Self emulsifying drug delivery system

Self emulsifying drug delivery system

1. Self-emulsifying drug delivery systems Presented by: Gaurav

2. INTRODUCTION Self emulsifying drug delivery system (SEDDS) are defined as isotropic mixtures of oil, surfactant & co-surfactant

3. Need of SEDDS Around 40% of new Drug shows poor aqueous solubility and poor bioavailability. For BCS class II drugs (Low Solubility & High permeability) Selective targeting of drugs toward specific absorption window in GIT. Examples of BCS class II drugs: Acetylsalicylic acid, Ibuprofen, Captopril

4. Act on Body ? SEDDS emulsify spontaneously to produce fine oil in water emulsions when introduced into aqueous phase under gentle agitation (by peristaltic movement) and absorb by lymphatic pathways. SEDDS produce emulsions with a droplets size 100 to 300 nm while SMEDDS form transparent nano-emulsions with a size 50 nm and less.

5. Components for SEDDS 1. Oil Help in solubilizing the lipophilic drug in high amount. Facilitate self emulsification. Increase the fraction of lipophilic drug transported. Increase absorption from GI track Examples:- Corn oil Olive oil Soyabean oil Peanut oil Palm seed oil Mixture of mono & di- glycerides

6. 2. Surfactants Non- ionic surfactants with high hydrophilic-lipophilic balance (HLB) value are used in SEDDS formulations. Surfactant concentration should be 30-60% w/w for the stable formulation. Higher concentration may irritate GIT. Examples:- -Polysorbate 20 (Tween 20) - Sorbitan monooleate (Span 80) -Polysorbate 80 (Tween 80) -Cremophor

7. 3. Co- Surfactants Co-Surfactant help to dissolve large amount of hydrophilic surfactants or hydrophobic drug in lipid base. Co- Surfactant plays an important role in micro emulsion systems. Drug release is increased with increasing co-surfactant concentration in formulation. Examples of Co-surfactant: Polyethylene glycol, Glycerin , Propylene glycol.

8. Mechanism of Self Emulsification The free energy of the conventional emulsion is a direct function of the energy required to create a new surface between the oil and water phases. Free energy in the micro- emulsion formulation is directly proportional to the energy required to create new surface between the two phases and given by equation. ∆ G = ∑N π r ² σ Where, ∆ G= Free energy associated with the process. N : Number of droplets R : Radious of droplets σ : Int erfacial energy

9. Types of dosage form As SEDDS may exist in liquid or solid dosage form, but due to better stability as well as easy in handling and transportation. Solid self emulsifying drug delivery system are generally preferred over liquid SEDDS.

10. Method of Solidification Spray Drying Formulation contain oil, surfactant drug & other solid carriers are sprayed into a drying chamber through a nozzle. The volatile vehicle evaporate & leaving behind small solid particles. This technique is use for preparation of dry emulsion by removing water from an ordinary emulsion.

11. 2. Spray Cooling Molten formulation is sprayed into cooling chamber. When this molten mixture comes in contact with cool air, the molten droplets recrystallize into solid particles which collect into the bottom of chamber in the form of fine powder. 3. Melt Extrusion Based on the property of materials which can be easily extruded and spheronized . This technique do not require liquid excipients although constant temp and pressure has to be maintained to achieve high drug loading.

12. Evaluation of SEDDS Thermodynamim stability studies. a) Centrifugation b) Freeze thaw cycle c) Heating cooling cycle 2. Dispersibility test 3. Turbidimetric evaluation 4. Viscosity determination 5. Particle size 6. In-Vitro diffusion study 7. In-Vivo permeability studies

13. Marketed preparation Drug Brand Name Company Formulation Indication Cyclosporin A Sandimmun   Neoral Novartis Soft gelatin capsule Immuno- suppressant Ritonavir Norvir Abbott Soft gelatin capsule HIV Antiviral Sanquinavir Fortovase Roche Soft gelatin capsule HIV antiviral Valporic acid Convulex Pharmacia Soft gelatin capsule Antiepileptic Amprenavir Agenerase Glaxo Smithkline Soft gelatin capsule HIV antiviral Calcitrol Rocaltrol Roche Soft gelatin capsule Calcium regulator

14. Title: Development and in vitro Evaluation of Gastro-protective Aceclofenac -loaded Self-emulsifying Drug Delivery System Journal: International Journal of nanomedicine Impact factor: 4.47

15. Material OIL = Oleic acid surfactant =Tween 80, Kolliphor EL co-surfactant = PEG 400, Propylene glycol All excipients are selected on the basis of solubility study of Aceclofenac

16. Formulation Surfactant Co-Surfactant Oil Smix Surfactant: co-surfactant 1:1, 2:1, 3:1 Smix : Oil 1:1 to 1:2 Stirred slowly avoid bubble Group 1: Oleic acid, Tween 80 & PEG 400 Group 2: Oleic acid, Kolliphor EL & PG

17. Aceclofenac loaded SEDDS The entrapment efficiency of formulation F3 shown higher 76%. Least entrapment efficacy was 73.1% of formulation F4 .

18. Particle size The average globular size ranged between 111.3 nm to 470.2 nm. The smallest size was shown in formulation F2 ( 111.3 nm ).

19. Thermodynamic stability studies All ACF-SEDDS formulations showed no sign of precipitation, cloudiness or separation. These data ensure the stability of all SEDDS formulations on different temperature and environment fluctuation

20. In-Vivo study In-vitro release study were carried out in SGF & SIF. Along with ACF suspension as control.. In first 2 hrs of study ACF release was 24.81% (SGF) & 2.43% (SIF) Drug release in SGF was significantly low. Formulation 2 Hrs 4 Hrs 6 Hrs F1 74% 98.13 - F2 95% - 97.75% F3 88.15% - 98.13% F4 95.83 - 95.73%

21. Result summary Formulation Composition Entrapment Drug Loading Particle Size Thermodynamic stability Drug release in SIF F1 T80- PEG (1:9) 75.13 % 6.76 % 244.6 nm 98.13% (4 hrs) F2 T80 – PEG (1:8) 73.20 % 7.33 % 111.3 nm 97.75% (6 hrs) F3 KEL – PG (1:9) 76.00 % 6.60 % 389.4 nm 98.83% (6 hrs) F4 KEL – PG (1:8) 73.10 % 7.32 % 470.9 nm 95.73% (6 hrs)

22. Conclusion All the formulations are thermodynamically stable Formulations shows high emulsification in short period of time Tween-80 & Kolliphor shows reduce drug release in SGF but higher in SIF ACF-SEDDS would be promising system for improve solubility of lipophilic drugs

23. References Jianxian C, Saleem K, Ijaz M, Ur-Rehman M, Murtaza G, Asim MH. Development and in vitro Evaluation of Gastro-protective Aceclofenac -loaded Self-emulsifying Drug Delivery System. International Journal of Nanomedicine. 2020;15:5217. Jaiswal P, Aggarwal G. Bioavailability enhancdement of poorly soluble drugs by smedds : a review. Journal of drug delivery and therapeutics. 2013 Jan 14;3(1). Maurya SD, Arya RK, Rajpal G, Dhakar RC. Self-micro emulsifying drug delivery systems (SMEDDS): a review on physico -chemical and biopharmaceutical aspects. Journal of Drug Delivery and Therapeutics. 2017 May 14;7(3):55-65. Kyatanwar AU, Jadhav KR, Kadam VJ. Self micro-emulsifying drug delivery system (SMEDDS). Journal of Pharmacy Research. 2010 Jan;3(2):75-83. Savale S, Chalikwar S. Self-Micro Emulsifying Drug Delivery System (SMEDDS): A Review. Asian Journal of Biomaterial Research. 2017;3(2):12-7. Sanghai B, Aggarwal G, HariKumar SL. Solid self microemulsifying drug deliviry system: a review. Journal of Drug Delivery and Therapeutics. 2013 May 13;3(3):168-74.