Does the trihydrate of atorvastatin calcium possess a melting point?

Tizaoui, Chaima; Galai, Haykel; Clevers, Simon; Couvrat, Nicolas; Dupray, Valérie; Coquerel, Gérard; Tamarit, J. Ll.; Rietveld, Ivo B.

doi:10.1016/j.ejps.2020.105334

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…ATV-RM PXRD ( Figure 3B) presented two different semi-crystalline halos with diffraction angles between 7 and 12 • , and 15 and 25 • 2θ, respectively, and were related to the atorvastatin amorphous form used in the development of new commercial formulations [26]. This amorphous form of atorvastatin derives from the morphology of ATV-RM observed in the SEM studies.…”

Section: Powder X-ray Diffraction (Pxrd): Structure and Crystal Size mentioning

confidence: 85%

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Multiparticulate Systems of Ezetimibe Micellar System and Atorvastatin Solid Dispersion Efficacy of Low-Dose Ezetimibe/Atorvastatin on High-Fat Diet-Induced Hyperlipidemia and Hepatic Steatosis in Diabetic Rats

et al. 2021

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The aim of this study was to develop multiparticulate systems with a combination of ezetimibe micellar systems and atorvastatin solid dispersions using croscarmellose as a hydrophilic vehicle and Kolliphor RH40 as a surfactant. The presence of a surfactant with low hydrophilic polymer ratios produces the rapid dissolution of ezetimibe through a drug–polymer interaction that reduces its crystallinity. The solid dispersion of atorvastatin with low proportions of croscarmellose showed drug–polymer interactions sufficient to produce the fast dissolution of atorvastatin. Efficacy studies were performed in diabetic Goto-Kakizaki rats with induced hyperlipidemia. The administration of multiparticulate systems of ezetimibe and atorvastatin at low (2 and 6.7 mg/kg) and high (3 and 10 mg/kg) doses showed similar improvements in levels of cholesterol, triglycerides, lipoproteins, alanine transaminase, and aspartate transaminase compared to the high-fat diet group. Multiparticulate systems at low doses (2 and 6.7 mg/kg of ezetimibe and atorvastatin) had a similar improvement in hepatic steatosis compared to the administration of ezetimibe and atorvastatin raw materials at high doses (3 and 10 mg/kg). These results confirm the effectiveness of solid dispersions with low doses of ezetimibe and atorvastatin to reduce high lipid levels and hepatic steatosis in diabetic rats fed a high-fat diet.

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Section: Powder X-ray Diffraction (Pxrd): Structure and Crystal Size mentioning

confidence: 85%

“…explained by the swelling and water uptake of the hydrophilic carrier [7,9]. These improvements of dissolution profile could by related to the wettability increment of the amorphous form of ATV used in the formulation of commercial tablets [26].…”

Section: Dissolution Test Under Sink Conditionsmentioning

confidence: 99%

Multiparticulate Systems of Ezetimibe Micellar System and Atorvastatin Solid Dispersion Efficacy of Low-Dose Ezetimibe/Atorvastatin on High-Fat Diet-Induced Hyperlipidemia and Hepatic Steatosis in Diabetic Rats

et al. 2021

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“…The peaks of dehydration of the first kind of hydrate water and melting were independent, while the peaks of dehydrating the second and third kinds of hydrate water only overlapped partly. 53 Consequently, the calculated peak area could be more accurate than that in the literature 54 due to the more independent melting peak, and the melting enthalpy is listed in Table S4. The T m was approximately 154.5 °C, the dehydration enthalpy of the first kind of hydrate water (ΔH 1 ) was about 20 J/g, the sum of ΔH 2 and ΔH 3 of dehydration enthalpy of the second and the third kinds of hydrate water was about 130 J/g, and the ΔH m was about 5.5 J/g.…”

Section: Slowing Down the Molecule Exchange Between Solvent And Antis...mentioning

confidence: 99%

Crystal Agglomeration and Microscopic Molecular Exchange Mechanism in Antisolvent Crystallization

Qin,

Yang

2024

Crystal Growth & Design

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Agglomeration is a significant challenge in antisolvent crystallization, especially when it comes to crystallizing insoluble drugs. This study aimed to address this issue by taking a unique, dynamic molecular perspective and proposing a solution based on microscopic molecular exchange. Atorvastatin calcium, a widely prescribed medication for lowering blood lipids, was used as a case for antisolvent crystallization, which is also prone to agglomeration. Kinetic experiments revealed the rapid exchange between solvent and antisolvent, leading to precipitation occurring within a mere 0.0333 s. Thermodynamic investigations further showed that each droplet had the potential to generate an astonishing equivalent nucleation rate of up to 5 billion nuclei per second. The rapid precipitation and small nucleation region, coupled with a large number of nuclei, worsened the crystal agglomeration problem. However, it was found that this molecular exchange process can be slowed by the solvent composition. Specifically, when the methanol mole fraction in the crystallization system reached approximately 50%, the equivalent nucleation rate decreased significantly to about 100 million per second. Armed with this crucial finding, a strategy was devised to overcome agglomeration by simultaneously adding the solution and antisolvent to maintain a lower exchange rate, which effectively avoided agglomeration and promoted the purification of atorvastatin calcium.

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“…The absolute bioavailability of ATO is reported to be approximately 12%. [33][34][35][36] There have been previous reports on treatments with a combination of PC and ATO. Guo et al reported that the combined use of PC and ATO is effective for the therapeutic treatment of atherosclerosis in acute coronary syndrome patients.…”

Section: Introductionmentioning

confidence: 99%

Improved Dissolution Properties of Co-amorphous Probucol with Atorvastatin Calcium Trihydrate Prepared by Spray-Drying

Oyama,

Ogawa,

Kawai

et al. 2024

CHEMICAL & PHARMACEUTICAL BULLETIN

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A co-amorphous model drug was prepared by the spray-drying (SD) of probucol (PC) and atorvastatin calcium trihydrate salt (ATO) as low water solubility and co-former components, respectively. The physicochemical properties of the prepared samples were characterized by powder X-ray diffraction (PXRD) analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and dissolution tests. Stability tests were also conducted under a stress environment of 40 °C and 75% relative humidity. The results of PXRD measurements and thermal analysis suggested that PC and ATO form a co-amorphous system by SD. Thermal analysis also indicated an endothermic peak that followed an exotherm in amorphous PC and a physical mixture (PM) of amorphous PC and ATO; however, no endothermic peak was detected in the co-amorphous system. The dissolution profiles for PC in the co-amorphous sample composed of PC and ATO were improved compared to those for raw PC crystals or the PM. Stability tests indicated that the co-amorphous material formed by PC and ATO can be stored for 35 d without crystallization, whereas amorphous PC became crystallized within a day. Therefore, co-amorphization of PC and ATO prepared by SD is considered to be a useful method to improve the solubility of PC in water.

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Does the trihydrate of atorvastatin calcium possess a melting point?

Cited by 8 publications

References 35 publications

Multiparticulate Systems of Ezetimibe Micellar System and Atorvastatin Solid Dispersion Efficacy of Low-Dose Ezetimibe/Atorvastatin on High-Fat Diet-Induced Hyperlipidemia and Hepatic Steatosis in Diabetic Rats

Multiparticulate Systems of Ezetimibe Micellar System and Atorvastatin Solid Dispersion Efficacy of Low-Dose Ezetimibe/Atorvastatin on High-Fat Diet-Induced Hyperlipidemia and Hepatic Steatosis in Diabetic Rats

Crystal Agglomeration and Microscopic Molecular Exchange Mechanism in Antisolvent Crystallization

Improved Dissolution Properties of Co-amorphous Probucol with Atorvastatin Calcium Trihydrate Prepared by Spray-Drying

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