Self-emulsifying pellets (SEPs) of Atorvastatin Calcium (AtrCa) were developed and processed into tablets (SETs). Self-emulsifying drug delivery system (SEDDS) composed of oleic acid, Tween 20, Span 80 and N-Methyl-2-pyrolidone gave great solubility improvement and was used as oil in water emulsion for the preparation of SEPs. Due to the high 60% w/w SEDDS content required to achieve a therapeutic dose in the final tablet form, sonication was necessary to improve fluidity and stability. Colloidal silicon dioxide (CSD) and microcrystalline cellulose (MCC) were the solids in the pellet formulation employed at a ratio 7:3, which enabled production of pellets with high SEDDS content and acceptable friability as well. Emulsions were characterized physico-chemically, SEPs for physical properties and reconstitution, and tablets of compressed pellets for mechanical strength, disintegration into pellets and drug release. SEPs compressed with 30% MCC at 60 MPa gave tablets of adequate strength that disintegrated rapidly into pellets within 1 min. Emulsion reconstitution took longer than drug release due to adsorption of SEDDS on CSD, implying dissolution at the pellet surface in parallel to that from the dispersed droplets. Compared to the commercial tablet, drug release from the self-emulsifying forms was faster at pH 1.2 where the drug solubility is poor, but slower at pH 6.8 where the solubility is higher. Permeability and cytotoxicity were also studied using Caco-2 cells. The results showed that drug transport from the apical to basolateral compartment of the test well was 1.27 times greater for SEPs than commercial tablets, but 0.86 times lower in the opposite direction. Statistical analysis confirmed the significance of these results. Toxicity was slightly reduced. Therefore, the increased permeability in conjunction with the protection of the drug being dissolved in the SEDDS droplets, may reduce the overall effect of presystemic metabolism and enhance bioavailability.

Objective: The aim of this study was to develop a new dosage form as an alternative to the classical tablet forms of atorvastatin calcium (AtrCa). The formulation strategy was to prepare an optimum self micro emulsifying drug delivery system (SMEDDS) to overcome the problem of low solubility of the active substance. Methods: In this study, pseudo ternary phase diagrams were plotted determined by the solubility studies. According to the solubility studies; oleic acid was used as the oil phase, Tween 20 and Span 80 were used as the surfactants and ethanol was used as the co-surfactant. SMEDDS formulations were characterized according to pH, electrical conductivity, density, refractive index, viscosity, emulsification time, dispersibility, robustness of dilution stability, droplet size, polidispersity index, zeta potential, transmittance %, cloud point, content quantification %, chemical and physical stability. The lipolysis study was conducted under fed and fasted conditions. In vitro release studies and kinetic evaluation were carried out. Permeability studies were also examined with Caco-2 cell culture. Results: The droplet size of the optimized formulation did not change significantly in different medias over the test time period. Improved SMEDDS formulation will progress steadily without precipitating along the gastrointestinal tract. Lipolysis studies showed that the oil solution had been exposed to high amount of lipolysis compared to the SMEDDS formulation. The release rate of AtrCa from AtrCa- SMEDDS formulation (93.8%, at 15 minutes) was found as increased when the results were compared with commercial tablet formulation and pure drug. The permeability value of AtrCa from AtrCa- SMEDDS formulation was found higher than pure AtrCa and commercial tablet formulation, approximately 9.94 and 1.64 times, respectively. Conclusion: Thus, lipid-based SMEDDS formulation is a potential formulation candidate for lymphatic route in terms of the increased solubility of AtrCa.

Background: The domperidone maleate, a lipophilic agent classified as a Biopharmaceutical Classification System Class II substance with weak water solubility. Self- Emulsifying Drug Delivery System is a novel approach to improve water solubility and, ultimately bioavailability of drugs. Objective: This study aimed to develop and characterize new domperidone-loaded self-emulsifying drug delivery systems as an alternative formulation and to evaluate the permeability of domperidone-loaded self-emulsifying drug delivery systems by using Caco-2 cells and via single-pass intestinal perfusion method. Method: Three self-emulsifying drug delivery systems were prepared and characterized in terms of pH, viscosity, droplet size, zeta potential, polydispersity index, conductivity, etc. Each formulation underwent 10, 100, 200, and 500 times dilution in intestinal buffer pH 6.8 and stomach buffer pH 1.2, respectively. Female Sprague Dawley rats were employed for in situ single-pass intestinal perfusion investigations. Results: Results of the study revealed that the ideal self-emulsifying drug delivery systems formulation showed narrow droplet size, ideal zeta potential, and no conductivity. Additionally, as compared to the control groups, the optimum formulation had better apparent permeability (12.74 ± 0.02×10-4) from Caco-2 cell monolayer permeability experiments. The study also revealed greater Peff values (2.122 ± 0.892×10-4 cm/s) for the optimal formulation from in situ intestinal perfusion analyses in comparison to control groups (Domperidone; 0.802±0.418×10-4 cm/s). Conclusion: To conclude, prepared formulations can be a promising way of oral administration of Biopharmaceutical Classification System Class II drugs.