Studies On Piroxicam Self Micro-Emulsifying DDS

The enhancement of oral bioavailability of poorly water soluble active pharmaceutical ingredients (APIs) or new chemical entities (NCEs) remains one of the most challenging aspects of drug development. Although salt formation, solid dispersion, cyclodextrin inclusion, liposome, solubilisation and micronization have commonly been used to enhance the in vitro dissolution rate and thereby oral absorption and bioavailability, there are practical difficulties. The use of very fine powders may still be problematic to handle due to poor wettability. Lipid-based drug delivery systems have gained an important place in the formulation of poorly soluble drugs for oral administration. Lipid-based formulations are typically administered in liquid form, generally in soft-gel capsules. This can offer favorable dissolution, release, and bioavailability properties. Self emulsifying drug deliver system (SEDDS) and self micro-emulsifying drug deliver system (SMEDDS) is one of the technologies to improve poorly water soluble APIs or NCEs wettability, dissolution rate, bioavailability.There are a number of characteristics of lipid-based delivery systems which make them an important tool to formulate drugs with dissolution-rate limited absorption. Advantages include solubilisation of hydrophobic drugs in the lipid matrix, absorption enhancement, and avoidance of the food effect. Components of these formulations include triglycerides, which can be long chain (14-18 carbons), or medium chain (6-12). The latter are less viscous and generally have higher solubilisation ability than long chain analogues. Mono-/diglycerides are more hydrophilic than corresponding triglycerides, and have higher solubilisation ability and dispersibility. Fatty acids (e.g. oleic acid), co-solvents, and surfactants may also be important components of lipid-based formulations. Surfactants can be categorised into either high hydrophilic-lipophilic balance (HLB), such as polysorbates, polyoxyl castor oils (Cremophor(?)), Gelucire(?) 44/14, Labrasol(?), poloxamers, and Vitamin E TPGS, or low HLB (e.g. SPAN(?), Labrafil(?), lecithins); both high and low HLB surfactants are useful in formulating lipid-based drug delivery systems. When added to water, those with higher levels of surfactants and co-solvents will disperse into smaller droplet size, which will aid absorption of drugs in the intestinal lumen due to the larger available droplet surface area. Nevertheless, even those lipid formulations with low surfactant and cosolvent content (and thus relatively large initial droplet size after dispersion) will often afford adequate absorption of poorly soluble drugs. This is due to the fact that in the gastrointestinal (GI) tract, triglycerides will be digested by lipases into mono- and di-glycerides, glycerol, and fatty acids, which will themselves act as surfactants and reduce the particle size. These will be further solubilised by bile salts and phospholipids to form mixed micelles of low particle size, favoring partitioning and diffusion of drug molecules to the surface of the enterocytes for absorption. The process of digestion is crucial for drug absorption for lipid formulations with low surfactant content, while those with high surfactant and co-solvent content will have less dependence on digestion products for their emulsification. A useful tool for understanding the phase structure and properties of lipid-based drug delivery systems is the phase diagram . The types of structures formed can be identified as a function of oil/surfactant/water ratios. This will aid in understanding changes encountered over the dilution path, and thus serve as a tool for choosing the formulation composition .This paper presents the use of vehicle/excipient screening for judicious selection of type and concentration of each excipient in formulating a SMEDDS of a poorly soluble drug (Piroxicam). This paper will outline the general concepts of solubilisation and bioavailability enhancement with lipid-based formulations; compare liquid and solid dosage forms. Finally, chemical and physical stability considerations for lipid-based drug delivery systems will be discussed. The pros and cons of the various approaches for lipid-based formulations will be outlined in order to guide the formulator in choosing an appropriate dosage form based on drug profile and application requirements. The dissolution rate and particle size of Piroxicam SMEDDS was evaluated in vitro. The bioavailability of Piroxicam SMEDDS in rabbit showed 4.8 times Cmax and 466% bioavailability compared with suspention dosage form.