Dataset Information

Physicochemical Properties of Poly-Vinyl Polymers and Their Influence on Ketoprofen Amorphous Solid Dispersion Performance: A Polymer Selection Case Study.

ABSTRACT: When developing an amorphous solid dispersion (ASD), a prudent choice of polymer is critical to several aspects of ASD performance including: processability, solid state stability and dissolution rate. However, there is little guidance available to formulators to aid judicious polymer selection and a "trial and error" approach is often taken. This study aims to facilitate rational polymer selection and formulation design by generating ASDs using a range of poly-vinyl polymers and ketoprofen as a model active pharmaceutical ingredient (API) and evaluating several aspects of their performance. The molecular weight of the polymer and the ratio of vinyl pyrrolidone to vinyl acetate in the polymer were found to influence the relative humidity at which the relative humidity induced glass transition occurred, as well as the extent of ketoprofen supersaturation achieved during dynamic solubility testing. Interestingly, ASD tablets containing polymers with the vinyl pyrrolidone functional group exhibited higher tensile strengths than those without. This points towards the binder functionality of vinyl pyrrolidone. In conclusion, the physicochemical properties of poly-vinyl polymers greatly influence ketoprofen ASD performance and due regard should be paid to these properties in order to develop an ASD with the desired attributes.

SUBMITTER: Browne E

PROVIDER: S-EPMC7284699 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Physicochemical Properties of Poly-Vinyl Polymers and Their Influence on Ketoprofen Amorphous Solid Dispersion Performance: A Polymer Selection Case Study.

Browne Emer E Worku Zelalem A ZA Healy Anne Marie AM

Pharmaceutics 20200508 5

When developing an amorphous solid dispersion (ASD), a prudent choice of polymer is critical to several aspects of ASD performance including: processability, solid state stability and dissolution rate. However, there is little guidance available to formulators to aid judicious polymer selection and a "trial and error" approach is often taken. This study aims to facilitate rational polymer selection and formulation design by generating ASDs using a range of poly-vinyl polymers and ketoprofen as a ...[more]

PMID: 32397201

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Project description:Niclosamide is an FDA-approved anthelmintic that is being studied in clinical trials as a chemotherapeutic and broad-spectrum antiviral. Additionally, several other applications are currently in the preclinical stage. Unfortunately, niclosamide is a poorly water soluble molecule, with reduced oral bioavailability, which hinders its use for new indications. Moreover, niclosamide is a poor glass former; in other words, the molecule has a high tendency to recrystallize, and it is virtually impossible to generate a stable amorphous solid employing the neat molecule. Previously, our group reported the development of an amorphous solid dispersion (ASD) of niclosamide (niclosamide ASD) that generates nanoparticles during its dissolution, not only increasing niclosamide's apparent solubility from 6.6 ± 0.4 to 481.7 ± 22.2 µg/mL in fasted state simulated intestinal fluid (FaSSIF) but also its oral bioavailability 2.6-fold in Sprague-Dawley rats after being administered as a suspension. Nevertheless, niclosamide ASD undergoes recrystallization in acidic media, and an enteric oral dosage form is needed for its translation into the clinic. In this work, we further characterized the nanoparticles that generated during the dissolution of the niclosamide ASD. Cryogenic transmission electron microscopy (Cryo-TEM) and wide-angle X-ray scattering (WAXS) revealed that the nanoparticles were amorphous and had a particle size of ~150 nm. The oral dosage forms of niclosamide ASD were formulated using commercial enteric capsules (Capsuline® and EudracapTM) and as enteric-coated tablets. The enteric dosage forms were tested using pH-shift dissolution and acid-uptake tests, using the USP type II dissolution apparatus and the disintegration apparatus, respectively. The capsules exhibited a higher percentage of weight gain, and visual rupture of the Capsuline capsules was observed. Eudracap capsules protected the formulation from the acidic media, but polymer gelling and the formation of a nondispersible plug were noted during dissolution testing. In contrast, enteric-coated tablets protected the formulation from acid ingress and maintained the performance of niclosamide ASD granules during dissolution in FaSSIF media. These enteric-coated tablets were administered to beagle dogs at a niclosamide dose of 75 mg/kg, resulting in plasma concentrations of niclosamide higher than those reported in the literature using solubilized niclosamide at a higher dose (i.e., 100 mg/kg). In summary, an enteric oral dosage form of niclosamide ASD was formulated without hindering the generation of nanoparticles while maintaining the increase in the niclosamide's apparent solubility. The enteric-coated tablets successfully increased the niclosamide plasma levels in dogs when compared to a niclosamide solution prepared using organic solvents.

Dataset Information

Physicochemical Properties of Poly-Vinyl Polymers and Their Influence on Ketoprofen Amorphous Solid Dispersion Performance: A Polymer Selection Case Study.

Publications

Physicochemical Properties of Poly-Vinyl Polymers and Their Influence on Ketoprofen Amorphous Solid Dispersion Performance: A Polymer Selection Case Study.

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