Self emulsifying drug delivery system in solubility enhancement
- 1. Seminar on “Self emulsifying drug delivery system”
- 2. Self Emulsifying Drug Delivery System (SEEDS) has been developed to enhance the solubility of drug. Low aqueous solubility many 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 solubility/dissolution, absorption and bioavailability for poorly water soluble drug. Solubility enhancement using self emulsifying drug delivery system
- 3. SEDDS are defined as isotropic mixtures of natural or synthetic oils, solid or liquid surfactants or alternatively, one or more hydrophilic solvents & co- solvents/co-surfactants They spontaneously form emulsion on mixing with water with little or no energy input . SEDDS are solid dosage form with a unique property, that is they are able to self emulsify rapidly into fine O/W emulsion results in small droplets of oil dispersed in the gastrointestinal fluids that provide a large interfacial area enhancing the activity and minimizing the irritation. Self Emulsifying System (SES) can be formulated with little energy input .Therefore, an SES can be an efficient vehicle for class II to IV molecules of the Biopharmaceutical Classification System (BCS) drugs. Introduction of SEDDS:- Biopharmaceutics and pharmacokinetics MMCOP Pune-33 M.Pharm Sem-2
- 4. Biopharmaceutical drug classification system •gastrointestinal tract permeable. This class does not suffer from absorption or permeation problems that may affect oral drug bioavailability. •While classes II, III and IV contain drugs having problems in solubility and/or permeability that may reflect on their bioavailability in the blood after the drug is taken orally. •approximately 80% of the drugs available in the market form Classes II, III and IV.
- 5. Properties of SEDDS They are able to self emulsify rapidly in gastro-intestinal fluids & under the influence of gentle agitation provided by Peristaltic and other movements of gastro intestinal tract, they form a fine o/w emulsion. They can effectively incorporate drug (hydrophobic or hydrophilic) within the oil surfactant mixture. They can be used for liquid as well as solid dosage forms. They require lower dose of drug with respect to conventional dosage forms.
- 6. Advantages associated with SEDDS Protection of drug from GIT environment. Selective targeting of drug toward specific absorption window in GIT. Enhanced oral bioavailability. Consistent drug absorption profile. Better control of drug delivery profiles. Versatility of dosage form as can be used with liquids or solids. Drug payloads are high. Protection of sensitive drug substances
- 7. Mechanism of self emulsification Self emulsifying process are related to the free energy, ΔG given by ΔG = Σ N π r2 σ Here, N is the number of droplets with radius r and σ the interfacial energy. It is apparent from the equation that the spontaneous formation of interface between the oil and water phase is energetically not favorable. The system commonly classified as SEDDS have not yet been shown to emulsify spontaneously in the thermodynamic sense. Groves & Mustafa developed a method of quantitatively assessing the ease of emulsification by monitoring the turbidity of oil-surfactant system in aqueous system and suggested that emulsification process may be associated with the ease with which water penetrates the oil-water interface, with formation of liquid crystalline phase resulting in swelling at interface, thereby resulting in greater ease of emulsification.
- 8. Pouton has said that the emulsification capacities of surfactant may be related to phase inversion behavior of the system. If one increases the temperature of the oil in water system which is stabilized by using non-ionic surfactants, the cloud point of the surfactant will be reached followed by phase inversion. The surfactant is highly mobile at phase inversion temperature due to which o/w interfacial energy is minimized leading to a reduction in energy required for emulsification. For systems having co surfactant, separation of components between the oil and aqueous phases, may take place leading to a mechanism described as “Diffusion & Standing” whereby the oil is solubilized, leading to migration into the aqueous phase.
- 10. (A) Non-water soluble Component Systems These systems are isotropic mixtures of lipids & lipophillic surfactants having HLB value less than 12 that self emulsify to form fine oil in water emulsion in aqueous medium. Self emulsification is generally obtained at a surfactant level above 25% w/w. But at a surfactant level of 50-60% w/w the emulsification process may be formation of viscous liquid crystalline gels at the oil/water interface. This system is also known as Type-II SEDDS according to lipid formulation classification System (LFCS). These systems offer advantages - o They are able to generate large interfacial areas which cause efficient partitioning of drug between oil droplets and the aqueous phase. o They can overcome the slow dissolution step typically observed with solid dosage forms
- 11. (B) Water soluble component system These systems are formulated by using hydrophilic surfactants with HLB more than 12 & co solvents such as Ethanol, Propylene Glycol & Polyethylene glycols. Type III SEDDS are commonly known as self micro-emulsifying drug delivery systems (SMEDDS). Difference Between SEDDS and SMEDDS:- The distinction between SEDDS & SMEDDS formulation is commonly based on particle size and optical clarity of resultant dispersion. Thus SEDDS formulations typically provide opaque dispersions with particle size greater than 100 nm while SMEDDS disperse to give small droplets with particle size less than 100 nm and provide optically clear or slightly opalescent dispersions
- 12. EXCIPIENTS USED IN SEDDS FORMULATION Oil along with surfactant are necessary components, however, co surfactants may also be used.Use of other excipients in SEDDS is governed by the type of dosage form. Type of oil:- Various types of oils (natural, synthetic or semi synthetic) have been used for the formulation of SEDDS of various drugs eg. Corn oil,Olive oil,Sesame oil,Soya bean oil,Peanut oil,Bees wax, Hydrogenated soya bean oil . Generally oils with long & medium chain triglycerides with varying degrees of saturation are used for formulation of SEDDS. Edible oils without any modification provide the “Natural” base for lipid vehicles, but their poor ability to dissolve larger amount of drugs & their lower self emulsification efficiency restricts their use in SEDDS. Therefore, modified or hydrolyzed vegetable oils are preferred.
- 13. Surfactants Emulsifiers obtained from natural sources are expected to be safer than synthetic surfactants. As compared to cationic or anionic surfactants, nonionic surfactants are known to be less toxic. Nonionic surfactants with higher HLB value are preferred for formulation of SEDDS however; ethoxylated polyglycolyzed glycerides & tween 80 are the most commonly used surfactants. The concentration of surfactant in self emulsifying systems varies from 30-60% w/w of the formulation in order to prepare & maintain emulsion state in the GIT but higher concentration of surfactant may cause local irritation in the GI tract as well as moderate reversible changes in intestinal wall affecting its permeability. The surfactants being amphiphilic in nature can solubilize higher quantities of hydrophobic drug
- 14. Co solvents/Co-surfactants Generally high surfactant concentrations (usually greater than 30% w/w) are required for formulation of SEDDS. Organic solvents such as ethanol, propylene glycol, glycerol, polyethylene glycol, aids in dissolving large amount of either the drug in hydrophilic surfactants or the lipid base. These solvents also act as co-surfactant in the micro emulsion systems. It has been observed that drug release from the formulation improves with increasing amount of co surfactant .Alcohol & other volatile solvents used in the conventional self emulsifying formulations migrate into shells of capsules resulting precipitation of lipophillic drug.
- 15. Technique of solid SEDDS development Solid SEDDS were developed mainly by adsorption of solid carriers, spray drying, melt extrusion, dry emulsion, solid dispersion etc. These solid SEDDS can be converted into pellets, tablets and capsules. i) Spray Drying In this technique, first of all formulation having oil, surfactant, drug and solid carrier are sprayed into a drying chamber through a nozzle. The volatile vehicles evaporate leaving behind small solid particles which may be compressed into tablets or filled into capsules. This technique has been used to prepare dry emulsions by removing water from an ordinary emulsion. Nimodipine self micro emulsifying formulation has been prepared by spray drying technique using dextran as a solid carrier.
- 17. It shows types of solid SEDDS
- 18. EVALUATION OF SEDDS A number of tests are carried out for characterization and evaluation of SEDDS. 1. Dispersibility Test 2. Rheological Properties Determination 3. Thermodynamic stability studiesstudies i)Heating cooling cycle:ii) Centrifugation iii) Freeze thaw stress cycle 4. Robustness to dilution 5. Turbidimetric Evaluation 6. Droplet size Analysis & Particle size Measurements 7. Self Emulsification Time 8. Zeta Potential Determination 9. In vitro Diffusion Study 10. In vitro Dissolution Technique 11. Liquefaction time 12. Refractive Index (R.I.) & Percent transmittance 13. Permeation studies
- 19. REFERENCES International Journal of Pharmacy and Pharmaceutical SciencesVol 2, Suppl 1, 2010 Review ArticleNEWER APPROCHES TO SELF EMULSIFYING DRUG DELIVERY SYSTEM Indo Global Journal of Pharmaceutical Sciences, 2012; 2(3): 313-332 INDO GLOBAL JOURNAL OF PHARMACEUTICAL SCIENCES ISSN 2249- 1023