Emulsion & SMEDDS

EMULSION and SMEDDS topics are covered .

1. EMULSION AND SMEDDS SEPARATION AND STABILITY Presented by – Guided by - AKASH DOMALE Dr. Abhijeet D Kulkarni Sir Roll no – 02 Sanjivani College of Pharmaceutical Education and Research

2. CONTENTS DEFINATION BACKGROUND INTRODUCTION DIFFRENCE BETWEEN EMULSION AND MICROEMULSION FORMULATION STABILITY MARKETED PREPARATION

3. EMULSION : Emulsion is mixture of two or more liquid that are normally immiscible SMEDDS : SMEDDS are defined as isotropic mixtures of natural or synthetic oils, solid and liquid surfactants. DEFINITIONS

4. Types of self microemulsion o/w micro emulsion 2 .w/o micro emulsion

5. BACKGROUND Concept introduced by hoar and schulman in 1940’s who generated a clear single phase solution by titrating a milky emulsion with hexanol alternative names for these systems are often used such as transparent emulsion ,swollen micelle,micellar solution and solubilized oil. Schulman and co worker in 1959 subsequently coined the term microemulsion.

6. In recent years , much attention has been focused on oral dosage form using a self micro-emulsifying drug delivery system [SMEDDS] for the purpose of improving the solubilityAnd absorption of poorly water soluble drug SMEDDS consists of a mixture of drug, oils ,surfactants and other additives gentle mixing of these ingredients in aqueous media generates microemulsion with droplet size in a range of 10-100nm SMEDDS has been shown to improve absorption of drugs by rapid self micro emulsification in the stomach ,with the micro emulsion droplets subsequently dispersing in the gastrointestinal tract to reach site of absorption INTRODUCTION SMEDDS

7. Emulsion Emulsion consists of roughly spherical droplets of one phase dispersed to other. They are non transparent as the particle/droplet size varies from 1-20mm. Formulation requires shaking. They are thermodynamically unstable. They are various formulation. they are lyophobic. They constantly evolve between various structures ranging from droplet to bi continuous structure They are transparent as the particle/ droplet size is only 10-100nm. It is constant formulation. They are thermodynamically stable. They can accommodate 20-40% without increase in viscosity. They are on the borderline between lyophobic and lyophilic colloids . Microemulsion

8. Composition of SMEDDS formulation Typically, a SMEDDS formulation comprises of drug, oil, surfactant and co-surfactant Drug Lipophilicity and dose of the drug are the main criteria to be considered before development of SMEDDS formulation. Ideally, drug should have low dose, log P 2 and should not possess extensive first pass metabolism. The drug should show substantial solubility in pharmaceutically accepted lipids, surfactants and co-solvents

9. Oils Medium chain triglycerides (MCT) having carbon atoms between 6 and 12 are directly transported by portal blood to the systemic circulation. Whereas, long chain triglycerides (LCT) having carbon atoms greater than 12 are transported via intestinal lymphatics. As MCT have higher solvent capacity and are also not subjected to oxidation, they are widely used in lipid based formulations Oils

10. Surfactants form the interfacial film and lower the interfacial tension to a small value which facilitates dispersion process. HLB value and concentration of surfactant is essential to be considered while selecting a surfactant. For attaining high emulsifying performance, the emulsifier involved in the formulation of SMEDDS should have high HLB greater than 12 which assists in formation of small o/w droplets and rapid spreading of formulation in aqueous media. Generally, non-ionic surfactants with HLB412 are suggested for design of self-dispersing systems as these are less toxic than ionic surfactants Surfactants

11. Co-surfactants ensures flexibility of the interfacial layer, i.e. it reduces the interfacial tension to a negative value. Co-surfactants form a flexible interfacial film in order to acquire different curvatures required to form microemulsion over a wide range of composition. Medium chain length alcohols (C3–C8) are commonly employed as co-surfactants CO-SURFACTANTS

12. Oil Phase • Isopropyl Myristate • Oleic acid • Olive oil • Mineral oil • Medium chain triglyceride • Soyabean oil • Captex 355 • Isopropyl Palmitate • Sunflower oil • Safflower oil Co-surfactant • Propylene glycol • Ethylene glycol • Ethanol • 1-butanol • Isopropyl alcohol • PEG 600 • Glycerol • PEG 400 Surfactant • Tween 80 • Tween 40 • Span 40 • Labrafil M1944CS • Polyoxyethylene-35- ricinoleate • Brij 58 • CremophorEL • Lecithin EXAMPLE

13. Preparation of Smedds

14. (1) Storage : SMEDDS has the same advantage as emulsions, of facilitating the solubility of hydrophobic drugs. Microemulsions undergo creaming over a period of time, whereas SMEDDS being thermodynamically stable can be stored easily (2) Stability : In contrast to micro/ nanoemulsions , SMEDDS do not contain water and hence, they have improved physical and/or chemical stability on long-term storage. Self-nanoemulsifying tablets of carvedilol showed successful incorporation of carvedilol within the SNEDDS. This resulted in improvement of the stability of carvedilol on dilution with aqueous media in the presence of cellulosic polymers (3)Compliance : Most of the SMEDDS formulations are in capsule or tablet dosage forms, thus occupying smaller volume, easy to administer and hence improved patient compliance ( Advantages

15. (1) Drug precipitation on dilution: Diluted SMEDDS undergo precipitation of drug in gastrointestinal fluid. A common requirement for the lipid formulations is that they should be able to keep the drug in the solubilized form in the gastrointestinal tract (GIT). Precipitation of the drug from the system nullifies the advantage offered by the lipid-based formulation system. (2) The precipitation tendency of the drug on dilution is higher due to the dilution effect of the hydrophilic solvent. It thereby requires incorporation of polymers to minimize drug precipitation. (3)Storage and handling: Liquid SMEDDS exhibit problems in handling, storage and stability. Thus, formulating solid SMEDDS seems to be a logical solution to address these problems. DISADVANTAGE

16. Thermodynamic Stability Studies These studies are useful to evaluate the consequence of temperature change on formulation. Formulation is diluted with aqueous phase and subjected to centrifugation at 15,000 rpm for 15 min or at 3500 rpm for 30 min . The samples in which the phase separation is not observed are subjected to freeze thaw cycles (−20°C and 40°C temperature, resp.) and observed visually. The thermodynamically stable formulations will not show any change in visual description . .

17. In Vitro Dissolution Profile Drug release from formulation can be evaluated after filling the formulation in a hard gelatin capsule using USP XXIII apparatus I at 100 rpm [44, 64, 65] or USPXXIII apparatus II at 50 rpm or with dialysis method [66] at °C. Samples at regular intervals should be withdrawn from the medium and drug content is estimated and compared with the control. The polarity of oil droplet has impact on drug release from the diluted SMEDDS. The higher the polarity, the faster the drug release from the oil droplet into the aqueous phase. Polarity is mainly dependent on the HLB of surfactant, molecular weight of hydrophilic part of the surfactant, and its concentration along with the degree of unsaturation of fatty acid of lipid phase

18. 6.4.16. Stability Assessment Stability studies are performed as per the ICH guidelines on the formulation which is filled in gelatin capsules. At regular intervals the samples should be collected and tested for appearance, color , drug content, pH of diluted formulation, and dissolution profile. If there is no change in all these properties during storage conditions, formulation can be concluded as stable formulation

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