Introduction to smedds.pptx

SMEDDS consists of a mixture of drugs, oils, surfactants and co- surfactants. Gentle mixing of these ingredients in aqueous media generates micro emulsions with a droplet size in a range of 10-100 nm.

1. SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEM ( SMEDDS) Megha Assistant Professor

2. BACKGROUND The concept was first introduced by hoar and Schulman in 1940s who generated a clear single phase solution by titrating a milky emulsion with hexanol. Schulman and co-worker in 1959 subsequently coined the term microemulsion.

3. INTRODUCTION Solubility of orally administered drug is major challenge of pharmaceutical industry as nearly 35-40% of newly launched drugs possess low aqueous solubility which leads to their poor dissolution and low bioavailability, resulting in high intra and inter subject variability & lack of dose proportionality. In recent years, much attention has been focused on oral dosage forms using a self micro emulsifying drug delivery system(SMEDDS) for the purpose of improving the solubility and absorption of poorly water soluble drugs. When SMEDDS formulation is released in the lumen of the gastrointestinal tract, they come in contact with GI fluid and form a fine emulsion (micro) So called as self-emulsification which further leads to solubilization of drug that can subsequently be absorbed by lymphatic pathways , bypassing the hepatic first-pass effect. This enhancing bioavailability properties .

4. Process of self emulsifications SMEDDS

5. DEFINITION SMEDDS are defined as isotropic mixtures of natural or synthetic oils, solid and liquid surfactants” ▶ SMEDDS consists of a mixture of drugs, oils, surfactants and co- surfactants. Gentle mixing of these ingredients in aqueous media generates micro emulsions with a droplet size in a range of 10-100 nm. ▶ Resultant small droplet size from SMEDDS provides a large interfacial surface area for drug release and absorption and the specific components of SMEDDS promote the intestinal lymphatic transpor t of drugs. Thus oral absorption of certain drugs has been enhanced by SMEDDS ▶ The BCS Class II drugs has poor solubility e.g. Diclofenac, verapamil and it leads to marked improvement in absorption of Class IV drugs which have both dissolution and permeability rate limited absorption.

6. FEATURE SEDDS SMEDDS COMPOSITION Oil+ Surfactant+ Drug Oil + surfactant+ Co-surfactant+ Drug SIZE OF DROPLET 200 nm – 5 µm less than 200nm APPEARANCE Turbid in Nature Transparent in Nature THERMODYNAMICAL LY Not stable Stable PHASE DIAGRAM Ternary phase Pseudo ternary phase CON. OF OIL 40-80% less than 20% as compared to SEDDS

7. MICROEMULSION EMULSION

8. ADAVANTAGE 1. F ine oil dropl e ts of S MED D S would p a ss r a pid l y f ac i l i t a t i ng wide distribution of the drug throughout the stomach and promote wide distribution of the drug throughout the GI tract. SMEDDS are physically stable formulations. As compared with oily solutions, they provide a large interfacial area for partitioning of the drug between oil and water. Potential a dv a nta g e s of these s y stems include e nh a n ce d o r a l bio a v a i l a bi l i t y , more c onsis t e nt tempor a l p r o f i l e s o f d r u g absorption. 5. Ease of manufacture and scale- up .

9. DISADVANTAGE Dissolution of these formulations potentially are dependent on digestion prior to release of the drug. chemical instabilities of drugs and high surfactant concentrations in formulations (approximately 30-60%) which irritate GIT. Volatile co-solvents in the conventional SMEDDS formulations are known to migrate into the shells of soft or hard gelatin capsules, resulting in the precipitation of the lipophilic drugs High production costs. drug incompatibility. Drug leakage. So it may allow less drug loading.

10. COM P OSI T I ON OF SMEDDS EXCIPIENTS OI L SURFACTANT CO- SU R F A C T A NT AP I DRUG BELONG TO BCS CLASS 2

11. 1) Active pharmaceutical ingredient (API Active Pharmaceutical Ingredient (API): As, SMEDDS are used to increase the solubility of poor water-soluble drugs, BCS class II drugs are preferred e.g. itraconazole, nifedipine, vitamin E, simvastatin, danazol, ketoconazole, naproxen, carbamazepine .

12. 2 ) Oils Oils can solubilize the required dose of the lipophilic drug and facilitate self emulsification and also they can increase the fraction of lipophilic drug transported via the intestinal lymphatic system, thereby increasing absorption from the GI tract depending on the molecular nature of the triglyceride . oils drugs Market products Corn oil Valproic acid Depakene capsule Sesame oil Dronabinol Marinol soft gelatin capsule Soya bean oil Isotretinoin Accutane soft gelatin capsule Peanut oil Progesterone Prometrium soft gelatin capsule

13. 3 ) Sur f a ctant Surfactants are compounds that lower the surface tension (or interfacial tension) between two liquids, between a gas and a liquid, or between a liquid and a solid. improve the bioavailability by various mechanisms including: improved drug dissolution, increased intestinal epithelial permeability, increased tight junction permeability and decreased/inhibited p-glycoprotein drug efflux . SURFACTANTS DRUGS MARKETED PRODUCT SPAN 80,TWEEN 80 Cyclosporine Gengraf soft gelatin capsule TWEEN 20 Bexarotene Targretin Hard gelatin Capsule CREMOPHOR RH 40 Carmustine BCNU self-emulsifying implant

14. 4 ) Co-surfactants The production of an optimum SMEDDS requires relatively high concentrations (generally more than 30% w/w) of surfactants but it causes GI irritation. So co surfactant is used to reduce concentration of surfactant . Role of the co surfactant together with the surfactant is to lower the interfacial tension . EXAMPLE:- ▶ Ethanol ▶ Glycerin ▶ PEG

15. MECHANISM The free energy of the emulsion can be described by equation: Δ 𝐺 = ∑ 𝑁 Π 𝑟 2 𝜎 Δ 𝐺 is the free energy, 𝑁 is the number of droplets, 𝑟 is the radius of droplets, and 𝜎 is the interfacial energy. In SMEDDS, emulsion formation occurs instantaneously because the free energy of the system is very low and sometimes negative due to the presence of flexible interface.

16. From this equation, it is evident that the lower the Inter facial energy the lower the free energy . Self-emulsification occurs when the energy involvement in the dispersion is greater than the energy required for the formation of droplets . The free energy of conventional emulsion is very high as high energy is required to form new surface between two immiscible phases like oil and water. Due to high free energy, the emulsion may not be stable and the two phases tend to separate. But in case of SMEDDS, emulsion formation occurs instantaneously because the free energy of the system is very low and sometimes negative due to the presence of flexible interface .