Co-amorphous simvastatin and glipizide combinations show improved physical stability without evidence of intermolecular interactions

Löbmann, Korbinian; Strachan, Clare J.; Grohganz, Holger; Korhonen, Ossi; Laitinen, Riikka

doi:10.1016/j.ejpb.2012.02.004

Cited by 204 publications

(152 citation statements)

References 34 publications

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“…These systems show molecular interaction between two components (17) or without evidence of intermolecular interactions (13). In this investigation, ATC in the presence of NIC was completely converted to the coamorphous form, as it is evident from disappearance of typical pattern of ATC in PXRD and melting endotherm in DSC thermogram (32)(33).…”

Section: Disscussionmentioning

confidence: 80%

Coamorphous Atorvastatin Calcium to Improve its Physicochemical and Pharmacokinetic Properties

et al. 2013

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-Purpose: Atorvastatin calcium (ATC) is classified as class II (low solubility and high permeability) compound according to the biopharmaceutical classification system. The amorphous form of ATC possesses higher solubility, dissolution rate, and bioavailability than its crystalline form. Coamorphous drug system is a new and emerging method to prepare stable amorphous forms, in this case leading to the improved stability of ATC in dissolution medium. Methods: In this study, coamorphous form of ATC and nicotinamide (ATC-NIC) was prepared from solvent evaporation method and characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD). The intrinsic dissolution rate and solubility of ATC-NIC were determined along with plasma concentrations of ATC using HPLC after oral dosing in rats. Results: The crystalline ATC was converted to coamorphous form revealing a molecular interaction between ATC and NIC. The intrinsic dissolution rate, solubility and plasma concentration of coamorphous ATC-NIC are higher than those of crystalline ATC. ATC-NIC coamorphous system showed greater solution stability than those reported in the literature for amorphous ATC. Conclusions: Coamorphous ATC-NIC has improved physicochemical and pharmacokinetic properties as compared to ATC.

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Section: Disscussionmentioning

confidence: 80%

Coamorphous Atorvastatin Calcium to Improve its Physicochemical and Pharmacokinetic Properties

et al. 2013

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“…Recently, Rade et al have developed co-amorphous binary mixtures of various drugs viz indomethacin-ranitidine hydrochloride (18), in which it has been concluded that both indomethacin and ranitidine hydrochloride were fully converted into the amorphous state through molecular interaction after comilling in contrast to the partially crystalline form of individually milled drugs. In contrast, the simvastatin-glipizide co-amorphous mixture showed improved physical stability without evidence of intermolecular interactions as studied by Lobmann et al (19). Alleso et al have illustrated the stabilization of the naproxen-cimetidine amorphous mixtures dictated by molecular-level interactions rather than bulk-level phenomena (20).…”

Section: Introductionmentioning

confidence: 92%

Co-Amorphous Combination of Nateglinide-Metformin Hydrochloride for Dissolution Enhancement

Wairkar

Gaud

2015

AAPS PharmSciTech

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Abstract. The aim of the present work was to prepare a co-amorphous mixture (COAM) of Nateglinide and Metformin hydrochloride to enhance the dissolution rate of poorly soluble Nateglinide. Nateglinide (120 mg) and Metformin hydrochloride (500 mg) COAM, as a dose ratio, were prepared by ball-milling technique. COAMs were characterized for saturation solubility, amorphism and physicochemical interactions (X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR)), SEM, in vitro dissolution, and stability studies. Solubility studies revealed a sevenfold rise in solubility of Nateglinide from 0.061 to 0.423 mg/ml in dose ratio of COAM. Solid-state characterization of COAM suggested amorphization of Nateglinide after 6 h of ball milling. XRPD and DSC studies confirmed amorphism in Nateglinide, whereas FTIR elucidated hydrogen interactions (proton exchange between Nateglinide and Metformin hydrochloride). Interestingly, due to low energy of fusion, Nateglinide was completely amorphized and stabilized by Metformin hydrochloride. Consequently, in vitro drug release showed significant increase in dissolution of Nateglinide in COAM, irrespective of dissolution medium. However, little change was observed in the solubility and dissolution profile of Metformin hydrochloride, revealing small change in its crystallinity. Stability data indicated no traces of devitrification in XRPD of stability sample of COAM, and % drug release remained unaffected at accelerated storage conditions. Amorphism of Nateglinide, proton exchange with Metformin hydrochloride, and stabilization of its amorphous form have been noted in ball-milled COAM of NateglinideMetformin hydrochloride, revealing enhanced dissolution of Nateglinide. Thus, COAM of NateglinideMetformin hydrochloride system is a promising approach for combination therapy in diabetic patients.

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“…These systems have been found to provide high stability and enhanced dissolution rates for the drugs. There are several publications in the area of amorphous binary systems like ritonavir with indomethacin, naproxen with cimetidine, simvastatin with glipizide, and atorvastatin with nicotinamide [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Formulation and Evaluation of Tablet Prepared by Coamorphous System Containing Anti-Hypertensive and Anti-Hyperlipidemic Drug

Adahalli

Talluri

2016

Int J Pharm Pharm Sci

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Objective: Amlodipine besylate (AML) and Atorvastatin calcium (ATR) belong to biopharmaceutical classification system (BCS) class II (i.e. low solubility and high permeability) which leads to variable bioavailability. Hence, the aim of this study was to enhance the solubility of both drugs by utilizing the co-amorphous technique. This converted form and physical mixture of both drugs were utilized in the formulation of tablets. Methods:The co-amorphous system was prepared by using rotary flash evaporator. Solubility study was carried out to investigate the dissolution advantage of prepared co-amorphous form. Total twelve formulations were formulated by keeping constant drugs concentrations utilizing direct compression technique among which F1 to F6 contains co-amorphous AML-ATR (Co-A AML-ATR) and F7 to F12 contains a physical mixture of AML and ATR as active pharmaceutical ingredient (APIs). Pre-compression and post-compression studies were carried out to all twelve formulations. Stability study was performed to the optimized formulations as per ICH guidelines.Results: Mixture obtained after evaporation was found to become amorphous. FTIR study shows no evidence of intermolecular interactions between AML and ATR. The solubility of both AML and ATR were increased in almost one fold as compared to their respective crystalline counterparts. Pre-compression parameters of all twelve formulations blend fall under excellent to fair to flow properties. Post-compression parameters of all twelve formulations were within the specifications. But in vitro drug release of formulations F5, F6, F11, and F12 showed % drug release as per IP. Stability study of optimized formulations was observed with, no significant difference in % drug release. Conclusion:The co-amorphous system can be prepared by utilizing rotary flash evaporator and the same was confirmed by XRPD and FTIR studies. The dissolution rate of the co-amorphous system was greater than that of the crystalline counterpart. Based on the results; F5 and F6 are considered as optimized formulations. Optimized formulations were stable during the stability study.

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Co-amorphous simvastatin and glipizide combinations show improved physical stability without evidence of intermolecular interactions

Cited by 204 publications

References 34 publications

Coamorphous Atorvastatin Calcium to Improve its Physicochemical and Pharmacokinetic Properties

Coamorphous Atorvastatin Calcium to Improve its Physicochemical and Pharmacokinetic Properties

Co-Amorphous Combination of Nateglinide-Metformin Hydrochloride for Dissolution Enhancement

Formulation and Evaluation of Tablet Prepared by Coamorphous System Containing Anti-Hypertensive and Anti-Hyperlipidemic Drug

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