Buoyant in situ Gels of Meloxicam-b-Cyclodextrin-Triethanolamine Ternary Complex for Oral Delivery; From a Box-Behnken Experimental Design to in vivo Activity Detail

Abstract

Meloxicam, a quite new cyclo-oxygenase inhibitor, belongs to the enolic acids class of NSAIDs. It is approved by FDA for the long-term treatment of osteoarthritis, rheumatoid arthritis, ankyloising spondolytis and so forth. It has a poor aqueous solubility [1] and therefore, on oral administration, it remains as unionized lipophilic form in the highly acidic stomach region. These conditions support the migration into the surface epithelial cells where it is dissociated into an ionized form that traps hydrogen ions, consequently producing highly critical local concentration, which lead to irritation in the stomach wall, stomach pain, rupture of gastric mucosa, gastric bleeding and ulceration [2,3], this risk may become much higher for people who are older in age [4], have poor health, or consume a large quantity of alcohol [5]. Moreover, the poor solubility and slow dissolution rate of the lipophilic drugs in the gastrointestinal fluid, besides posing difficulties in the manufacture of pharmaceutical preparations such as liquid orals, may also give rise to fluctuating oral bioavailability and poor therapeutic response of the drug [6].

Test

“…In Franz diffusion cell used to be stuffed with 10 mL fresh simulated tear luid in receptor compartment [9]. The receptor luid used to be kept at 37 ± 0.5 • C as well as constant moving employing Te lon coated magnetic stir.…”

Preparation and In Vitro and In Vivo Evaluation of Rectal In Situ Gel of Meloxicam Hydroxypropyl-β-cyclodextrin Inclusion Complex

“…Jafar et al improved the aqueous solubility and dissolution rate of meloxicam by preparing its ternary complex with β-cyclodextrin and triethanolamine. The solubility, stability and anti-inflammatory activity of meloxicam were successfully increased [ 13 ]. Ainurofiq et al investigated the inclusion complexes of MLX/β-CD incorporated into orally disintegrating tablets with excellent drug release and solubility enhancements [ 14 ].…”

Gastric floating in-situ gel as a strategy for improving anti-inflammatory activity of meloxicam

“…Over the years, substantial work mainly related to the meloxicam-cyclodextrin and/or hydrophilic excipient complex/ dispersion incorporated formulations such as tablets (Samprasit et al, 2015), suspension (Awasthi et al, 2011), suppositories (Gowthamarajan et al, 2002, and buccal patches (Jafar and Ali, 2011) has been reported in the literature. However, except our past work (Jafar et al, 2017), there is a lack of major evidences in the literature about the meloxicam ternary complex (prepared using cyclodextrins and alkali substance combination) incorporated gastric floating in-situ gels, even though this has been considered to be very beneficial from the therapeutic point of view.…”