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Aqueous and pH dependent coacervation method for taste masking of paracetamol via amorphous solid dispersion formation.

ABSTRACT: Taste masking of paracetamol was achieved by preparing amorphous solid dispersion (ASD) using modified coacervation method. The method is based on dissolving the drug and polymeric carrier in water adjusted to certain pH level. Then, precipitation of ASD granules is performed by gradually changing pH level. Therefore, the chosen drug and polymer should obtain appropriate acidic or basic groups to enable pH-dependent solvation. Moreover, using solubility enhancing additives such as sodium lauryl sulphate (SLS) and low viscosity polyethylene glycol (PEG 400) found to be essential in aiding drug/polymer aqueous solvation which enhanced amorphization, hence taste masking and drug loading. Solid dispersion between Paracetamol and Eudragit E was formed and that proved by FT-IR, DSC, PXRD and SEM. Also, Paracetamol was released after 2 min in 0.1 N hydrochloric acid medium and the taste of masking forms are accepted from all volunteers. Modified coacervation method does not involve organic solvents, high temperatures, or sophisticated instruments commonly used in taste masking methods. Using PEG 400 resulted in significantly higher drug loading and dissolution rate compared to SLS granules. Moreover, using previously reported scoring system for the evaluation of taste masking methods shows that pH dependent coacervation obtained high scoring over common methods and thus display a robust potential for industrial applications.

SUBMITTER: Al-Kasmi B

PROVIDER: S-EPMC8076289 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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Aqueous and pH dependent coacervation method for taste masking of paracetamol via amorphous solid dispersion formation.

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