Cellulose derivatives as effective recrystallization inhibitor for ternary ritonavir solid dispersions: In vitro-in vivo evaluation

Guan, Qingran; Ma, Qisan; Zhao, Yanna; Jiang, Xinxin; Zhang, Huaizhen; Liu, Min; Wang, Zhengping; Han, Jun

doi:10.1016/j.carbpol.2021.118562

Cited by 20 publications

(7 citation statements)

References 47 publications

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“…DSC was utilized to elucidate the thermal transitions of crystalline ritonavir, physical mixtures, and formulations at the temperature range of 10–180 °C. As shown in Figure 2 A, the melting point and endothermic peak of crystalline ritonavir for Form II were approximately 123 °C and 127 °C, respectively, corresponding to values reported previously [ 40 ]. The endothermic peak of ritonavir could also be detected in the physical mixtures of ritonavir/PVPVA/Span 20.…”

Section: Resultssupporting

confidence: 83%

“…Since the heating and cooling ramps of cyclic DSC curves were applied under a dry nitrogen atmosphere, the effect of moisture content on T g was also excluded as much as possible. Because the solvent evaporation method allows the drug/polymer/surfactant to exist in the solution system in a dissolved state with a higher degree of mixing [ 52 ], the T g of drug/polymer/surfactant was measured using the previously described solvent evaporation method [ 40 ]. Figure S4 shows that the T g of ritonavir/PVPVA/Span 20 prepared by solvent evaporation was 69.99 °C.…”

Section: Resultsmentioning

confidence: 99%

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Effect of Span 20 Feeding Zone in the Twin Screw Extruder on the Properties of Amorphous Solid Dispersion of Ritonavir

Wang

Zhao

et al. 2023

Pharmaceutics

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A ternary amorphous solid dispersion (ASD) system consisting of drug/polymer/surfactant is receiving increased attention to improve the oral bioavailability of poorly water-soluble drugs. The effect of polymers has been extensively studied, while the impact of surfactants has not yet to be studied to the same extent. Challenging questions to be answered are whether the surfactants should be added with the drug or separately and the resulting differences between the two operating processes. By adjusting the liquid feeding zone for Span 20 in the hot-melt twin screw extruder equipment, we investigated the effect of Span 20 on the properties of the polyvinylpyrrolidone/vinyl acetate (PVPVA)-based ASD formulations of ritonavir. We found that with the delayed feeding positions of Span 20 in the twin screw extruder, the ability of the ternary ASDs to maintain the supersaturation of the milled extrudates was observed to be significantly enhanced. Furthermore, adding surfactant after a thorough mixing of polymer and drug could decrease the molecular mobility of ternary ASD formulations. In addition, the effects of Span 20 on the complex viscosity and structure of PVPVA were also investigated. The delayed addition of Span 20 could improve the complex viscosity of PVPVA, thus leading to the drug precipitation inhibition. In conclusion, the delayed addition of Span 20 in the twin screw extruder and prolonging the mixing time of the drug and polymer may be critical to the maintenance of supersaturation.

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Section: Resultssupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Effect of Span 20 Feeding Zone in the Twin Screw Extruder on the Properties of Amorphous Solid Dispersion of Ritonavir

Wang

Zhao

et al. 2023

Pharmaceutics

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“…To prevent this, recrystallization inhibitors can be used to maintain this state. As it is seen in the thermograms, SLS was found most effective recrystallization inhibitor compared to other surfactants [51].…”

Section: Dsc and Ftir Studiesmentioning

confidence: 69%

“…In the study, the solubility enhancement was obtained using Span 20, Tween 80 and SLS surfactants which are used as solubilizing and wetting agents. According to the results, SLS provided a very high solubility enhancement compared to other nonionic surfactants and had a very efficient role in the inhibition of recrystallizationcomparedtocellulosederivatives [51]. Inrecentstudies, SLS is generally used alongside a polymer.…”

Section: Preparation Of Solid Dispersionsmentioning

confidence: 99%

Solubilization Effect of Anionic, Cationic and Nonionic Surfactants on Coenzyme Q10 Solid Dispersion

ERGİN¹

2023

jrp

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Coenzyme Q10 ( CoQ10) is an oil-soluble vitamin-like benzoquinone compound. Coenzyme Q10 plays a role in providing membrane stability, energy conversion and ATP production. It is also one of the important antioxidants in the body. The bioavailability of coenzyme Q10 is very low due to its low solubility in water and its large molecular mass. Among the solubility enhancement approaches, solid dispersions (SDs) are one of the most promising strategies. The use of suitable carrier and methodology plays a significant role in the biological response. In terms of a carrier, solid dispersions are classified broadly the third group. Surfactant-based SDs are called third-generation solid dispersions. To evaluate the surfactant effect on solubilization of CoQ10, three different surfactants of varying ratios between 1:1, 1:3 and 1:5 (w/w) were used namely sodium dodecylsulfate (SDS) (anionic), cetyl trimethyl ammonium bromide (CTAB) (cationic) and Pluronic F127 (non-ionic). CoQ10 solid dispersions were characterized in terms of particle size, polydispersity index, zeta potential, FTIR spectroscopy, DSC analysis, saturation solubility and in vitro dissolution studies. To compare dissolution rate, area under the dissolution curve (AUC), Mean Dissolution Time (MDT), mean residence time of the drug substance molecules in the dosage form (MRT), and dissolutio nefficiency % (DE%) were calculated. All the formulations showed improvement in the aqueous solubility, while the dissolution rate was increased only by Pluronic F127 (p<0.05). Among the surfactants, Pluronic F127-based SDs were found superior to other surfactants. The results revealed that surfactant-based SDs offered great success in improving the therapeutic efficacy of CoQ10.

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“…Plasma samples were analyzed using LC-MS/MS (Waters TQ-S) with telmisartan as the internal standard (IS) [ 32 , 33 ]. Briefly, 400 μL of IS solution (0.25 µg/mL of IS acetonitrile solution) was added to thawed plasma samples at ambient temperature and mixed vigorously by vortexing.…”

Section: Methodsmentioning

confidence: 99%

The Development of an Oral Solution Containing Nirmatrelvir and Ritonavir and Assessment of Its Pharmacokinetics and Stability

Wang,

Ding,

Wang

et al. 2024

Pharmaceutics

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Paxlovid®, a co-packaged medication comprised of separate tablets containing two active ingredients, nirmatrelvir (NRV) and ritonavir (RTV), exhibits good effectiveness against coronavirus disease 2019 (COVID-19). However, the size of the NRV/RTV tablets makes them difficult for some patients to swallow, especially the elderly and those with dysphagia. Therefore, an oral liquid formulation that can overcome this shortcoming and improve patient compliance is required. In this study, we developed a liquid formulation containing NRV and RTV by adopting strategies that used co-solvents and surfactants to enhance the solubility and inhibit possible recrystallization. The in vitro release results showed that NRV and RTV could be maintained at high concentrations in solution for a certain period in the investigated media. In vivo studies in rats showed that the oral bioavailability of NRV/RTV solution was significantly enhanced. Compared to Paxlovid® tablets, the AUC(0–t) of NRV and RTV increased by 6.1 and 3.8 times, respectively, while the Cmax increased by 5.5 times for both. Furthermore, the promoting effect of the absorption of RTV on the bioavailability of NRV was confirmed. Experiments with a beagle showed a similar trend. Stability studies were also conducted at 4 °C, 25 °C, and 40 °C for 90 days, indicating that the oral liquid formulation was physically and chemically stable. This study can be used as a valuable resource for developing and applying oral liquid NRV/RTV formulations in a clinical context.

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Cellulose derivatives as effective recrystallization inhibitor for ternary ritonavir solid dispersions: In vitro-in vivo evaluation

Cited by 20 publications

References 47 publications

Effect of Span 20 Feeding Zone in the Twin Screw Extruder on the Properties of Amorphous Solid Dispersion of Ritonavir

Effect of Span 20 Feeding Zone in the Twin Screw Extruder on the Properties of Amorphous Solid Dispersion of Ritonavir

Solubilization Effect of Anionic, Cationic and Nonionic Surfactants on Coenzyme Q10 Solid Dispersion

The Development of an Oral Solution Containing Nirmatrelvir and Ritonavir and Assessment of Its Pharmacokinetics and Stability

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