Formulation and investigation of Self-Emulsifying Drug Delivery System (SEDDS) containing natural herb extract or different antitumor agents
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Approximately 70-75% of medications marketed worldwide are administrated per os and are proven to be less effective than desired. The majority of newly developed drugs represent poor aqueous solubility and stability. Drug instability results in lack of dose appropriateness after oral administration. Many different methods have been found to enhance drug dissolution rate and improve the physicochemical stability of drugs by applying surface-active agents, Cyclodextrins, nanoparticles or liposomes. Lipid-based drug delivery systems represent one of the most popular technologies for improving oral bioavailability and solubility. Micro- and nanoemulsions are lipid-based formulations that have a significant potential for drug delivery applications and self-micro/nanoemulsifying drug delivery systems (SM/NEDDS) considered as the best of these systems. Many studies suggested that SM/NEDDS are suitable carrier systems drugs which are very sensitive to hydrolysis. SM/NEDDS are characterized as isotropic mixtures of synthetic or natural oil and solid or liquid surface active agents or, alternatively, a single or several hydrophilic solvents and co-solvents and a drug which spontaneously forms oil-in-water (o/w) nanoemulsion/microemulsion droplets with water following a gentle stirring. In gastrointestinal fluid, this system spreads readily in the GI lumen and the agitation necessary for self-emulsification is provided by the gastric and intestinal digestive motility. After dilution with aqueous media, the oil droplets keep the drug inside of them or they form a micellar solution due to the very high surface-active agent concentration of such formulations. The drug will be delivered to the GI mucosa in dissolved state by these fine droplets; therefore, it will be readily available for absorption and its efficacy and bioavailability will also be increased. Micro/nanoemulsions improve oral bioavailability, protect drugs from enymatic hydrolysis and have high drug solubilization capacity and outstanding thermodynamic stability. The phenomenon of self-emulsification occurs only when specific combinations of pharmaceutical excipients are present. Several chemotherapeutic agents are used in the treatment of cervical cancer. Cisplatin is considered to be among the most effective drugs that treat advanced uterine and cervical cancer. Bleomycin sulfate is a mixture of glycopeptide antitumor antibiotics that has a unique mechanism of antitumor activity in cervical cancer. Ifosfamide is an anti-cancer drug and is widely used in the treatment of cervical, ovarian and testicular malignancies. In recent chemotherapy, cisplatin, bleomycin and ifosfamide (BIP) in combination has also been applied against inoperable cervical cancer. To decrease the serious side effects resulted from use of cytostatic medications it is necessary to formulate modern drug delivery systems which can reduce toxicity by decreasing the dose of potent therapeutic agent. SMEDDS are frequently used to increase the bioavailability of poorly soluble drugs by presenting and maintaining API in a dissolved state, in small droplets of oil with a ability to penetrate through various biological barriers. Plantago lanceolata has been widely used for medical purposes, such as the treatment of bleeding and tissue damage, antioxidant, anti-inflammatory, antibacterial antiviral and hepatoprotective. Some prominent pharmacological studies are outlined in the following section. Iridoid glucoside aucubin and its derivatives have been identified as important biologically active compounds in plantain by several studies. The main bioactive component of Plantago lanceolata is verbascoside (acteoside), which is a phenylpropanoid glycoside. However the high capability of its bioactive components for hydrolysis resulted in poor stability of this natural extract. SNEDDS is frequently used for the stabilization of natural products and these carrier systems may also increase the bioavailability of natural bioactive materials.