Formulation of a self-emulsifying system for oral delivery of simvastatin: In vitro and in vivo evaluation

Formulation of a self-emulsifying system for oral delivery of simvastatin: In vitro and in vivo evaluation The objective of the present work was to formulate a self-emulsifying drug delivery system (SEDDS) for simvastatin, which is widely used in the treatment of hypercholesterolemia and dyslipidemia as an adjunct to diet. Simvastatin SEDDS were formulated using a 1:1 (V/V) mixture of diesters of caprylic/capric acids and polyglycolyzed glycerides with varying concentrations of polyoxy castor oil and C8/C10 mono-/diglycerides. The developed SEDDS were evaluated for turbidimetry, droplet size analysis, drug content and in vitro diffusion profiles. In vivo performance of the optimized formulation was evaluated in rats using pharmacodynamic marker parameters like plasma total cholesterol (CH), triglycerides (TG) and high-density lipoprotein (HDL-CH) for 21 days. SEDDS containing 9.1% (m/m) simvastatin and 23.0% (m/m) of each excipient showed minimum mean droplet size (124 nm) and optimal drug diffusion. This test formulation showed significant reduction in plasma CH and TG (around 5-fold and 4-fold, respectively), while HDL-CH concentration was markedly higher (2-fold) compared a reference simvastatin suspension formulation after oral administration for 21 days of study. Test formulation has shown enhanced pharmacodynamic performance compared to reference formulation in rats. The study illustrated the potential of simvastatin SEDDS for oral administration and its biopharmaceutic performance.

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Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2020.13.5.7 ◽

2020 ◽

Vol 13 (5) ◽

pp. 5102-5109

Author(s):

Venu Madhav K ◽

Somnath De ◽

Chandra Shekar Bonagiri ◽

Sridhar Babu Gummadi

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Solid Dispersions ◽

In Vitro Release ◽

Aqueous Solubility ◽

Water Soluble ◽

Scanning Calorimetry ◽

In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension. From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

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Design and evaluation of a novel floating osmotic pump system

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j33k5n ◽

2009 ◽

Vol 12 (1) ◽

pp. 129 ◽

Cited By ~ 3

Author(s):

Zhihong Zhang ◽

Bo Peng ◽

Xinggang Yang ◽

Chao Wang ◽

Guangmei Sun ◽

...

Keyword(s):

Drug Release ◽

Oral Administration ◽

In Vitro Release ◽

Osmotic Pump ◽

Matrix Tablets ◽

In Vivo Evaluation ◽

Pump System ◽

Conventional Tablet

PURPOSE. Find a novel delivery system for oral administration of drugs that have absorption window in the upper part of gastrointestinal (GI) track. METHODS. Dipyridamole was chosen as the model drug. A novel system, which combined the osmotic pump controlled release system and the floating system, was designed; matrix tablets (MT) were prepared for compares. The effects of pH, temperature and hydrodynamic conditions on drug release and the floating behavior of floating osmotic pump system (FOP) were investigated. In vivo evaluation was performed by a three-crossover study in six Beagle dogs relative to the conventional tablet (CT). Cumulative percent input in vivo was compared with that of in vitro release profiles. RESULTS. Floating behavior of FOP, drug releases from FOP and MT were sensitive to pH of dissolution media but not sensitive to temperature; the release of dipyridamole from MT was influenced by stirring rate while drug release from FOP was not. AUC of FOP was larger than MT and CT. The linear correlations between fraction absorbed in vivo and fraction dissolved in vitro was established for FOP-a true zero-order release formula, whereas only a nonlinear correlation was obtained for MT. CONCLUTIONS. FOP could be a novel way for the oral administration for drugs like dipyridamole.

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Preparation and in vitro and in vivo evaluation of quercetin-loaded mixed micelles for oral delivery

Bioscience Biotechnology and Biochemistry ◽

10.1080/09168451.2017.1419852 ◽

2018 ◽

Vol 82 (2) ◽

pp. 238-246 ◽

Cited By ~ 3

Author(s):

Zhen Lu ◽

Cuiping Bu ◽

Weicheng Hu ◽

Hui Zhang ◽

Mengrui Liu ◽

...

Keyword(s):

Oral Delivery ◽

Mixed Micelles ◽

In Vivo Evaluation

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DEVELOPMENT AND OPTIMIZATION OF ZALEPLON LOADED EUDRAGIT® NANOPARTICLES FOR ORAL DELIVERY: IN-VITRO AND IN-VIVO EVALUATION

International Research Journal of Pharmacy ◽

10.7897/2230-8407.1007236 ◽

2019 ◽

Vol 10 (7) ◽

pp. 154-162

Author(s):

Sanaa A El-Gizawy ◽

Ebtessam A Essa ◽

Ahmed Kh Abosalha

Keyword(s):

Oral Delivery ◽

In Vivo Evaluation

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In Vitro, Ex Vivo and In Vivo Evaluation of Microcontainers for Oral Delivery of Insulin

Pharmaceutics ◽

10.3390/pharmaceutics12010048 ◽

2020 ◽

Vol 12 (1) ◽

pp. 48 ◽

Cited By ~ 1

Author(s):

Jacob Rune Jørgensen ◽

Feiyang Yu ◽

Ramakrishnan Venkatasubramanian ◽

Line Hagner Nielsen ◽

Hanne Mørck Nielsen ◽

...

Keyword(s):

Oral Delivery ◽

Ex Vivo ◽

Sodium Dodecyl ◽

Insulin Absorption ◽

Oral Gavage ◽

In Vivo Evaluation ◽

Sodium Caprate ◽

Intestinal Membrane

Enhancing the oral bioavailability of peptides has received a lot of attention for decades but remains challenging, partly due to low intestinal membrane permeability. Combining a permeation enhancer (PE) with unidirectionally releasing microcontainers (MCs) has previously been shown to increase insulin permeation across Caco-2 cell monolayers. In the present work, this setup was further employed to compare three common PEs—sodium caprate (C10), sodium dodecyl sulfate (SDS), and lauroyl carnitine. The concept was also studied using porcine intestinal tissue with the inclusion of 70 kDa fluorescein isothiocyanate-dextran (FD70) as a pathogen marker. Moreover, a combined proteolysis and Caco-2 cell permeation setup was developed to investigate the effect of soybean trypsin inhibitor (STI) in the MCs. Lastly, in vivo performance of the MCs was tested in an oral gavage study in rats by monitoring blood glucose and insulin absorption. SDS proved to be the most potent PE without increasing the ex vivo uptake of FD70, while the implementation of STI further improved insulin permeation in the combined proteolysis Caco-2 cell setup. However, no insulin absorption in rats was observed upon oral gavage of MCs loaded with insulin, PE and STI. Post-mortem microscopic examination of their gastrointestinal tract indicated lack of intestinal retention and optimal orientation by the MCs, possibly precluding the potential advantage of unidirectional release.

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