# Immobilization of Levocyetririzine on Mesoporous Silica for Antiallergenic Gel Formulation
## 1 Introduction  
A significant proportion of the population today is affected by allergic diseases, with allergic rhinitis impacting 25-35% of people, and its prevalence continues to rise. The most common symptoms include immediate allergic or anaphylactic reactions, which are caused by the immune response triggered by the IgE-type antibody. When these antibodies bind to surface receptors of various immune cells, they prompt them to release histamine and leukotrienes, which cause vasodilation, edema, and itching. The symptoms significantly worsen the patient's quality of life, affecting their cognitive and emotional functioning [1]. Another inflammatory skin disease is atopic dermatitis (AD), with a prevalence of 15-30%. Two types of this chronic and pruritic skin syndrome are known, called intrinsic AD and extrinsic AD. Extrinsic AD affects about 80% of patients and is marked by IgE-mediated sensitization, leading to elevated serum IgE levels [2]. Oral H1-antihistamines, such as leukotriene antagonists, and corticosteroids, are usually used in their therapies [3, 4]. Levocyetrizine (Levo) is a second-generation histamine H1-receptor antagonist, which effectively reduces allergic symptoms, such as runny nose, sneezing, watery eyes, orreactions to insect bites and rashes. It does not prevent the release of histamine from mast cells but inhibits its binding to receptors [5]. Levocetririize is chemically a piperazine derivative (Figure 1A), as the hydrochloric acid salt of the R(levo)-enantiomer of cetriize named officially as levocetriize dihydrochloride (LevdC, C\({}_{21}\)H\({}_{25}\)CN\({}_{2}\)O\({}_{3}\)*2 HCl; 2-[4-[(R)-(4-chlorophenylenyl)-phenyl-methyl]piperazine-1-yl]ethoxy]acetic acid dihydrochloride, and is commercially available. The other cetriize stereoisomer, the S(dextro)-enantiomer (Figure 1B), differs significantly from the R-enantiomer in its pharmacokinetic and pharmacodynamic effects. It is 30 times less effective than the R-enantiomer. Cetriize dihydrochloride, on the other hand, is also available on the market as a racemic mixture in a less effective form for financial reasons [6]. Levo is barely metabolized in the human body and is mostly excreted unchanged [7]. Levo belongs to the new types of antihistamines and as such has few known side effects (iterdness, drowsiness, sinus pain, ear infection, cough, fever, nose bleeding, vomiting, diarrhea, constipation, weight gain, or dry mouth) [8], and it hardly enters the central nervous system, like the first-generation antihistamine preparations. However, achieving a greater effect and reducing the dose is an important aspect in the development of Levo-containing preparations. They are usually used orally in the form of tablets, capsules, syrups, drops, and oral liquids [9]. The systemically effective product is, therefore, of limited use. In contrast, locally applied Levo would provide targeted therapy and reduce systemic side effects (drowsiness, fever, cough); however, a topical preparation is available on the market only for a racemic mixture drug. A topical formulation of cetriize has also been investigated in various dosage forms [10; 11]. There was a need for the development of a topical gel preparation for the symptomatic treatment of urtic on the skin that can have a more prolonged effect with fewer side effects, alleviating itching, and effectively reducing skin edema. One approach for enhancing efficacy while minimizing side effects is to reduce the particle size of the active ingredient [12; 13]. Various traditional (e.g., melt quenching, hot melt extrusion) and new methods (supercritical fluid technique, freeze-drying, spray-drying, and spray freeze-drying) [14; 15; 16] are available for this purpose.