Lercanidipine hydrochloride loaded self-nanoemulsifying: A novel approach drug delivery for hypertension treatment as single dose liquid oral ampoule

Abstract

Lercanidipine Hydrochloride (LRCH) is a third-generation dihydropyridine calcium channel blocker. It is a safe antihypertensive drug with a protective effect on the kidneys in hypertensive patients who have diabetes or chronic renal disease. It is practically insoluble in water and belongs to the Biopharmaceutical Classification System (BCS) Class II. It has a high lipophilic nature due to its Log P value of 6.42, distinguishing it from older dihydropyridines. Its oral bioavailability is only 10%, and erratic absorption is observed due to its extensive first-pass metabolism. However, when taken with food, especially high-fat foods, its bioavailability can increase (30-40%). In this study, based on the pharmacokinetic characteristics of LRCH, it is suggested that this drug is an excellent candidate for formulating a unique self-nano emulsifying drug delivery system (SNEDDS) oral dosage form to overcome the challenges associated with this drug using peppermint oil as an oil phase, Tween 20 as a surfactant, and propylene glycol as a co-surfactant. Pseudo-ternary phase diagrams generated by varying ratios of surfactant and co-surfactant 1:1, 2:1, 3:1, as well as 4:1. The results showed that we successfully loaded LRCH in SNEDDS liquid formulation with different Smix ratios in excellent properties, ranging from (9 - 24) seconds emulsification time, (9.415 - 32.14) nm droplet size, (0.11 - 0.699) PDI, (98.265 - 99.889) % drug content, and higher dispersion rate (over 97% during 60 min). The Fourier transform infrared spectroscopy (FTIR) data show that the excipients are compatible with the drug, and the globules are indeed nano-sized and spherical, as confirmed by atomic force microscopy (AFM).

Keywords

• Lercanidipine HCL
• self-nano emulsifying
• Tween20
• pseudo ternary phase diagram
• oral ampule

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