Cocrystallization and amorphization induced by drug–excipient interaction improves the physical properties of acyclovir

Masuda, Takaaki; Yoshihashi, Yasuo; Yonemochi, Etsuo; Fujii, Kotaro; Uekusa, Hidehiro; Terada, Katsuhide

doi:10.1016/j.ijpharm.2011.10.046

Cited by 114 publications

(74 citation statements)

References 36 publications

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“…These melting point is different with constituent materials ACV and NCT. Hence, this is indicate that ACV-NCT cocrystal with ethanol and glacial acetic acid was successfully formed [17]. Whereas, no peaks were found for HCl 0.1 N.…”

Section: Characterization Studymentioning

confidence: 64%

Preparation of Acyclovir-Nicotinamide Cocrystal by Solvent Evaporation Technique With Variation of Solvent

Nawatila

W²,

Siswodihardjo³

et al. 2017

Asian J Pharm Clin Res

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Objective: This research aims to prepare cocrystal of acyclovir (ACV)-nicotinamide (NCT) by solvent evaporation with a variation of solvent (ethanol, glacial acetic acid, and HCl 0.1 N) to improve the bioavailability of ACV as an antiviral drug. Methods:Cocrystal were developed by solvent evaporation with 1:1 molar fraction, using variation of solvent such as ethanol, glacial acetic acid, and HCl 0.1 N. Further, the prepared ACV-NCT cocrystal were characterized for differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), and in vitro dissolution.Results: DSC thermogram showed that ACV-NCT cocrystal in ethanol and glacial acetic acid exhibited new endothermic peak at 221.16°C and 216.40°C, whereas no peaks were found for HCl 0.1 N. PXRD diffractogram showed that ACV-NCT cocrystal in ethanol exhibited new diffraction peaks at 2θ 5.9°; 9.2°; dan 13.3°, whereas no peaks were found for glacial acetic acid and HCl 0.1 N. FT-IR characterization of ACV-NCT cocrystal in ethanol showed disappearance of transmission peaks at 3373/cm indicating the loss of NH bands of NCT. Furthermore, C=O of ACV and NCT were observed at 1693/cm, and 1666/cm indicated a formation of hydrogen bonding between ACV and NCT. SEM micrographs showed that cocrystals have a different shape compared to ACV and NCT. DE 15 showed that there was a significant increase of ACV-NCT cocrystal dissolution rate in ethanol compared to the physical mixture and ACV. Conclusion:The study concludes that ACV-NCT cocrystal in ethanol were successfully formed and the dissolution rate of ACV can increase significantly (α=0.05).

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Section: Characterization Studymentioning

confidence: 64%

Preparation of Acyclovir-Nicotinamide Cocrystal by Solvent Evaporation Technique With Variation of Solvent

Nawatila

W²,

Siswodihardjo³

et al. 2017

Asian J Pharm Clin Res

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“…3 showed new endothermic peak appears at 176.23°C (ΔH=1.07 Jg ) for AS cocrystal (glacial acetic acid). The thermal behavior of the cocrystals was distinct with a different melting transition from that seen with either of the individual components; this suggests the formation of a new phase [11]. The changes in peak position may be attributed to change in powder geometry of samples during preparation [20].…”

Section: Resultsmentioning

confidence: 90%

“…Due to its poor solubility and permeability, the bioavailability of acyclovir attains just 15-30% [11][12][13][14]. Carboxylic acids are considered as coformers to form cocrystals with acyclovir.…”

Section: Introductionmentioning

confidence: 99%

Cocrystallization Acyclovir-Succinic Acid Using Solvent Evaporation Methods

Winantari

Setyawan

Siswodihardjo

et al. 2017

Asian J Pharm Clin Res

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Objective: The aim of this research is to prepare and characterize cocrystals of acyclovir through cocrystallization of acyclovir-succinic acid (AS) to improve the physical properties of the drug.Methods: AS cocrystals were prepared using solvent evaporation method. The cocrystals were characterized by polarization microscope, scanning electron microscopy (SEM), differential scanning calorimetry, powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy.Results: Physical characterization using polarization microscope and SEM showed the AS cocrystals have unique crystal habit and morphology. Phase diagram at a molar ratio of 50:50% (acyclovir:succinic acid) showed a decrease in the melting temperature, i.e., 176.23°C in comparison with the melting point of the constituent materials (acyclovir 253.53°C and succinic acid 187.29°C). The PXRD pattern of AS cocrystals (ethanol) exhibited new diffraction peaks at 2θ=5.91°; 9.16°; and 13.40°. Besides, cocrystals of AS (glacial acetic acid) indicated new peaks at 2θ=5.98°; 9.19°; and 13.43°. Furthermore, there was a shift in the N-H, O-H, and C=O. Conclusion:Cocrystallization of AS acid in ethanol and glacial acetic acid were successfully formed using solvent evaporation methods.

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“…However, the hydrated and anhydrous forms have poor bioavailability [4] because ACV is a class IV drug according to biopharmaceutical system or BCS. Furthermore, hydrated and anhydrous forms of ACV are not stable at all relative humidity conditions [5][6][7]. It would be desirable to have a solid form of ACV with improved solubility and stability.…”

Section: Introductionmentioning

confidence: 99%

Co-Amorphization of Acyclovir with Oxalic Acid as an Excipient

Rohani¹,

Sarkar²

2017

J Appl Pharm

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The present article provides a novel technique for the co-amorphous formation of acyclovir and oxalic acid as an excipient. Designated as ACV-oxalic acid, methods for the preparation thereof and its use in pharmaceutical applications are described. The co-amorphous ACV-oxalic acid was characterized by powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. Stability with respect to relative humidity (RH) for the co-amorphous ACV-oxalic acid was evaluated and compared with the parent ACV. The aqueous solubility of the co-amorphous ACV-oxalic acid was significantly improved (about 8 times more soluble) at 35°C compared to that of the parent Acyclovir base.

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Cocrystallization and amorphization induced by drug–excipient interaction improves the physical properties of acyclovir

Cited by 114 publications

References 36 publications

Preparation of Acyclovir-Nicotinamide Cocrystal by Solvent Evaporation Technique With Variation of Solvent

Preparation of Acyclovir-Nicotinamide Cocrystal by Solvent Evaporation Technique With Variation of Solvent

Cocrystallization Acyclovir-Succinic Acid Using Solvent Evaporation Methods

Co-Amorphization of Acyclovir with Oxalic Acid as an Excipient

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