In vitro profiling of fenofibrate solid dispersion mediated tablet formulation to treat high blood cholesterol

Objective:
Fenofibrate (FNF), an anti-hyperlipidemic agent, suffers from poor water solubility (0.000707 mg/ml) and belongs to class II drug as per BCS, shows a slow dissolution rate. The current investigation aimed to fabricate a fast-dissolving tablet of FNF (not available in the commercial market) using solid dispersion technique employing Vitamin E-D-α-Tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) as molecular biomaterial to enhance dissolution rate and reduce the time required to reach the systemic circulation.

Highlights

• Fenofibrate (FNF), an anti-hyperlipidemic agent, suffers from poor water solubility.
• Vitamin E TPGS shown efficacy as molecular biomaterial to enhance bioavailability.
• Fast dissolving tablets of FNF were prepared using Vit E TGPS mediated solid dispersion approach.
• The dissolution rate of FNF from fast dissolving tablets developed by Vitamin E TPGS mediated solid dispersion was further tested.
• The obtained data were kept into different in vitro kinetic models, including zero and first order, Higuchi and Hixon-Crowell model.
• The investigation present an industrially applicable solution to develop novel fast dissolving tablets.

Materials and methods:
Firstly, carrier material was selected based on the release study via preparing solid dispersion using the melting method, and prepared solid dispersion was characterized. Secondly, fast-dissolving tablets from solid dispersion were fabricated using the direct compression tool and characterized for X-ray diffraction (XRD) pattern, friability, hardness, content uniformity, weight variation and in vitro disintegration test.

Results:
The X-ray diffraction study confirmed the successful formation of solid dispersion using vitamin E TPGS by analyzing the change in physical state. The fabricated solid dispersion exhibited higher drug content than a physical mixture of FNF. An excipient interference study was also performed in methanol and 0.75% w/v sodium lauryl sulphate. It revealed no significant alterations in the absorption peak of FNF as analyzed using UV spectroscopy at 287 nm. In addition, water absorption ratio phase solubility and wetting time were also assessed. In -vitro release of FNF from developed tablets was found significantly higher (93.23%±3.11; p<0.001) as compared to prepared compressed tablet of pure FNF (12.21±2.34 %). The dissolution rate was also determined, and data were then kept to various kinetic models such as zero-order chemical kinetic, first-order chemical kinetic, Hixon-Crowell and Higuchi chemical kinetic.

Conclusion:
A complete and sequential in vitro and physicochemical characterization of developed formulation was carried out to set-up improved and effective treatment for high blood cholesterol.

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Umesh Atneriya, Devesh Kapoor, Jitendra Sainy, Rahul Maheshwari, In vitro profiling of fenofibrate solid dispersion mediated tablet formulation to treat high blood cholesterol, Annales Pharmaceutiques Françaises, 2022, ISSN 0003-4509,
https://doi.org/10.1016/j.pharma.2022.08.009.