With the advent of therapeutics, oral delivery is the most widely used and the most convenient route of drug delivery. Despite of phenomenal advances in other dosage routes viz. injectable, inhalable, transdermal, nasal, oral delivery still remain well ahead of the pack as the preferred delivery route. Higher concentration is focused in making the oral formulations viable if it is not immediately viable, than in plumping for an alternative delivery method. The top 50 drugs selling in the world have 84% oral delivery. Variety of approaches have been tried to enhance the oral bioavailability of poorly soluble drugs using the excipients with approved or GRAS (generally regarded as safe) status. Micronization by spray-drying, freeze-drying, crystallization and milling; nanosizing into nanoparticles by various techniques with high-pressure homogenization being one of most efficient; crystal engineering of polymorphs, hydrates, solvates, co-crystals, supercritical fluid and sonocrystallization; solid dispersions developed by melt-mixing, solvent evaporation, supercritical fluid and melt extrusion; solubilizing ability of cyclodextrins; solid lipid nanoparticles prepared by high-pressure homogenization and microemulsion technology and other colloidal drug delivery systems including emulsions, microemulsions, self-emulsified and self-microemulsified drug delivery systems, liposomes etc. have been widely researched for enhancement of oral bioavailability. Other attempts of enhancing oral bioavailability include Solid lipid nanoparticles, mucoadhesive delivery system, lipid digestion models, Supersaturatable Formulations, nanoemulsion, nanocapsules, fast-dispersing dosage forms and pH-sensitive supramolecular assemblies[3–10].
Diabetes is a group of chronic carbohydrate metabolism disorders resulting from diminished or absent action of insulin by altered secretion, decreased insulin efficacy or combination of both the factors leading to hyperglycemia. Type II diabetes is the most common type counting about 90-95% of the diagnosed cases, characterized with normal or even excess of insulin levels with insulin resistance being the major cause of increased glucose levels. Metformin a biguanide enhances insulin sensitivity, found to be effective in impaired glucose tolerance, obese patients and patients with cardiovascular diseases and is used as first line of drug in treatment of Type II diabetes.
The oral bioavailability of Metformin is 50-60% as it is BCS (Biopharmaceutical Classification System) class III drug and has site-specific absorption in the GI tract. The drug has negligible plasma protein binding, relatively short half life of 1.5-4.5 hours and requires administration of 500 mg dose two or three times a day. Moreover the drug suffers from serious but rare side effects of lactic acidosis with 50% mortality, chest pain, allergic reactions accompanied by high incidences of concomitant gastrointestinal symptoms such as diarrhea, abdominal discomfort, vomiting, stomachache, headache and lethargy. Researchers endeavored for years to enhance the oral bioavailability, sustain the drug release for better patient compliance and reduced side effects of the most widely used oral hypoglycemic Metformin. The conventional dosage form of Metformin i.e. tablet has been modified by various approaches to get the desired results. Matrix tablets with sustained release have been prepared using hydroxypropyl methyl cellulose as a hydrophilic polymer, hydrophilic synthetic polymers and hydrophobic natural polymers and by incorporation of lipophillic waxes by melt granulation[14, 16]. With the view to enhance patient compliance taste masked tablets and oro-dispersible tablets have also been formulated, also the FDA (Food and Drug Administration) has approved metformin-glipizide tablets for oral suspension, metformin-glyburide oral solution and linagliptin-metformin hydrochloride tablets[17–19]. Niosomes are non ionic surfactant vesicles having lamellar structure formed by self assembly of surfactant molecules. To improve the oral bioavailability of poorly water soluble drug like griseofulvin, the noisome (vesicular) system was developed. In another report, the polysaccharide coated noisomes of propranolol HCl was developed for the oral drug delivery and studied the effect of polysaccharide cap using hydrophobic anchors on the non ionic surfactant vesicles. The only novel delivery system so far utilized for the delivery of metformin is mucoadhesive ispaghula-sodium alginate beads. Niosomes have been used to deliver a number of drugs and have shown pronounced benefits of enhanced bioavailability, sustained release, targeted delivery, decreased side effects, high stability, easy modification, and so on. In the present investigation niosomes have been prepared to enhance oral bioavailability of class III antidiabetic drug. The nonionic surfactant vesicles have been prepared and evaluated for entrapment efficiency, in vitro drug release, particle size, zeta potential, TEM. Also the effect of various parameters viz. molar concentration and molar ratio of cholesterol and surfactant, presence of DCP and volume of hydration was studied on the various evaluated parameters. The studied system is developed for efficient treatment of Type II diabetes.