Topical drug delivery is an advantageous methodology for the treatment of local and systemic diseases [1]. A variety of drugs has been used in topical preparations for effective delivery of drugs across skin membrane [2]. Topical drug delivery can offer several advantages over other dosage forms, because it minimizes systemic side effects, prevents first pass effect, avoids gastro intestinal disturbances caused by the oral route and discomfort of parenteral route [3].
CTZ is a second generation anti-histamine, belongs to the class of piperazines and is used for the treatment of allergic rhinitis, seasonal conjunctivitis, perennial allergic rhinitis, pruritus urticaria of allergic origin [4]. CTZ binds selectively to the peripheral H1 histamine receptors and prevents the release of histamine which causes allergy or allergic reactions [5]. CTZ reverses the effect of histamine, decreases vascular permeability, reduces the infiltration of (anti-inflammatory) cells in allergic rhinitis thus, exerts anti-inflammatory activity [6]. NIMS is an aromatic ether, derived from nitrobenzene and acts as COX-2 inhibiter, and is widely used used for the treatment of pain, dysmenorrhea and osteoarthritis [7]. NIMS selectively inhibits the cyclooxygenase-2 (which is a precursor of prostaglandin and converts arachidonic-acid to cyclic endoperoxides), thus, blocks the synthesis of prostaglandins. This blockage accounts for their anti-platelet, antipyretic and analgesic activity [8]. It targets a number of key mediators of inflammatory process such as proteolytic enzymes; COX 2 mediated prostaglandins, histamine and free radicals [9].
Emulgels are emulsions; either oil in water (o/w) or water in oil (w/o) type and usually gelled with the gelling agent [10, 11]. They are a suitable vehicle for the delivery of poorly water soluble or hydrophobic drugs. To overcome the limitations with the use of ointment, lotion and creams, a new approach based on the combination of gel and emulsion was emerged [12]. The first and foremost purpose of formulating emulgel is the targeted drug delivery with enhanced therapeutic efficacy and to lower the side effects associated with the systemic absorption of drugs [13]. Emulgel is considered as a stable formulation and an optimum medium for the delivery of hydrophobic drugs [14, 15]. Oil in water system is selected for the entrapment of lipophilic drugs and water in oil system for the encapsulation of hydrophilic drugs [16, 17]. Several studies were performed previously to investigate the use of emulgels as drug delivery system. In 2020, Chauhan et al. developed an emulgel containing green tea extract and avocado oil for the treatment of acne which was stable, effective and cosmetically acceptable [18]. In 2021, Constantino-González et al. prepared amikacin sulfate (loaded emulgel) by using Pluronic F-127 for the treatment of mycetoma [19].
NIMS is available in market as an oral dosage form but its oral use is associated with various side effects like nausea, heart burn, diarrhea, vomiting, epigastric pain and gastrointestinal disturbance and serious liver damage [20]. Similarly, CTZ HCl, belongs to class III (high solubility and low permeability) is an antihistamine (H1 receptor antagonist) used orally and no topical preparation is available in the market [21]. Therefore, the aim of this study was to prepare a topical semisolid emulgel of CTZ and NIMS for the treatment of dermatological allergic diseases and to get rid of side effects associated with the oral use of NIMS. The concentration of gelling agent (carbopol 940) was varied to investigate its effect on the rheology and drug release of highly soluble and very sparingly soluble drug. The in-vitro drug release was studied using Franz diffusion cell.