Dataset Information

Amorphous solid dispersion formation via solvent granulation - A case study with ritonavir and lopinavir.

ABSTRACT: Herein, we evaluate the potential of using a simple solvent granulation process to prepare a binary drug amorphous solid dispersion (ASD) containing two anti-HIV drugs, ritonavir and lopinavir. The drugs were granulated onto a mixture of lactose and microcrystalline cellulose, followed by drying to remove the solvent. The resultant granules were characterized and each drug was found to be X-ray amorphous. No crystallization was observed following storage for 1 month under accelerated stability conditions (40?°C and 75% relative humidity). The dissolution behavior of the compacted granules was compared with the marketed formulation. The dissolution rate of ritonavir was found to be significantly retarded relative to the commercial product when the two drugs were co-granulated. However, comparable release could be achieved when each drug was individually granulated, followed by combination and compaction. The solvent granulation approach may be a viable method to make ASDs of low dose drugs with low crystallization tendencies.

SUBMITTER: Trasi NS

PROVIDER: S-EPMC6880113 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Amorphous solid dispersion formation via solvent granulation - A case study with ritonavir and lopinavir.

Trasi Niraj S NS Bhujbal Sonal S Zhou Qi Tony QT Taylor Lynne S LS

International journal of pharmaceutics: X 20191112

Herein, we evaluate the potential of using a simple solvent granulation process to prepare a binary drug amorphous solid dispersion (ASD) containing two anti-HIV drugs, ritonavir and lopinavir. The drugs were granulated onto a mixture of lactose and microcrystalline cellulose, followed by drying to remove the solvent. The resultant granules were characterized and each drug was found to be X-ray amorphous. No crystallization was observed following storage for 1 month under accelerated stability c ...[more]

PMID: 31788669

Similar Datasets

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

Amorphous solid dispersion formation via solvent granulation - A case study with ritonavir and lopinavir.

Publications

Amorphous solid dispersion formation via solvent granulation - A case study with ritonavir and lopinavir.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets