article · Pharmaceutics
Candesartan cilexetil is an oral drug used to treat hypertension and heart failure, but its clinical effectiveness is constrained by poor water solubility, p-glycoprotein efflux, and hepatic metabolism, leading to low oral bioavailability. To address these limitations, a nanostructured lipid carrier formulation was developed using glyceryl monostearate and Capryol 90 through a hot homogenisation and ultrasonication method. The resulting spherical nanoparticles measured approximately 121.6 nanometres and achieved an encapsulation efficiency of 96.23 percent. Gastrointestinal absorption assessments demonstrated that absorption in the stomach was only 15.26 percent of that observed in the intestine. Furthermore, cellular uptake studies showed that the carriers are internalised by enterocytes before transport into the systemic circulation. Pharmacokinetic evaluations in rats revealed that this lipid carrier encapsulation increased the oral bioavailability of candesartan cilexetil by more than two-fold.
Many vital medications for cardiovascular conditions are poorly absorbed by the digestive system, reducing their overall efficacy. By using nanoscale lipid carriers to encapsulate and transport the drug across the intestinal wall, this approach significantly enhances the amount of active medicine reaching the bloodstream. This strategy could help improve oral delivery and performance for a range of poorly soluble pharmaceutical compounds.
This formulation offers an oral delivery method relevant to pharmaceutical companies developing therapies for hypertension and heart failure. Demonstrated in cellular uptake assays and rat pharmacokinetic models, the formulation is at an applied, preclinical stage of research. Advancing it toward real-world commercial use would require formal scale-up of the manufacturing process followed by safety and efficacy trials in human subjects.
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Candesartan Cilexetil (CC) is a prodrug widely used in the treatment of hypertension and heart failure, but it has some limitations, such as very poor aqueous solubility, high affinity to P-glycoprotein efflux mechanism, and hepatic first-pass metabolism. Therefore, it has very low oral bioavailability. In this study, glyceryl monostearate (GMS) and Capryol™ 90 were selected as solid and liquid lipids, respectively, to develop CC-NLC (nanostructured lipid carrier). CC was successfully encapsulated into NLP (CC-NLC) to enhance its oral bioavailability. CC-NLC was formulated using a hot homogenization-ultrasonication technique, and the physicochemical properties were characterized. The developed CC-NLC formulation was showed in nanometric size (121.6 ± 6.2 nm) with high encapsulation efficiency (96.23 ± 3.14%). Furthermore, it appeared almost spherical in morphology under a transmission electron microscope. The surgical experiment of the designed CC-NLC for absorption from the gastrointestinal tract revealed that CC-NLC absorption in the stomach was only 15.26% of that in the intestine. Otherwise, cellular uptake study exhibit that CC-NLCs should be internalized through the enterocytes after that transported through the systemic circulation. The pharmacokinetic results indicated that the oral bioavailability of CC was remarkably improved above 2-fold after encapsulation into nanostructured lipid carriers. These results ensured that nanostructured lipid carriers have a highly beneficial effect on improving the oral bioavailability of poorly water-soluble drugs, such as CC.
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DOI: 10.3390/pharmaceutics12111047
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