The Significance of Utilizing In Vitro Transfer Model and Media Selection to Study the Dissolution Performance of Weak Ionizable Bases: Investigation Using Saquinavir as a Model Drug

Chegireddy, Mohith; Hanegave, Geeta K.; Lakshman, Dani; Urazov, Aman; Sree, K. Navya; Lewis, Shaila; Dengale, Swapnil J.

doi:10.1208/s12249-019-1563-0

Cited by 10 publications

(6 citation statements)

References 38 publications

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“…From the kinetic perspective, the polymer should be able to inhibit the precipitation of drugs in gastro-intestinal (GI) milieu into their respective crystalline form. Particularly, weakly basic drugs are amenable for precipitation in the intestine due to the predominance of unionized form therein ( 53 , 54 ). Further, if the polymer possesses surfactant properties, then partitioning of the drug in the micelles may help in improving the solubility.…”

Section: Selection Criteria For Polymeric Carriersmentioning

confidence: 99%

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

et al. 2020

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Solid dispersion is the preferred technology to prepare efficacious forms of BCS class-II/IV APIs. To prepare solid dispersions, there exist a wide variety of polymeric carriers with interesting physicochemical and thermochemical characteristics available at the disposal of a formulation scientist. Since the advent of the solid dispersion technology in the early 1960s, there have been more than 5000 scientific papers published in the subject area. This review discusses the polymeric carrier properties of most extensively used polymers PVP, Copovidone, PEG, HPMC, HPMCAS, and Soluplus® in the solid dispersion technology. The literature trends about preparation techniques, dissolution, and stability improvement are analyzed from the Scopus® database to enable a formulator to make an informed choice of polymeric carrier. The stability and extent of dissolution improvement are largely dependent upon the type of polymeric carrier employed to formulate solid dispersions. With the increasing acceptance of transfer dissolution setup in the research community, it is required to evaluate the crystallization/precipitation inhibition potential of polymers under dynamic pH shift conditions. Further, there is a need to develop a regulatory framework which provides definition and complete classification along with necessarily recommended studies to characterize and evaluate solid dispersions.

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Section: Selection Criteria For Polymeric Carriersmentioning

confidence: 99%

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

et al. 2020

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“…To investigate polymer–curcumin (Cur) formulations in FeSSIF, first, solutions of as-received curcumin (composed of 81% curcumin, 17% demethoxycurcumin, and 4% bisdemethoxycurcumin) in FeSSIF were examined. FeSSIF, composed of taurocholic acid (TC) and lipidsincluding LCin a maleic acid buffer (exact composition Table S1), imitates the small intestinal fluid in the fed state and is commonly used for studying the dissolution behavior of drugs and drug formulations. − FeSSIF-V2 was chosen as the latest commercially available FeSSIF version, ensuring straightforward reproducibility as well as comparison with previous work on efavirenz . Concentrations of up to 2 mM Cur could be fully dissolved in FeSSIF, significantly increasing the aqueous solubility from about 1.6 μM (0.6 μg/mL) .…”

Section: Resultsmentioning

confidence: 99%

“…Intestinal drug absorption is a key factor for oral bioavailability and is strongly impacted by the amount of the surfactant in the intestinal fluid. − Detailed compositional and morphological studies of human intestinal fluids (HIFs) showed different concentrations of bile salts, cholesterol, and (phospho)lipids and varying colloidal structures in fasted- and fed-state conditions . Simplified versions of HIF in the fed (FeSSIF) and fasted states (FaSSIF) were developed for simulating in vivo behavior. − A recent morphological analysis of bile colloids in the presence of the drugs imatinib and perphenazine showed that their size and structure depend strongly on the drug concentration. , Similarly, concentration-dependent aggregation was observed for mixtures of bile with polymeric excipients such as Pluronics, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and Triton X-100 but also in simulated intestinal fluids for the excipients Eudragit E and Soluplus . Vinarov et al showed that drug surfactant formulations exhibit concentration- as well as surfactant-dependent behavior in a bile salt-containing medium, resulting in various types of mixed colloids and decreased drug solubility for ionic surfactants .…”

Section: Introductionmentioning

confidence: 99%

Structural Investigation on How Guest Loading of Poly(2-oxazoline)-Based Micelles Affects the Interaction with Simulated Intestinal Fluids

Endres,

Ehrmanntraut,

Endres

et al. 2023

ACS Biomater. Sci. Eng.

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Drug loading of polymer micelles can have a profound effect on their particle size and morphology as well as their physicochemical properties. In turn, this influences performance in biological environments. For oral delivery of drugs, the intestinal environment is key, and consequently, a thorough structural understanding of what happens at this material−biology interface is required to understand in vivo performance and tailor improved delivery vehicles. In this study, we address this interface in vitro through a detailed structural characterization of the colloidal assemblies of polymeric micelles based on poly(2oxazolines) with three different guest loadings with the natural product curcumin (17−52 wt %) in fed-state simulated intestinal fluids (FeSSIF). For this, we employ NMR spectroscopy, in particular, 1 H NMR, 1 H− 1 H-NOESY, and 1 H DOSY experiments complemented by quantum chemical calculations and cryo-TEM measurements. Through this mixture of methods, we identified curcumin−taurocholate interactions as central interaction patterns alongside interactions with the polymer and lipids. Furthermore, curcumin molecules can be exchanged between polymer micelles and bile colloids, an important prerequisite for their uptake. Finally, increased loading of the polymer micelles with curcumin resulted in a larger number of vesicles as taurocholate�through coordination with Cur�is less available to form nanoparticles with the lipids. The loading-dependent behavior found in this study deviates from previous work on a different drug substance highlighting the need for further studies including different drug molecules and polymer types to improve the understanding of events on the molecular level.

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“…Hence, to specifically mimic the in vivo performance of a drug using a dissolution method, the dissolution medium must be able to simulate the GIT environment. The human GIT environment is complex, with pH variations as well as the presence of solubilizing bile salts and phospholipids along the GIT [ 51 , 52 ]. Second, DSSD was not completely converted to an amorphous form, as partial crystallinity was observed from XRPD.…”

Section: Resultsmentioning

confidence: 99%

Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir

Yarlagadda

Nayak

Brahmam

et al. 2023

Advances in Pharmacological and Pharmaceutical Sciences

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Amorphous salt solid dispersion (ASSD) of Dolutegravir amorphous salt (DSSD) was generated using quench cooling and compared to its Dolutegravir free acid solid dispersion (DFSD) to improve the solubility and bioavailability. Soluplus (SLP) was used as a polymeric carrier in both solid dispersions. The prepared DSSD and DFSD, physical mixtures, and individual compounds were characterized by employing DSC, XRPD, and FTIR to assess the formation of the single homogenous amorphous phase and the existence of intermolecular interactions. Partial crystallinity was observed for DSSD, unlike DFSD, which is completely amorphous. No intermolecular interactions were observed between the Dolutegravir sodium (DS)/Dolutegravir free acid (DF) and SLP from the FTIR spectra of DSSD and DFSD. Both DSSD and DFSD improved the solubility of Dolutegravir (DTG) to 5.7 and 4.54 folds compared to the pure forms. Similarly, drug release from DSSD and DFSD was 2 and 1.5 folds higher than that in the pure form, owing to the rapid dissolution of the drug from the formulations. The permeability of DSSD and DFSD was estimated using the dialysis membrane, which enhanced the DTG permeability. The improvement in in vitro studies was translated into in vivo pharmacokinetic profiles of DSSD and DFSD, where 4.0 and 5.6 folds, respectively, improved the Cmax of DTG.

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The Significance of Utilizing In Vitro Transfer Model and Media Selection to Study the Dissolution Performance of Weak Ionizable Bases: Investigation Using Saquinavir as a Model Drug

Cited by 10 publications

References 38 publications

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology

Structural Investigation on How Guest Loading of Poly(2-oxazoline)-Based Micelles Affects the Interaction with Simulated Intestinal Fluids

Exploring the Solubility and Bioavailability of Sodium Salt and Its Free Acid Solid Dispersions of Dolutegravir

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