SELF MICROEMULSIFYING DRUG DELIVERY SYSTEM : SELF MICROEMULSIFYING DRUG DELIVERY SYSTEM INTRODUCTION :
1. Self micro emulsifying drug delivery system (SMEDDS) or self micro emulsifying oil formulation is defined as the isotropic mixtures of oil and surfactants or one or more hydrophilic solvents and co-solvents.
2.Upon mild agitation followed by dilution in aq media such as Gastrointestinal (GI) fluid , these systems form fine oil in water (o/w) emulsions or micro emulsions i.e SMEDDS. Slide 2: 3. Self micro emulsifying formulations spread readily in the GI tract & the digestive motility of the stomach & intestine provide the agitation necessary for self emulsification.
4. Self emulsifying drug delivery systems(SEDDS) produce emulsions with a droplet size between 100 -300 nm while SMEEDS form transparent micro emulsions with a droplet size of less than 50 nm.
5. SEDDS & SMEDDS are physically stable formulations and are easy to manufacture. Slide 3: 6. SMEDDS can be formulated to give sustained release dosage form by adding polymeric matrix which is non ionizable at physiological pH & after ingestion in contact with GI fluids forms a gelled polymer making it possible to release the micro emulsified agent in a continuous & sustained matter by diffusion.
7. Bases of self micro emulsifying system have been formulated using medium chain triglyceride oils & non ionic surfactant which are acceptable for oral ingestion. Slide 4: 8.The lipophilic (poorly water soluble) drugs such as nifedipine,cyclosporin,digoxin,ibuprofen,carbamazepine,steroids,diazepam, etc. are formulated in SMEDDS to improve efficacy & safety.
9.This system can be liquid but also semisolid depending on the excipient’s choice. These are designed traditionally for oral route.
10.These preparations can be give as soft/hard gelatin capsules for easy administration & precise dosage. FORMULATION OF SMEDDS : : FORMULATION OF SMEDDS : 1. Drugs with low aq solubility present a major challenge during formulation as their high hydrophobicity prevents them from being dissolved in most approved solvents.
2. The novel synthetic hydrophilic oils & surfactants usually dissolve hydrophobic drugs to a greater extent than conventional vegetable oils.
3. The addition of solvents such as ethanol,PG, & PEG may also contribute to the improvement of drug solubility in the lipid vehicle. Slide 6: The following should be considered in the formulation of SMEDDS :
1 : The solubility of the drug in different oils , surfactants , co solvents.
2 : The selection of oil, surfactant and co solvent based on the solubility of the drug.
3 : Preparation of the phase diagram.
4 : The preparation of SMEDDS formulation by dissolving the drug in a mixture of oil, surfactant & co solvent. COMPOSITION : : COMPOSITION : 1. Oils
3.Co solvents/Co surfactants OILS : : OILS : The oils represent the most important excepient in the SMEEDS formulation.It can solubilize relevant amount of the poorly water soluble drug. Both long chain trigyceride (LCT) and medium chain triglyceride(MCT) oils with different degrees of saturation have been used in in the design of SMEDDS.
E.g.- Corn oil, soybean oil, hydrolysed corn oil. SURFACTANTS : SURFACTANTS Surfactant molecules can be classified based on the nature of hydrophilic group within the moleecule. The four main group of surfactants are defined as follows,
4.Nonionic surfactants Slide 10: 1 . Anionic surfactants, where the hydrophilic group carries a negative charge such as carboxyl(RCOO-),sulphonate(RSO3-) or sulphate(ROSO3-).
E.g: Potassium laurate, sodium lauryl sulphate.
2. Cationic surfactants where the hydrophlic group carries a positive charge.
E.g: Quarternary ammonium halide.
3. Ampholytic ( zwitterionic) surfactants contain both positive & a negative charge.
E.g: Sulfobetaines . Slide 11: 4. Nonionic surfactants, where the hydrophilic group carries no charge but derives its water solubility fro highly polar groups such as hydroxyl or polyoxyethylene(OCH2CH2O).
E.g.: Sorbitan esters(spans),polysorbates (Tweens).
Nonionic surfactants with high hydrophilic lipophilic balance(HLB) values are used in the formulation of SMEDDS. The usual surfactant strength ranges between 30-60% w/w of the formulation in order to form a stable SMEDDS. COSOLVENTS : COSOLVENTS Organic solvents such as ethanol,propylene glycol(PG) and polyethylene glycol(PEG) are suitable for oral delivery and they enable the dissolution of large quantities of either the hydrophilic surfactant or the drug in the lipid base.
These solvents can even act as as co surfactants micro emulsion systems. OTHER COMPONENTS : : OTHER COMPONENTS : These may be pH adjusters, flavors,and antioxidant agents. Lipophilic antioxidants(E.g. alpha tocopherol, propyl gallate,ascorbyl palmitate ) may be required to stabilize the oily content of SMEDDS formulation. CHARACTERIZATION OF SMEEDS : CHARACTERIZATION OF SMEEDS Physical Appearance
Particle Size Determination
Photon Correlation Spectroscopy
Transmission Electron Microscopy
Scanning Electron Microscopy Slide 15: Polarised Light Microscopy