Unveiling the Preparation and Characterization of Lercanidipine Hydrochloride in an Oral Solid Self-Nanoemulsion for Enhancing Oral Delivery

Chronic kidney disease (CKD) is becoming increasingly prevalent worldwide, particularly among the elderly, along with an increase in the incidence of hypertension and cardiovascular disorders. Developing lipid-based oral dosage forms with a higher expected bioavailability of antihypertensive drugs with nephroprotective effects poses a challenge. Lercanidipine hydrochloride (LRCH) is a newer type of third-generation dihydropyridine calcium channel blocker that functions as an antihypertensive and has significant nephroprotective effects. Due to its extensive first-pass metabolism, its bioavailability is about 10% and increases to 3-4 times when taken with a high-fat meal. Targeting this drug to the lymphatic system using the solid self-nano-emulsifying drug delivery system (SSNEDDS) is a promising approach for improving LRCH's bioavailability and dispersion rate. SSNEDDS combines the benefits of both liquid self-emulsifying and solid dosage forms, improving drug stability and extending storage time.

In this study, liquid SNEDDS composed of 10% peppermint oil, 67% Tween 20, and 22.5% propylene glycol was solidified using two adsorbent agent mixtures (SSNEDDS1: Avicel PH 101 and Aerosil 200) and (SSNEDDS2: Avicel PH 102 and Aerosil 200) separately. The prepared formulations were evaluated for powder flow, drug content, and an in-vitro dispersion test in comparison to the brand-marketed tablet as a standard or pure drug. DSC and X-ray diffraction analysis were also used.

The SSNEDDS2 shows excellent flowability, a higher drug content (99.761%), and a significantly higher and faster dispersion rate of 100% within 10 minutes compared to 92% of the marketed LRCH tablet and 18.1% of the pure drug for 60 minutes. The solid-state characterization of the formulation composed of SSNEDDS2 confirmed that the LRCH was in an amorphous form inside the solidified nano system without interacting with the excipient.

This study successfully prepared LRCH using the promising strategy of SSNEDDS as a hard gelatin capsule with a higher dispersion rate. It improved its stability and expected bioavailability compared to the brand-marketed tablet as the standard.