Strategic Formulation of Losartan Potassium Nano-invasome Gel: A Comprehensive Multiscale Pharmacokinetic Study

Angiotensin II receptor antagonist losartan potassium (LP) is a medication that can be consumed orally and is used to treat hypertension. LP has a short biological half-life of 1.5–2.5 h and a broad first-pass metabolism in the liver (67%). LP dose can therefore be greatly reduced in transdermal formulation because it avoids the hepatic elimination. The current study set out to create an LP nano-invasome (NI) gel to increase the drug’s absorption and decrease its elimination. NI were formulated by the thin-film hydration technique, and to optimize it, the Box-Behnken design was employed. The losartan potassium–optimized nano-invasome (LPNIopt) has a vesicle size of 190 ± 1.5 nm, an entrapment efficiency of 92.2 ± 0.01%, a PDI of 0.363 ± 0.02, and a zeta potential of − 23.4 ± 0.32 mV. According to transmission electron microscopy, the vesicles had a spherical shape and 147 nm in size. The ATR-FTIR study reveals that the drug and lipid do not interact with each other. DSC thermogram demonstrated that the LP is included within the LPNI matrix. The ideal viscosity of LPNIopt gel was 11426 ± 2.51 cps, and its notable spreadability was 7.9 ± 0.01 g·cm/s. When comparing the permeability of LPNIopt gel to pure medication, it was higher. The absence of oedema or swelling in the skin observed with LPNIopt gel indicates that the developed formulation is non-irritating. In vivo study refers to the increased half-life of drug with respect to pure drug. The results showed that invasomal gel is a viable carrier and an appealing strategy for improved LP topical administration to treat hypertension.