Influence of preparation methods on physicochemical and pharmacokinetic properties of co-amorphous formulations: the case of co-amorphous atorvastatin: naringin

Nair, Athira and Varma, Raghava K and Gourishetti, Karthik and Bhat, Krishnamurthy and Dengale, Swapnil J (2020) Influence of preparation methods on physicochemical and pharmacokinetic properties of co-amorphous formulations: the case of co-amorphous atorvastatin: naringin. Journal of Pharmaceutical Innovation, 15 (3). pp. 365-379. ISSN 1872-5120

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Abstract

Purpose The goal of the study was to investigate the influence of processing methods on the physicochemical and pharmaco�kinetic properties of co-amorphous materials. Methods Co-amorphous formulations of atorvastatin (ATV) and naringin (NRG) in the molar ratio 1:1 were prepared by quench cooling (ANQC), solvent evaporation (ANSE), and ball milling (ANBM) and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (XRPD), and Fourier transform infrared spectroscopy (FTIR). Further, the performance of prepared co-amorphous formulations was evaluated in vitro and in vivo. Results All processing methods yielded homogeneous co-amorphous formulation, which was confirmed by single glass transi�tion (Tg) event and diffuse halo in DSC and XRPD, respectively. Irrespective of processing method employed, all co-amorphous formulations were found stable at 30 °C for 90 days in dry conditions (under vacuum). Significant improvement in the solubility of ATV was observed in ANQC and ANSE co-amorphous formulations, highest being 56-fold for the later. ATV from ANSE formulation showed highest drug release (97%), while surprisingly ANQC showed significantly lower ATV release as compared to the physical mixture. Amongst three preparation methods, solubility advantage of ANSE could translate into efficacious pharmacokinetic parameters, where the improvement in ATV exposure (AUC 0-t) and plasma concentration (Cmax) were found 4.5-fold and 7-fold, respectively, as compared to the physical mixture. Conclusion It was concluded that the preparation methods of co-amorphous formulations have a profound effect on physical properties like stability, physicochemical properties like solubility, dissolution rate, and pharmacokinetic properties like AUC and Cmax.

Item Type: Article
Uncontrolled Keywords: Co-amorphous ; Atorvastatin ; Naringin ; Ball milling ; Solvent evaporation ; Quench cooling.
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Quality Assurance
Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 15 Oct 2020 04:03
Last Modified: 15 Oct 2020 04:03
URI: http://eprints.manipal.edu/id/eprint/155834

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