Design of an effective formulation for the oral administration of the anti-cholesterol drug, fenofibrate


General Information

12MED2524

Design of an effective formulation for the oral administration of the anti-cholesterol drug, fenofibrate

Medical And Health

Non-Communicable Diseases

Hyperlipidemia is the major risk factor for atherosclerosis and cardiovascular disease, which are blamed for 24% of all deaths in the Kingdom of Saudi Arabia. Statistics shows by the World Health Organization (WHO) that Saudi population is more prone to face high cholesterol levels in their bloods. One of the most potent and popular drug to reduce the cholesterols and triglycerides in the body is fenofibrate, which exhibits poor water solubility and low absorption after oral administration that requires significant delivery improvement. The purpose of the current research work is to design an effective lipid-based nano formulation to deliver fenofibrate, in a successful oral dosage form by increasing solubility in the GI and consequently improve bioavailability and reduce the pill burden. The content of this report concentrates initially on the development of ultrafast UHPLC method to determine fenofibrate in vitro and its metabolite fenofibric acid during in vivo studies. A series of nano formulations were designed by the help of LFCS framework (Type III systems) and examined predominantly the drug concentration upon aqueous dispersion in the intestine. Finally, fenofibrate loaded suitable nano formulations were exposed to in vitro digestion (lipolysis under fed and fasted conditions) and the bioavailability was evaluated in the rat model in vivo. The results from the characterization and solubility studies showed that formulations containing mixed glycerides were highly efficient (Type III, self nanoemulsifying drug delivery systems, SNEDDS) as they had higher solubility of the drug and produced nano-sized droplets. The dispersion studies confirmed that SNEDDS (containing polar mixed glycerides) can retain more than 98% drug in solution for more than 24 hrs in aqueous media. The in vitro digestion of SNEDDS was faster and mixed glycerides are good solvents for fenofibrate as rapidly digested but to improve fenofibrate concentration in post digestion products. The In vivo pharmacokinetics parameters of SNEDDS formulation in comparison to plain drug showed significant increase in Cmax and AUC(0-t), about 78% and 66%, respectively. The oral bioavailability of fenofibrate from SNEDDS in rats was about 1.7-fold enhanced as compared with the bioavailability from plain drug. Fenofibrate-loaded LFCS Type III SNEDDS formulations could be a potential oral pharmaceutical product (unit dose) for administering the poorly water-soluble drug, fenofibrate with an enhanced oral bioavailability with lower dose frequency. Due to the safety and patient compliance of our current liquid fenofibrate dosage product, it can have high acceptance in the kingdom. It will have relatively low alcohol content and an elegant appearance over the available marketed product. In addition, as the product’s raw materials are commercially available, its production costs will be exceedingly low. Potentially, many pharmaceutical industries and research centres will be interested in this product because of large number cardiovascular patients.

1. Develop suitable fast-dissolving liquid lipid formulations – a suite of products - for today's most promising water-insoluble cholesterol-lowering drug, fenofibrate 2. Encapsulate the liquid formulation with the maximum effective drug loading to improve product efficiency 3. Avoid precipitation, which is common with the currently marketed fenofibrate, so that the drug stays in solution in the gut to increase bioavailability and treatment effectiveness 4. Enhance bioavailability and reduce dosing frequency

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