Formulation of Gelucire®-Based Solid Dispersions of Atorvastatin Calcium: In Vitro Dissolution and In Vivo Bioavailability Study

Objective: The goal of the present investigation was to improve the solubility and bioavailability of atovaquone tablet, using in-house biosynthesized biosurfactant in the ternary system of solid dispersion containing hydrophilic polymers with varying concentrations of biosurfactant. Atovaquone is an anti-malarial agent and belongs to biopharmaceutical classification system class IV. Methods: The solid dispersion of binary and ternary mixture was prepared using hydroxyl propyl methyl cellulose (HPMC) and biosurfactant respectively by a solvent evaporation method. All the atovaquone tablet formulations were prepared by incorporation of physical mixture, binary and ternary solid dispersed products with excipients by direct compression method. Pre-compression and post-compression parameters of atovaquone tablets were evaluated. In vivo bioavailability study was performed using female albino rabbits. Results: In vitro dissolution profile of binary and ternary system of solid dispersion products showed 8.65% and 34.64% respectively. Precompression and post-compression values of all atovaquone tablets formulations were within the specified limits. In vitro dissolution efficiency of F2 and F5 were 1.44 fold and 6.62 fold respectively, in accordance to the F1. In vivo study revealed that bioavailability of optimized formulation F5 was increased by 2.5 times and time to reach peak concentration was reduced to 1.4 h, in accordance to pure atovaquone suspension. Conclusion: Potential application of biosurfactant in the solid dosage form of atovaquone tablet was proved for enhanced dissolution rate and bioavailability of atovaquone for malaria treatment.

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Preparation and Evaluation of Silymarin-Loaded Solid Eutectic for Enhanced Anti-Inflammatory, Hepatoprotective Effect: In Vitro–In Vivo Prospect

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/1818538 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Abdulla Sherikar ◽

Mohd Usman Mohd Siddique ◽

Mahesh More ◽

Sameer N. Goyal ◽

Milan Milivojevic ◽

...

Keyword(s):

Solid Dispersion ◽

Solid Dispersions ◽

Biological Response ◽

Eutectic Mixture ◽

Fold Increase ◽

In Vitro Dissolution ◽

Anti Inflammatory ◽

Pvp K30

Solubility of phytochemicals is a major concern for drug delivery, permeability, and their biological response. However, advancements in the novel formulation technologies have been helping to overcome these challenges. The applications of these newer technologies are easy for commercialization and high therapeutic outcomes compared to conventional formulations. Considering these facts, the present study is aimed to prepare a silymarin-loaded eutectic mixture with three different ratios of Polyvinylpyrrolidone K30 (PVP K30) and evaluating their anti-inflammatory, and hepatoprotective effects. The preliminary phytochemical and characterization of silymarin, physical mixture, and solid dispersions suggested and successfully confirmed the formation of solid dispersion of silymarin with PVP K30. It was found that the solubility of silymarin was increased by 5-fold compared to pure silymarin. Moreover, the in vitro dissolution displayed that 83% of silymarin released within 2 h with 2.8-fold increase in dissolution rate compared to pure silymarin. Also, the in vivo study suggested that the formulation significantly reduced the carbon tetrachloride- ( 0.8620 ± 0.05034 ∗ ∗ for 1 : 3 ratio), paracetamol- ( 0.7300 ± 0.01517 ∗ ∗ for 1 : 3 ratio), and ethanol- ( 0.8100 ± 0.04037 ∗ ∗ for 1 : 3 ratio) induced hepatotoxicity in rats. Silymarin solid dispersion was prepared using homogenization methods that have prominent anti-inflammatory effect ( 0.6520 ± 0.008602 ∗ ∗ with 8.33%) in carrageenan-induced rat paw model.

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Formulation, In Vitro and In Vivo Evaluation of Gefitinib Solid Dispersions Prepared Using Different Techniques

Processes ◽

10.3390/pr9071210 ◽

2021 ◽

Vol 9 (7) ◽

pp. 1210

Author(s):

Sultan Alshehri ◽

Abdullah Alanazi ◽

Ehab M. Elzayat ◽

Mohammad A. Altamimi ◽

Syed S. Imam ◽

...

Keyword(s):

Oral Absorption ◽

Solid Dispersions ◽

Water Soluble ◽

In Vitro Dissolution ◽

Pharmacokinetic Parameters ◽

Pharmacokinetic Studies ◽

In Vivo Evaluation ◽

Significant Release

Gefitinib (Gef) is a poorly water-soluble antitumor drug, which shows poor absorption/bioavailability after oral administration. Therefore, this study was carried out to develop Gef solid dispersions (SDs) using different carriers and different techniques in order to enhance its dissolution and oral absorption/bioavailability. Various SD formulations of Gef were established using fusion and microwave methods utilizing Soluplus, Kollidone VA64, and polyethylene glycol 4000 (PEG 4000) as the carriers. Developed SDs of Gef were characterized physicochemically and evaluated for in vitro dissolution and in vivo pharmacokinetic studies. The physicochemical evaluation revealed the formation of Gef SDs using fusion and microwave methods. In vitro dissolution studies indicated significant release of Gef from all SDs compared to the pure Gef. Optimized SD of Gef (S2-MW) presented significant release of Gef (82.10%) compared with pure Gef (21.23%). The optimized Gef SD (S2) was subjected to in vivo pharmacokinetic evaluation in comparison with pure Gef in rats. The results indicated significant enhancement in various pharmacokinetic parameters of Gef from an optimized SD S2 compared to the pure Gef. In addition, Gef-SD S2 resulted in remarkable improvement in bioavailability compared to the pure Gef. Overall, this study suggested that the prepared Gef-SD by microwave method showed marked enhancement in dissolution and bioavailability.

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Applying Supercritical Fluid Technology to Prepare Ibuprofen Solid Dispersions with Improved Oral Bioavailability

Pharmaceutics ◽

10.3390/pharmaceutics11020067 ◽

2019 ◽

Vol 11 (2) ◽

pp. 67 ◽

Cited By ~ 5

Author(s):

Fei Han ◽

Wei Zhang ◽

Ying Wang ◽

Ziyue Xi ◽

Lu Chen ◽

...

Keyword(s):

Binding Energy ◽

Supercritical Fluid ◽

Solid Dispersions ◽

Physical Stability ◽

In Vitro Dissolution ◽

Scanning Calorimetry ◽

Drug Concentrations ◽

Supercritical Fluid Technology

In this study, supercritical fluid (SCF) technology was applied to prepare reliable solid dispersions of pharmaceutical compounds with limited bioavailability using ibuprofen (IBU) as a model compound. Solid-state characterization of the dispersions was conducted by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The PXRD and DSC results suggested that the amorphous form of IBU was maintained in the solid dispersions. Furthermore, in vitro dissolution and in vivo pharmacokinetic (PK) studies in rats were also performed. The dissolution performance of the SCF-prepared IBU dispersions was significantly improved compared to that of the physical mixtures of crystalline IBU and a polymer. In addition, the PK results revealed that the SCF-prepared IBU dispersions produced remarkably high blood drug concentrations (both the AUC and Cmax) and a rapid absorption rate (Tmax). Finally, molecular modeling was used to evaluate the binding energy of interactions between IBU and the polymers. The negative binding energy suggests a relatively stable system. Hence, SCF technology can be used as a very effective approach to prepare IBU solid dispersions with good physical stability and enhanced in vitro and in vivo performance.

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Oral saquinavir mesylate solid dispersions: In vitro dissolution, Caco-2 cell model permeability and in vivo absorption studies

Powder Technology ◽

10.1016/j.powtec.2014.09.012 ◽

2015 ◽

Vol 269 ◽

pp. 200-206 ◽

Cited By ~ 3

Author(s):

Thiago Caon ◽

Jadel Muller Kratz ◽

Gislaine Kuminek ◽

Melina Heller ◽

Ricardo Augusto Konig ◽

...

Keyword(s):

Cell Model ◽

Solid Dispersions ◽

In Vitro Dissolution ◽

Absorption Studies ◽

In Vivo Absorption

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Effect of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of amorphous solid dispersions

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2017.04.007 ◽

2017 ◽

Vol 104 ◽

pp. 240-254 ◽

Cited By ~ 4

Author(s):

Weiwei Sun ◽

Baoliang Pan

Keyword(s):

Solid Dispersions ◽

Amorphous Solid ◽

In Vitro Dissolution ◽

Dissolution Behavior ◽

Amorphous Solid Dispersions ◽

Polymer Type

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On Absorption Modeling and Food Effect Prediction of Rivaroxaban, a BCS II Drug Orally Administered as an Immediate-Release Tablet

Pharmaceutics ◽

10.3390/pharmaceutics13020283 ◽

2021 ◽

Vol 13 (2) ◽

pp. 283

Author(s):

Varun Kushwah ◽

Sumit Arora ◽

Miklós Tamás Katona ◽

Dattatray Modhave ◽

Eleonore Fröhlich ◽

...

Keyword(s):

Pbpk Model ◽

Food Effect ◽

Solid Dispersions ◽

Immediate Release ◽

Oral Solution ◽

In Vitro Dissolution ◽

Fed State ◽

Release Tablet

The present work evaluates the food effect on the absorption of rivaroxaban (Riva), a BCS II drug, from the orally administered commercial immediate-release tablet (Xarelto IR) using physiologically based pharmacokinetic (PBPK) and conventional in vitro–in vivo correlation (IVIVC) models. The bioavailability of Riva upon oral administration of Xarelto IR tablet is reported to exhibit a positive food effect. The PBPK model for Riva was developed and verified using the previously reported in vivo data for oral solution (5 and 10 mg) and Xarelto IR tablet (5 and 10 mg dose strength). Once the PBPK model was established, the in vivo performance of the tablet formulation with the higher dose strength (Xarelto IR tablet 20 mg in fasted and fed state) was predicted using the experimentally obtained data of in vitro permeability, biorelevant solubility and in vitro dynamic dissolution data using United States Pharmacopeia (USP) IV flow-through cell apparatus. In addition, the mathematical IVIVC model was developed using the in vitro dissolution and in vivo profile of 20 mg strength Xarelto IR tablet in fasted condition. Using the developed IVIVC model, the pharmacokinetic (PK) profile of the Xarelto IR tablet in fed condition was predicted and compared with the PK parameters obtained via the PBPK model. A virtual in vivo PK study was designed using a single-dose, 3-treatment cross-over trial in 50 subjects to predict the PK profile of the Xarelto® IR tablet in the fed state. Overall, the results obtained from the IVIVC model were found to be comparable with those from the PBPK model. The outcome from both models pointed to the positive food effect on the in vivo profile of the Riva. The developed models thus can be effectively extended to establish bioequivalence for the marketed and novel complex formulations of Riva such as amorphous solid dispersions.

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