Low aqueous solubility and thereby low oral bioavailability is a major concern for formulation scientist as many recent drugs are lipophillic in nature and their lower solubility and dissolution is a major drawback for their successful formulation into oral dosage forms. Aqueous solubility of drugs can be increased by different methods such as salt formation, solid dispersion, complex formation but Self Emulsifying Drug Delivery System (SEDDS) is gaining more attention for improving the solubility of lipophillic drugs enabling reduction in dose. SEDDS is ideally isotropic mixtures of drug, oil, surfactant and/or co surfactant. This becomes emulsify when come in contact with aqueous solution of GIT under the condition of gentle stirring and digestive motility. Generally SEDDS are prepared using triglycerides and non ionic surfactants. SEDDS includes various dosage forms like capsule, tablets, beads, microspheres, nanospheres, etc. Thus SEDDS could efficiently improve oral absorption of the sparingly soluble drugs by self-emulsification. SEDDS is evaluated by various methods like visual assessment, droplet polarity and droplet size, size of emulsion droplet, dissolution test, and charge of oil droplets, viscosity determination, and in-vitro diffusion study. With future development of this technology, SEDDS will continue to enable novel applications in drug delivery and solve problems associated with the delivery of poorly soluble drugs like BCS class II. Purpose of this project is to provide brief outline of self emulsifying drug delivery system & an updated account of the advancements in SEDDS with regard to the selection of lipid systems for current formulations, dosage forms for SEDDS, solidification techniques, characterization and their applications.
Successful treatment of most of the diseases is limited by a lack of safe and effective methods of drug delivery. The oral route is the most preferred route of drug delivery by the patients as well as the manufacturers for the treatment of most pathological states. Nearly 35 to 40% of newly launched drugs possess low aqueous solubility which leads to their poor dissolution and thereby low bioavailability, resulting in high intra & inter subject variability & lack of dose proportionality (Amidon et al., 1995). For these drugs absorption rate from gastrointestinal tract is mainly governed by dissolution and improvement in solubility may lead to enhanced bioavailability (Katteboina et al., 2009; Pouton, 1997). Besides, oral bioavailability also depends upon a multitude of other drug factors such as stability in GI fluids, (O'Driscoll and Griffin, 2008) intestinal permeability, resistance to metabolism by cytochrome P450 family of enzymes present in gut enterocytes and liver hepatocytes, and interaction with efflux transporter systems like P-glycoprotein (P-gp) (Constantinides and Wasan, 2007).
There are number of techniques to overcome such problems arising out of low solubility and bioavailability, which may result into improved therapeutic efficacy of these drugs. The techniques like complex formation with cyclodextrins, solid dispersion, liposome formation, co precipitation, micronization, salt formation, use of permeation enhancer, use of micelles, co grinding and emulsification had been used for improving the dissolution profile of drugs with low solubility (Shaji and Jadhav, 2010).
The molecular characteristics of BCS class II drugs are identified as low solubility and high permeability. For instance, cyclosporine, griseofulvin and itraconazole are categorized into this class (Wu and Benet, 2005). Generally, the bioavailability of a BCS class II drug is rate-limited by its dissolution, so that even a small increase in dissolution rate sometimes results in a large increase in bioavailability (Lobenberg and Amidon, 2000). Therefore, an enhancement of the dissolution rate of the drug is thought to be a key factor for improving the bioavailability of BCS class II drugs. Several physicochemical factors control the dissolution rate of the drugs. According to the modification of the Noyes-Whitney equation, the factors affecting the drug dissolution rate are defined as the effective surface area, the diffusion coefficient, the diffusion layer thickness, the saturation solubility, the amount of dissolved drug, and the volume of dissolution media (Aungst, 1993). Increases in the saturation solubility and the effective surface area have a positive impact on the dissolution rate of the drugs, and these factors could be increased by efforts of preformulation study and formulation design. Crystal modification, particle size reduction, pH modification and amorphization (Horter and Dressman, 2001) are considered to be effective for improving the dissolution behavior of BCS class II drugs.
Self-emulsifying drug delivery systems (SEDDS) are relatively newer lipid-based technological innovations with immense promise in oral bioavailability enhancement of lipophilic drugs. SEDDS are defined as isotropic mixtures of drug, natural or synthetic oils, solid or liquid surfactants or alternatively, one or more hydrophilic solvents & co-solvents/co-surfactants that have a unique ability of forming fine oil-in-water (o/w) microemulsions upon mild agitation followed by dilution in aquous media, such as GI fluids (Katteboina et al., 2009). The resultant small droplet size from SEDDS provides a large interfacial surface area for drug release and absorption, and the specific components of SEDDS promote the intestinal lymphatic transport of drugs. Verily, SEDDS is a broad term typically producing emulsions with a droplet size ranging between a few nanometers to several microns. Depending upon the size of globules, they are basically the concentrated microemulsions, nanoemulsions or their pre-concentrates (Joshi et al., 2008). Self-microemulsified drug delivery system (SMEDDS) indicates the formulations forming transparent microemulsions with the oil droplet size range between 100 and 250 nm. Self-nanoemulsified drug delivery system (SNEDDS) is relatively a recent term indicating the globule size less than 100 nm (Pouton and Porter, 2008).
Successful treatment of most of the diseases is limited by a lack of safe and effective methods of drug delivery. The oral route is the most preferred route of drug delivery by the patients as well as the manufacturers for the treatment of most pathological states. Nearly 35 to 40% of newly launched drugs possess low aqueous solubility which leads to their poor dissolution and thereby low bioavailability, resulting in high intra & inter subject variability & lack of dose proportionality (Amidon et al., 1995). For these drugs absorption rate from gastrointestinal tract is mainly governed by dissolution and improvement in solubility may lead to enhanced bioavailability (Katteboina et al., 2009; Pouton, 1997). Besides, oral bioavailability also depends upon a multitude of other drug factors such as stability in GI fluids, (O'Driscoll and Griffin, 2008) intestinal permeability, resistance to metabolism by cytochrome P450 family of enzymes present in gut enterocytes and liver hepatocytes, and interaction with efflux transporter systems like P-glycoprotein (P-gp) (Constantinides and Wasan, 2007).
There are number of techniques to overcome such problems arising out of low solubility and bioavailability, which may result into improved therapeutic efficacy of these drugs. The techniques like complex formation with cyclodextrins, solid dispersion, liposome formation, co precipitation, micronization, salt formation, use of permeation enhancer, use of micelles, co grinding and emulsification had been used for improving the dissolution profile of drugs with low solubility (Shaji and Jadhav, 2010).
The molecular characteristics of BCS class II drugs are identified as low solubility and high permeability. For instance, cyclosporine, griseofulvin and itraconazole are categorized into this class (Wu and Benet, 2005). Generally, the bioavailability of a BCS class II drug is rate-limited by its dissolution, so that even a small increase in dissolution rate sometimes results in a large increase in bioavailability (Lobenberg and Amidon, 2000). Therefore, an enhancement of the dissolution rate of the drug is thought to be a key factor for improving the bioavailability of BCS class II drugs. Several physicochemical factors control the dissolution rate of the drugs. According to the modification of the Noyes-Whitney equation, the factors affecting the drug dissolution rate are defined as the effective surface area, the diffusion coefficient, the diffusion layer thickness, the saturation solubility, the amount of dissolved drug, and the volume of dissolution media (Aungst, 1993). Increases in the saturation solubility and the effective surface area have a positive impact on the dissolution rate of the drugs, and these factors could be increased by efforts of preformulation study and formulation design. Crystal modification, particle size reduction, pH modification and amorphization (Horter and Dressman, 2001) are considered to be effective for improving the dissolution behavior of BCS class II drugs.
Self-emulsifying drug delivery systems (SEDDS) are relatively newer lipid-based technological innovations with immense promise in oral bioavailability enhancement of lipophilic drugs. SEDDS are defined as isotropic mixtures of drug, natural or synthetic oils, solid or liquid surfactants or alternatively, one or more hydrophilic solvents & co-solvents/co-surfactants that have a unique ability of forming fine oil-in-water (o/w) microemulsions upon mild agitation followed by dilution in aquous media, such as GI fluids (Katteboina et al., 2009). The resultant small droplet size from SEDDS provides a large interfacial surface area for drug release and absorption, and the specific components of SEDDS promote the intestinal lymphatic transport of drugs. Verily, SEDDS is a broad term typically producing emulsions with a droplet size ranging between a few nanometers to several microns. Depending upon the size of globules, they are basically the concentrated microemulsions, nanoemulsions or their pre-concentrates (Joshi et al., 2008). Self-microemulsified drug delivery system (SMEDDS) indicates the formulations forming transparent microemulsions with the oil droplet size range between 100 and 250 nm. Self-nanoemulsified drug delivery system (SNEDDS) is relatively a recent term indicating the globule size less than 100 nm (Pouton and Porter, 2008).
No comments:
Post a Comment