Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation

Abstract

The main purpose of this study was to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Olmesartan (OLM) for enhancement of its solubility and dissolution rate. In this study, liquid SNEDDS containing Olmesartan was formulated and further developed into a solid form by the spray drying technique using Aerosil 200 as a solid carrier. Based on the preliminary screening of different unloaded SNEDDS formulae, eight formulae of OLM loaded SNEEDS were prepared using Capryol 90, Cremophor RH40 and Transcutol HP as oil, surfactant and cosurfactant, respectively. Results showed that the mean droplet size of all reconstituted SNEDDS was found to be in the nanometric range (14.91–22.97 nm) with optimum PDI values (0.036–0.241). All formulae also showed rapid emulsification time (15.46 ± 1.34–24.17 ± 1.47 s), good optical clarity (98.33% ± 0.16%–99.87% ± 0.31%) and high drug loading efficiency (96.41% ± 1.20%–99.65% ± 1.11%). TEM analysis revealed the formation of spherical and homogeneous droplets with a size smaller than 50 nm. In vitro release of OLM from SNEDDS formulae showed that more than 90% of OLM released in approximately 90 min. Optimized SNEDDS formulae were selected to be developed into S-SNEDDS using the spray drying technique. The prepared S-SNEDDS formulae were evaluated for flow properties, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), reconstitution properties, drug content and in vitro dissolution study. It was found that S-SNEDDS formulae showed good flow properties and high drug content. Reconstitution properties of S-SNEDDS showed spontaneous self-nanoemulsification and no sign of phase separation. DSC thermograms revealed that OLM was in solubilized form and FTIR supported these findings. SEM photographs showed smooth uniform surface of S-SNEDDS with less aggregation. Results of the in vitro drug release showed that there was great enhancement in the dissolution rate of OLM. To clarify the possible improvement in pharmacokinetic behavior of OLM S-SNEDDS, plasma concentration-time curve profiles of OLM after the oral administration of optimized S-SNEDDS formula (F3) were compared to marketed product and pure drug in suspension. At all time points, it was observed that OLM plasma concentrations in rats treated with S-SNEDDS were significantly higher than those treated with the drug in suspension and marketed product.

<p>Proniosomal Telmisartan Tablets: Formulation, in vitro Evaluation and in vivo Comparative Pharmacokinetic Study in Rabbits</p>

“…The results were in perfect agreement with the previous researchers who prepared stable colloidal system with a low negative zeta potential system. 27,28 The absolute values of zeta potential were lower than the literature which may be attributed to the presence of non-ionic surfactant which sterically stabilizes the system by forming a coat around their surface. For personal use only.…”

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“…A drop of the diluted emulsion was placed on a film coated 400-mesh copper grids for 30 min and excess fluid was removed with the help of filter paper. The samples were later stained with 2% (w/v) phosphotungstic acid for 30 seconds and then dried for 20 min before observation 16 .…”

Effect of Oily Ingredients and Solid Adsorbents on the Chemical Stability of a Solid Dosage Form of Lubiprostone

“…Solid carriers such as colloidal silica (Aerosil®, Evonikindustries, Essen, Germany), calcium silicate (Florite™, Tomita Pharmaceutical Co., Ltd, Tokushima, Japan), microcrystalline cellulose (MCC) and magnesium aluminum silicate (Neusilin®, Fuji Chemical Industries Co., Ltd, Toyama, Japan) provide high surface area with good disintegration characteristics. The porous carriers retaining oily ingredients can be supplementary, filled into hard capsules, or blended with compressible excipients for tabletization, providing improved patient compliance, and a more economical manufacturing process than soft gelatin capsules …”

“…The porous carriers retaining oily ingredients can be supplementary, filled into hard capsules, or blended with compressible excipients for tabletization, providing improved patient compliance, and a more economical manufacturing process than soft gelatin capsules. 12 In preparing a solid dosage form of oily ingredients and/or compositions, case-specific formulation studies are prerequisite, as the aforementioned pharmaceutical approaches are largely dependent on the physicochemical property of the pharmaceutically active ingredient, and its compatibility with oily ingredients and/or porous adsorbents. To the best of our knowledge, investigations on the solidification of LPT-loaded oily vehicle are yet to be reported.…”