Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization

Abstract

Irbesartan (IR) is an angiotensin II receptor antagonist drug with antihypertensive activity. IR bioavailability is limited due to poor solubility and first-pass metabolism. The current investigation aimed to design, develop, and characterize the cyclodextrin(s) (CD) complexed IR (IR-CD) loaded solid lipid nanoparticles (IR-CD-SLNs) for enhanced solubility, sustained release behavior, and subsequently improved bioavailability through oral administration. Based on phase solubility studies, solid complexes were prepared by the coacervation followed by lyophilization method and characterized for drug content, inclusion efficiency, solubility, and in vitro dissolution. IR-CD inclusion complexes demonstrated enhancement of solubility and dissolution rate of IR. However, the dissolution efficiency was significantly increased with hydroxypropyl-βCD (HP-βCD) inclusion complex than beta-CD (βCD). SLNs were obtained by hot homogenization coupled with the ultrasonication method with IR/HP-βCD inclusion complex loaded into Dynasan 112 and glycerol monostearate (GMS). SLNs were evaluated for physicochemical characteristics, in vitro release, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and physical stability at room temperature for two months. The optimized SLNs formulation showed particle size, polydispersity index, zeta potential, assay, and entrapment efficiency of 257.6 ± 5.1 nm, 0.21 ± 0.03, −30.5 ± 4.1 mV, 99.8 ± 2.5, and 93.7 ± 2.5%, respectively. IR-CD-SLN and IR-SLN dispersions showed sustained release of IR compared to the IR-CD inclusion complexes. DSC results complimented PXRD results by the absence of IR endothermic peak. Optimized IR-CD complex, IR-SLN, and IR-CD-SLN formulations were stable for two months at room temperature. Thus, the current IR oral formulation may exhibit improved oral bioavailability and prolonged antihypertensive activity, which may improve therapeutic outcomes in the treatment of hypertension and heart failure.

Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability

“…However, the scanning electron micrograph of the physical mixture demonstrated that IR remained dispersed and physically adsorbed on the surface of HPβCD not shown), signifying no physical complexation. This could have contributed to the faster dissolution profiles, reported in our earlier investigation [18]. The results were consistent with earlier published scanning electron micrographs.…”

Development of α-Tocopherol Succinate-Based Nanostructured Lipid Carriers for Delivery of Paclitaxel

“…Meanwhile, the release of the drug can be termed as the first order when the rate of the release of the drug is a function of the remaining concentration of the drug [ 63 ]. The Higuchi model for the release kinetics states that the rate of the release of the drug is a function of the square root of the time [ 41 , 64 ]. Lastly, Korsmeyer–Peppas is a semi-empirical model that can usually be used to describe the mechanism of the drug release phenomenon consisting of diffusion or swelling [ 41 , 65 ].…”

Design of Topical Moxifloxacin Mucoadhesive Nanoemulsion for the Management of Ocular Bacterial Infections

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