Table 1.
Formulation approaches designed to improve solubility and bioavailability of silymarin.
| Type of Formulation | Method of Preparation | Results | References |
|---|---|---|---|
| Nanocrystals, nanosuspensions | ESD | Rod-shaped NPs | Zhang et al. [42] |
| ESD | NPs < 200 nm | Liu et al. [43] | |
| HPH | NPs 637 and 132 nm | Whang et al. [44,46,53] | |
| HPH | Pickering emulsion | Yi et al. [54] | |
| Spray-drying | Dissolution studies | Hwang et al. [47] | |
| Spray-drying | Microparticles | Sansone et al. [50] | |
| Fluid-bed coating | Synchronized release | Wu et al. [48,49] | |
| Microfluidics | NP size 26–101 nm | Cui et al. [51] | |
| Antisolvent precip. | Dissolution studies | Sahibzada et al. [52] | |
| SEDS | Dissolution studies | Yang et al. [55] | |
| Inclusion complexes, phytosomes | Co-precipitation | Complex with β-CD | Ghosh et al. [57] |
| Freeze-drying | Complex with HP-CD | Kellici et al. [58] | |
| Kneading | HP-β-CD, RAMEB | Gharbia et al. [59] | |
| Solvent evaporation | Phospholipids | Yanyu et al. [61] | |
| Solvent evaporation | Phospholipids | Duan et al. [65] | |
| Mixed micelles | BS-phospholipids | Yu et al. [63] | |
| Mixed micelles | BS-phospholipids | Zhu et al. [64] | |
| Micro- and NanoEmulsions | Spontaneous emulsif. | Microemulsion | Panapisal et al. [66] |
| Low energy emulsif. | O/W emulsion | Abrol et al. [67] | |
| Low energy emulsif. | O/W emulsion | Parveen et al. [30] | |
| Low energy emulsif. | Nanoemulsion | Adhikari et al. [74] | |
| Low energy emulsif. | Nanoemulsion | Calligaris et al. [76] | |
| Low energy emulsif. | Nanoemulsion | Piazzini et al. [79] | |
| Membrane emulsif. | Nanoemulsion | Yang et al. [75] | |
| HPH | Nanoemulsion | Nagi et al. [77] | |
| SEDDS | Water titration | Wu et al. [70] | |
| SEDDS | Water titration | Woo et al. [71] | |
| SEDDS | Water titration | Li et al. [72] | |
| S-SEDDS | Supersaturated state | Wei et al. [73] | |
| Liposomes | Ethanol injection | Drug EE 95% | Maheshwari et al. [82] |
| RPE | Drug EE 69% | El-Samaligy et al. [83,84] | |
| TFD | Drug EE 55% | Kumar et al. [91] | |
| RPE | Phytosome | Angelico et al. [92,93] | |
| SEDS | Bile salt | Yang et al. [94] | |
| TFD | Bile salt | Mohsen et al. [95] | |
| PEGylated liposomes | TFD | Hepatic targeting | Elmowafy et al. [89] |
| PEGylated liposomes | TFD | Hepatic targeting | Ochi et al. [90] |
| Proliposomes | Film-deposition | Drug EE 93% | Xiao et al. [85] |
| Proliposomes | TFD-freeze drying | Drug EE 82% | Tong et al. [87,88] |
| Cubosomes | Melting/Congealing | Pluronic | Lian et al. [96] |
| Organogels | Mixed Solution | Lecithin/pluronic | Mady et al. [97] |
| Solid-Lipid Nanoparticles | TFD | Drug EE 99% | Xu et al. [102] |
| HPH | Lipolysis mechanism | Shangguan et al. [103] | |
| Cold/hot HPH | Drug EE 87% | He et al. [104] | |
| Hot HPH | NP size 165–200 nm | Cengiz et al. [105] | |
| Hot HPH | SIL-conjugates | Ma et al. [108,109] | |
| EES | Stealth SLNs | Zhang et al. [106] | |
| EES | Drug EE 92% | Piazzini et al. [107] | |
| Film hydration | SIL-emulsomes | Zhou et al. [110] | |
| Nanostructured Lipid Carriers | ESE | NP size 230 nm | Jia et al. [111,112] |
| ESE | NP size 126 nm | Iqbal et al. [115] | |
| ESE | NP size 225 nm | Chen et al. [116] | |
| Hot HPH | Drug EE 87% | Wu et al. [113] | |
| Emulsif./ultrasound | Drug EE 79% | Chaudhary et al. [114] | |
| Inclusion in polymeric matrices | Co-precipitation | Dissolution studies | Sonali et al. [118] |
| Complexation | Chitosan NPs | Nguyen et al. [119] | |
| ESE/freeze-drying | NP size 100 nm | Zhao et al. [120] | |
| Nanoprecipitation | Drug EE 79% | Gohulkumar et al. [121] | |
| Nanoprecipitation | Drug EE 89% | Younis et al. [122] | |
| Nanoprecipitation | Drug EE 83% | El-Nahas et al. [123] | |
| Solvent evaporation | Dissolution studies | Yousaf et al. [124] | |
| Dendrimers and polymeric NPs | PAMAM dendrimers | Solubility studies | Huang et al. [126] |
| PEG-PAMAM | Solubility studies | Diaz et al. [127] | |
| Polymeric micelles | Chitosan derivative | Sui et al. [128] | |
| ESE | PLGA | El-Sherbiny [129] | |
| ESE | PLGA | Snima et al. [130] | |
| ESE | PLGA | Xie et al. [131] | |
| ESE | PCL | Bonepally et al. [132] | |
| Ionic gelation | Chitosan-TPP | Pooja et al. [133] | |
| Nanoprecipitation | PE Sebacate NPs | Guhagarkar et al. [134] | |
| Ultrasonication | Polysaccharide NPs | Ma et al. [135] | |
| Ionic gelation | Chitosan/PGA | Lee et al. [136] | |
| Ionic gelation | Inulin NPs | Abdel-Wahhab et al. [137] | |
| Inorganic nanomaterials | Microemulsion | Mesoporous Si NPs | Cao et al. [139] |
| Ultrasonic corrosion | Porous Si NPs | Cao et al. [140,141] | |
| Drug conjugation | Carbon NT | Tan et al. [143] | |
| Precipitation | Calcium phosphate | Chen et al. [144] | |
| Precipitation | Calcium phosphate | Zhu et al. [145] | |
| Precipitation | PLGA-PEG-Fe3O4 | Ebrahimnezhad et al. [146] | |
| Coprecipitation | Chitosan-Fe3O4 | Khalkhali et al. [148] | |
| Emulsion-diffusion | PEG-PLGA-Au | Fazio et al. [149] |