Inhibition of solution crystal growth of ritonavir by cellulose polymers – factors influencing polymer effectiveness

Ilevbare, Grace A.; Liu, Haoyu; Edgar, Kevin J.; Taylor, Lynne S.

doi:10.1039/c2ce25515d

Cited by 90 publications

(97 citation statements)

References 58 publications

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“…The hydrophobic polymer, P2VP, shows the opposite pattern of behavior where its presence in the water‐rich supernatant cannot be detected, with the vast majority of the polymer coprecipitating with felodipine. These observations are in agreement with previous studies of nucleation and growth where only moderately hydrophobic polymers were found to be effective inhibitors . Of course, polymer hydrophobicity is only one important polymer property, and additional structural features are likely to be important to achieve crystallization inhibition, and specific drug–polymer interactions such as hydrogen bonding may also play a role.…”

Section: Discussionsupporting

confidence: 92%

Trends in the Precipitation and Crystallization Behavior of Supersaturated Aqueous Solutions of Poorly Water-Soluble Drugs Assessed Using Synchrotron Radiation

Raina

Eerdenbrugh

Alonzo

et al. 2015

Journal of Pharmaceutical Sciences

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Section: Discussionsupporting

confidence: 92%

Trends in the Precipitation and Crystallization Behavior of Supersaturated Aqueous Solutions of Poorly Water-Soluble Drugs Assessed Using Synchrotron Radiation

Raina

Eerdenbrugh

Alonzo

et al. 2015

Journal of Pharmaceutical Sciences

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“…6a shows SEM micrograph of pure RIT crystals which displayed a similar morphology to that previously reported in the literature (35). Such crystalline structure was also observed in the case of the solid mixture formed by RIT and powdered SM (RIT-SM mixture) (Fig.…”

Section: Resultssupporting

confidence: 69%

Effect of Ultra-High Pressure Homogenization on the Interaction Between Bovine Casein Micelles and Ritonavir

et al. 2014

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Purpose The aim of this work was to develop a milk-based powder formulation appropriate for pediatric delivery of ritonavir (RIT). Methods Ultra-high pressure homogenization (UHPH) at 0.1, 300 and 500 MPa was used to process a dispersion of pasteurized skim milk (SM) and ritonavir. Loading efficiency was determined by RP-HPLC-UV; characterization of RIT:SM systems was carried out by apparent average hydrodynamic diameter and rheological measurements as well as different analytical techniques including Trp fluorescence, UV spectroscopy, DSC, FTIR and SEM; and delivery capacity of casein micelles was determined by in vitro experiments promoting ritonavir release. Results Ritonavir interacted efficiently with milk proteins, especially, casein micelles, regardless of the processing pressure; however, results suggest that, at 0.1 MPa, ritonavir interacts with caseins at the micellar surface, whilst, at 300 and 500 MPa, ritonavir is integrated to the protein matrix during UHPH treatment. Likewise, in vitro experiments showed that ritonavir release from micellar casein systems is pH dependent; with a high retention of ritonavir during simulated gastric digestion and a rapid delivery under conditions simulating the small intestine environment. Conclusions Skim milk powder, especially, casein micelles are potentially suitable and efficient carrier systems to develop novel milk-based and low-ethanol powder formulations of ritonavir appropriate for pediatric applications.

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“…Additives such as polymers at low solution concentrations do not generally enhance equilibrium crystalline solubility of small molecules (28). Rather, they inhibit nucleation (5,(29)(30)(31)(32), and/or crystal growth (33)(34)(35)(36) and thereby stabilize supersaturated solutions (29). In contrast, the other additives such as surfactants or complexing agents typically increase equilibrium solubility.…”

Section: Introductionmentioning

confidence: 99%

Impact of Solubilizing Additives on Supersaturation and Membrane Transport of Drugs

et al. 2015

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These findings clearly point out the flaws in using solute concentration in estimating solute activity or supersaturation, and reaffirm the use of flux measurements to understand supersaturated systems. Clear differentiation between solubilization and supersaturation, as well as thorough understanding of their respective impacts on membrane transport kinetics is important for the rational design of enabling formulations for poorly soluble compounds.

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Inhibition of solution crystal growth of ritonavir by cellulose polymers – factors influencing polymer effectiveness

Cited by 90 publications

References 58 publications

Trends in the Precipitation and Crystallization Behavior of Supersaturated Aqueous Solutions of Poorly Water-Soluble Drugs Assessed Using Synchrotron Radiation

Trends in the Precipitation and Crystallization Behavior of Supersaturated Aqueous Solutions of Poorly Water-Soluble Drugs Assessed Using Synchrotron Radiation

Effect of Ultra-High Pressure Homogenization on the Interaction Between Bovine Casein Micelles and Ritonavir

Impact of Solubilizing Additives on Supersaturation and Membrane Transport of Drugs

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