrogen or π-π bonds, which was supported by the huge difference between the pK a of OLZ and SAC (∆pK a = 6.06) [15]. The positive impact of the establishment of intermolecular interactions, particularly salt formation, on the physical stability of CAMs is well described in the literature [10,[19][20][21][22].…”

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: Introductionsupporting

confidence: 74%

Section: Introductionmentioning

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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“…Co-amorphization of OLZ, using SAC as co-former, has been previously reported to enhance the solubility (approximately 145 and 40-fold increase, respectively, as compared to the solubility of crystalline and amorphous OLZ) and stability of the drug (OLZ-CAM > 24 weeks vs. amorphous OLZ < 1 week at 75% RH/25 °C) [ 34 , 44 ]. In the present work, amorphization of the pure drug by quench cooling or co-amorphization with a co-former (SAC) by solvent evaporation was confirmed using X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) characterization methods.…”

Section: Resultsmentioning

confidence: 99%

“…In fact, as a drug belonging to class II of the biopharmaceutical classification system (BCS) with many transient polymorphs (e.g., the most stable form I polymorph was considered in this study, as a control), it benefits from a transformation at the molecular level to overcome such limitations. Previous studies have shown that the preparation of amorphous OLZ by quench cooling could be used to enhance the solubility of the drug (3.5-fold enhancement compared to crystalline OLZ, 141.4 ± 1.5 vs. 40.6 ± 1.4 mg/L, in phosphate buffer pH 8.0) [ 34 ]. However, the low stability of the system resulted in the rapid recrystallization of the amorphous drug back to its crystalline counterpart.…”

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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Tranilast-matrine co-amorphous system: Strong intermolecular interactions, improved solubility, and physiochemical stability

Chen

et al. 2023

International Journal of Pharmaceutics

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Sulfonic Acid Derivatives in the Production of Stable Co-Amorphous Systems for Solubility Enhancement

Cited by 5 publications

References 65 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

Tranilast-matrine co-amorphous system: Strong intermolecular interactions, improved solubility, and physiochemical stability

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