Formulation and Process Challenges in Development of Solid-Self Micro Emulsifying Drug Delivery System (SMEDDS)

Abstract

Most of the recent discovery of new chemical entity are addressing the challenges of poor solubility and hence adversity in their formulation development. To counteract this crunch of formulation, as dispersion of drugs acts as a prerequisite for its absorption, lipids based systems play a viable role in acknowledging this criticality and improving the absorption of highly lipophilic drugs and further their bioavailability through its lymphatic pathway. Recent work on SEDDS lack industrial scalability, deficits patient compliance and becomes uneconomical on commercial scale. The present study focuses on the development of a self-micro emulsifying drug delivery system of a BCS class II drug using QbD approach and the process challenges involved while its formulation and characterization. Conventional preparation of lipid formulations is typically in liquid form which possesses certain drawbacks. To step up over those drawbacks and improve the efficacy as well as stability of dosage form, solid lipid formulations are augmenting popularity in recent years- however it is less explored in public domain. This research work also targets the challenges encountered in formulation of liquid SMEDDS into its solid form. The selection of excipients is done on the basis of solubility study and the ratios are optimized with the help of pseudo ternary diagrams. High shear granulation technique was selected for solidifying liquid SMEDDS. The study focuses on the QbD aspects i.e. Critical Material Attributes (CMA’s) and Critical Process Parameters (CPP’s) involved in development of solid SMEDDS of selected drug. Various trials were performed to form tablets with desired characteristics. An optimized formulation was obtained using Capmul MCM C8 as an oil, Polysorbate 80 as a surfactant, PEG 200 as a co-solvent, Neusilin US2 as an adsorbent, Ceolus-702 as a filler, Ceolus KG-1000 used for increasing compressibility, Starch 1500 as a binder and Magnesium Stearate as a lubricant. The stability study for three months was conducted for liquid SMEDDS and one month stability study for SMEDDS tablet which concludes that the SMEDDS formed are stable in liquid state as well as in form of tablets. In conclusion, SMEDDS of selected model drug showed improved solubility. Thus it could be predicted that the developed formulation maybe effective in treatment of hypertension. However in-vivo studies will give better results.