Co-amorphous palbociclib–organic acid systems with increased dissolution rate, enhanced physical stability and equivalent biosafety

Abstract

The preparation of co-amorphous drug systems by adding a small molecular excipient is a promising formulation in the modern pharmaceutical industry to improve the solubility, dissolution rate, and bioavailability of poorly soluble drugs. In this study, palbociclib co-amorphous systems with organic acids (succinic, tartaric, citric, and malic acid) at molar ratios of 1 : 1 were prepared by co-milling and characterized by differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR) and solid-state nuclear magnetic resonance (SS-NMR). These solid-state investigations have confirmed the formation of co-amorphous salts between PAL and organic acids. The solubility, dissolution rate and stability of the four co-amorphous drug systems were significantly improved compared with these of crystalline and amorphous palbociclib. The biosafety of the coamorphous drug systems was the same as that of palbociclib without affecting the efficacy of the drug and eliciting toxic side effects. These comprehensive approaches for the palbociclib-acid co-amorphous drug systems provided a theoretical basis for its clinical applications.

Generation of High Dose Inhalable Effervescent Dispersions against Pseudomonas aeruginosa Biofilms

“…However, thermal analysis showed that the CFX/TA (1:1) dispersions had a glass transition temperature (T g ) of 153.5°C. This is significantly higher than published data for amorphous CFX (87°C) and tartaric acid (24°C) ( 22 , 23 ). Such high T g compared to pure components suggests that the formed dispersion is co-amorphous salt.…”

Tumor-Targeted Fluorescent Proteinoid Nanocapsules Encapsulating Synergistic Drugs for Personalized Cancer Therapy

“…Pal, Alp and the P(RGD) proteinoid NCs were characterized by FTIR ( Figure S2 ). The spectrum of Alp ( Figure S2A ) demonstrates typical peaks at 1400–1000 cm −1 corresponding to C–F vibration, 1317 cm −1 (C–S stretching band [ 53 ]), 1640 cm −1 (carbonyl stretching band), broad peaks at 2770–2870 cm −1 (C-H and CH 3 groups), and a peak at 3500 cm −1 corresponding to N–H stretching band [ 54 ]. The spectrum of Pal ( Figure S2B ) demonstrates typical peaks at 1900–1640 cm −1 corresponding to the carbonyl stretching band, 2780–2960 cm −1 (C–H and CH 3 stretching band [ 55 ]) and 3500 cm −1 (N–H stretching band [ 54 ]).…”

“…The spectrum of Alp (Figure S2A) demonstrates typical peaks at 1400-1000 cm −1 corresponding to C-F vibration, 1317 cm −1 (C-S stretching band [53]), 1640 cm −1 (carbonyl stretching band), broad peaks at 2770-2870 cm −1 (C-H and CH 3 groups), and a peak at 3500 cm −1 corresponding to N-H stretching band [54]. The spectrum of Pal (Figure S2B) demonstrates typical peaks at 1900-1640 cm −1 corresponding to the carbonyl stretching band, 2780-2960 cm −1 (C-H and CH 3 stretching band [55]) and 3500 cm −1 (N-H stretching band [54]). The spectrum of P(RGD) (Figure S2C) demonstrates typical peaks of proteinoids [21,50] at 660 and 770 cm −1 (amine N-H wagging [56]) belonging to the arginine side chain, which possesses three atoms of nitrogen.…”

Cyclodextrin and its derivatives as effective excipients for amorphous ulipristal acetate systems

“… 6 For example, the limited miscibility of the drug with the polymer sometimes requires the addition of a large amount of polymer, which is disadvantageous for the usability, manufacturing, and cost. 7 Besides, ASDs also have problems of poor long-term stability as well as difficulty in manufacturing and processing. 8 Co-amorphous systems have been extensively studied in the pharmaceutical industry because of their excellent properties, such as promoting drug solubilization, enhancing drug stability, and improving drug delivery and absorption.…”