Int J App Pharm, Vol 14, Issue 6, 2022, 1-8Review Article



1Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, West Java, Indonesia

Received: 13 Jul 2022, Revised and Accepted: 24 Sep 2022


Natural ingredients have been a source of medicine since ancient times. Research on the development of natural ingredients as medicinal ingredients has increased. One of these is isolating active substances from herbs in a pure state (isolate). However, some problems hinder the use of isolates as the primary treatment option, one of which is solubility. Most isolates had poor solubility, inhibiting the body's absorption process. This review investigates the method and polymer to increase the solubility of isolates and summarizes the development of drugs from isolates. This review also explains how effectively the method and polymer improve the solubility or dissolution of the isolate. We expect the results to be a reference for research on isolates with poor solubility.

Keywords: Solubility, Isolate, Solubility enhancement method, Polymer


Natural ingredients have been used as a source of medicine since ancient times. They were using natural materials that coincided with the beginning of human life on earth. Humans needed natural materials as staple food and as medicine. Using drugs from natural ingredients based on empirical results is carried out from generation to generation. It is recorded as far back as 5000 BC in Sumerian, Egyptian, Greek, and Roman cultures [1]. Drugs from natural ingredients are usually still in an impure form containing several constituents believed to have a synergistic effect on producing the desired therapy [2]. Currently, medicinal preparations from natural ingredients continue to be developed and researched to overcome various diseases. However, there are problems with the use of natural materials. One is poor solubility, especially in water, due to using nonpolar or semi-polar solvents during the extraction process to isolation [3].

Table 1: Solubility classification based on farmakope Indonesia VI [4]

Solubility definition Part of solvent required for one part of solute (g/ml)
Very soluble <1
Freely soluble From 1 to 10
Soluble From 10 to 30
Sparingly soluble From 30 to 100
Slightly soluble From 100 to 1000
Very slightly soluble From 1000 to 10.000
Practically insoluble >10.000

Solubility is the maximum amount of a substance that can be dissolved in a certain amount of solvent at a given temperature [5]. Quantitatively defined as a solute concentration in a saturated solution at a specific temperature [6]. Solubility depends on the characteristics of the solvent, temperature, and pressure. The solvent can be a single liquid or a combination of liquids, where the characteristics of the solvent will affect the solute, polar solvents will dissolve polar substances, and nonpolar solvents will dissolve nonpolar substances [5]. Polar substances easily dissolve in water but have poor membrane permeability [7]. The pH level of the solvent affects the solubility of substances, acidic substances will be more soluble in alkaline solvents, and alkaline substances will more easily dissolve in acidic solvents; the ionization process influences this. Particle size affects the solubility of a substance; the smaller the particle size, the easier the substance is dissolved in the solvent because of the more significant the surface area of ​​the substance. The form of a substance also affects solubility; crystalline forms will be more difficult to dissolve than amorphous ones [5].

Solubility is one of the main parameters in the rate of absorption, dissolution, and bioavailability. Drug absorption through the oral and parenteral routes will be affected by its solubility in water [8]. Dissolution is an in vitro drug release test required to simulate the release rate of solid or semisolid drugs into a liquid solvent under standardized temperature, stirring, velocity, volume, and media composition [9]. Meanwhile, bioavailability is the rate and amount of the active drug substance absorbed and available at the drug's site of action. The drug absorbed rate and the amount is usually measured by AUC and Cmax (maximum concentration) [10]. The results of in vivo bioavailability testing will be influenced by the solubility of the drug in water [8].

Table 2: Isolate solubility data

Isolate Solubility in water Solubility class Reference
Curcumin 1.34±0.02 mg/l Practically insoluble [11]
Piperine 2.93 µg/ml Practically insoluble [12]
Quercetin 0.21±0.14 µg/ml Practically insoluble [13]
Andrographolide 0.10 mg/ml Very slightly soluble [14]
Rutin 0.045±0.002 mg/ml Practically insoluble [15]
Myricetin 16.60±0.92 µg/ml Practically insoluble [16]
Daidzein 3.84±0.13 µg/ml Practically insoluble [17]
Naringenin 43.83±0.039 µg/ml Practically insoluble [18]
Luteolin 2.5 µg/ml Practically insoluble [19]

Table 3: Isolate dissolution data

Isolate Dissolution Reference
Curcumin Intrinsic: 7.96 x 10-3 mg/cm2. minute in 40% Ethanol [20]
Piperine 45.30% at minute 60 in water [12]
Quercetin 1.1% at minute 60 in phosphate buffer [21]
Andrographolide 20% at minute 60 in water [22]
Rutin 22% at minute 120 in SLS 0.1% pH 1.2 [15]
Myricetin Intrinsic: 9.89 µg/cm2. minute in water [23]
Daidzein 5.30% at minute 45 in water [24]
Naringenin 22% at minute 120 in water [25]
Luteolin 13.11% at minute 90 in 0.1 N HCl [26]

Different processes or modifications of the isolate were carried out to increase the solubility. Solid dispersion, inclusion complex, micelles, cocrystals, and nanosuspensions are various methods to increase solubility. This review will describe the methods that can increase the solubility of isolates. The increase in solubility can be assessed from the isolate's solubility, dissolution, and bioavailability tests.


The writing of this article began in February 2021 through journal searches on Google Scholar and Pubmed using the keywords "Improvement of isolate solubility" or "Solubility Enhancement of Isolate." The inclusion criteria of this journal are the results of research that developed a method of increasing the solubility of isolates with solubility or dissolution testing published in 2013-2022. Exclusion criteria are journals that are the result of a review with a related theme and which cannot be accessed entirely.


Solubility enhancement method

Fig. 1: Solubility enhancement method in isolate (designed by authors)


In recent years, nanoparticles have been widely used in pharmaceuticals, significantly increasing drug solubility [27]. Nanoparticles are defined as particles having a size of 1-100 nm, of which 50% of the particle distribution should be in this range [28]. Nanoparticles can be a solution to overcoming problems in drugs derived from herbal plants [29]. Reducing the particle size will increase the solubility of the particles because it increases the surface area and reduces the thickness of the protective layer of the particles [30]. It is proven by testing the dissolution of drugs belonging to the BCS class II class, namely hydrochlorothiazide, aceclofenac, and ibuprofen, with a size of<150 nm, with more drugs dissolved in the dissolution medium than the larger size [31].

Nanoparticles consist of several types distinguished from the material of manufacture and the system. Liposomes are the first generation of nanosized drug delivery systems [32]. Liposomes are nanosystems formed from a hydrophilic core surrounded by one or more phospholipid bilayers [33]. This phospholipid bilayer is usually biodegradable and biocompatible lipids, such as glycerophospholipids and phosphatidylcholine. Liposomes have become valuable medication delivery devices because they can encapsulate hydrophilic or lipophilic active compounds [34]. An example of the use of liposomes in isolates is curcumin, where curcumin is insoluble in water [35]. Curcumin is the main constituent of the Curcuma longa plant, commonly called turmeric [36]. Liposomes of curcumin were prepared using the thin film hydration method, in which curcumin (200 mg), cholesterol (500 mg), and soybean lecithin (500 mg) were dissolved in a mixed solvent of methanol: chloroform (1:9) which was shaken to form a thin layer of oil. The results of the curcumin liposome test showed that the drug release in phosphate buffer pH 7.4 (with dialysis membrane) reached 70.96% [37].

Fig. 2: Liposome (designed by authors)

Solid Lipid Nanoparticle (SLN) is a nano-delivery system that is an alternative to liposomes. SLN consists of 0.1-30% solid fat dispersed in the aqueous phase, to which 0.5-5% surfactant is added as a stabilizer [38]. The fats used are divided based on their structure: fatty acids, esters, fatty alcohols, and triglycerides [39]. An example of using SLN in isolates is piperine, where piperine is insoluble in water [40]. Piperine is a biological component isolated from the Piper nigrum plant [41]. SLN piperine was prepared by emulsification-solvent diffusion method, where piperine, glycerol monostearate, and epikuron 200 were mixed in demineralized water, then emulsified with benzyl alcohol (containing tween 80). The results of the piperine release test in the brains of the test animals showed that the piperine SLN had Cmax: 121±6.78 ng/g and Tmax: 60±9.8 min, while the results of pure piperine were Cmax: 51±9.34 ng/g and Tmax: 180±10.3. The increase in Cmax is doubled, and Tmax is achieved much faster [42].

Nanomicelles are nanosystems consisting of amphiphilic colloidal structures measuring 5-100 nm. There are two parts of this micelle based on their affinity in water: a hydrophilic and a hydrophobic part [43]. Nanomicell will work as a protective shell of the drug from the body's environment, thereby increasing the bioavailability of the drug and reducing side effects [44]. An example of nano micelles is in water-insoluble quercetin [45]. Quercetin is abundant in broccoli, oranges, apples, green tea, and onions [46]. The preparation of quercetin nano micelles used the thin-film hydration method, in which quercetin with polymer (10 mmol) was dissolved in ethanol and evaporated with a rotary evaporator under low pressure. The test results showed an increase in the solubility of quercetin in the form of nano micelles, which increased up to three times compared to pure quercetin [47].

PLGA (Poly lactic-co-glycolic acid) is the most commonly used polymer in developing nanoparticles because it can be degraded in the body. PLGA will be hydrolyzed into lactic acid and glycolic acid, which are metabolized through the Krebs cycle to carbon dioxide and water [48]. The FDA has approved PLGA for use in the human nanomedicine field [49]. An example of using PLGA nanoparticles is in quercetin, where PLGA-quercetin nanoparticles are made using the solvent evaporation method. The test results showed that the release profile of quercetin bound to PLGA nanoparticles reached 65%, while pure quercetin did not reach 40% [50].

Solid dispersion

A solid dispersion is a mixture of solid materials consisting of at least two different components with different properties, which are hydrophilic and hydrophobic [51]. The solid dispersion is applied to a substance having poor solubility, and then the substance is dispersed in a solid polymer [52, 53]. Solid dispersion is one method widely used to increase the solubility of a substance [54].

An example of solid dispersions is in curcumin, which is made using soluplus polymer and solvent evaporation preparation. Firstly, curcumin and soluplus were dissolved in acetone. Then acetone was evaporated. This solid dispersion of curcumin has a dissolution efficiency of 94.84±2.54%, while pure curcumin does not reach 60% [55]. In addition to soluplus, eudragit EPO polymer can be used to form solid dispersions with curcumin. Make this solid dispersion using a spray dryer with acetone solvent. The dissolution results showed that the release of curcumin in solid dispersion outperformed the release rate of pure curcumin, where the release of solid dispersion reached 40% at pH 6.8 while pure curcumin was below 20% [56]. PEG and HPMCAS polymers have also been shown to increase the release and solubility of curcumin [57, 58].

Fig. 3: Ideal solid dispersion (designed by authors)

Another example is the formation of solid dispersions of piperine using PEG, sorbitol, and PVP. Solid dispersion preparation by solvent evaporation method where piperine is dissolved in ethanol. The release of pure piperine in the 2nd hour of the dissolution test was 4.4%, while the release in the form of solid dispersion reached 70% (Sorbitol), 76% (PEG), and 89% (PVP) [59]. In other isolates, such as quercetin and andrographolide, solid dispersion was able to increase the release in the dissolution test [60-62]. Then in myricetin, solid dispersion increases solubility in water [63].


The complex is an intermolecular combination of substrate and ligand due to covalent or non-covalent bonds (hydrogen bonds, van der Waals forces, electrostatic bonds, and dipole-dipole forces). The most frequently used complexing agent is cyclodextrin [64]. Complexation can increase the solubility of substances in water and the speed of dissolution. There are several types of complexes, namely coordination complexes (metal complexes), molecular complexes, and inclusion complexes [65].

A coordination/metal complex consists of a central metal ion/atom bonded to a ligand. If derived from natural materials, usually, these metals bind to ligands involved in photosynthesis or metabolism [66]. Some metals that can form complexes are Fe2+, Fe3+, Co2+, Co3+, Cu2+, Zn2+, Ag+, and Pt4+, which are transition metal ions. Covalent bonds bind the metal to the ligand (neutral or anionic) [64]. Examples of the application of coordination complexes are curcumin and quercetin, which bind to magnesium (Mg) and calcium (Ca). In this complex, each metal molecule contains two molecules of curcumin or quercetin. The solubility of curcumin and quercetin in the complex form increases, whereas in the pure state, the solubility in water is 0.15 mg/l (curcumin) and 0.21 mg/l (quercetin) to 1.442 mg/ml (Mg-curcumin), 1.508 mg/l. ml (Ca-curcumin), 1.696 (Mg-quercetin), and 1.808 mg/ml (Ca-quercetin) [67].

Molecular complexes consist of substrates and ligands bound by non-covalent bonds that tend to be weak [64]. Examples of non-covalent bonds that bind substrates and ligands are hydrogen bonds, electrostatic forces, van der Waals forces, and hydrophobic forces [65]. An example of molecular complexes is apigenin, where apigenin is bound to phospholipids by hydrogen bonds. These apigenin and phospholipid complexes are more commonly referred to as pyrosomes, increasing their water solubility up to 35 times compared to pure apigenin. The solubility of phytosomes in water was 22.80±1.40 g/ml, while pure apigenin was only 0.62±0.88 g/ml due to a decrease in the crystalline level of apigenin which turns into a partially amorphous form [68].

Fig. 4: Inclusion complex (designed by authors)

The inclusion complex consists of two or more molecules, one acting as a "host" and the other as a "guest". Hydrophobic molecules will stick to the gaps of molecules that act as hosts and are hydrophilic [69]. An example of the use of inclusion complexes is in naringenin. Naringenin belongs to the flavonoid group found in oranges or tomatoes. Naringenin is insoluble in water and soluble in alcohol [70]. The formation of the naringenin inclusion complex with cyclodextrin increased its solubility in water, where the solubility of pure naringenin was 41.81 g/ml, while in the form of the inclusion complex, it was 74.28 g/ml. The increase in solubility was due to the inclusion complex structure protecting the hydrophobic moiety of naringenin [71].

A further example is piperine made into inclusion complexes with HPMC and-cyclodextrin increasing release in the dissolution test. The results showed that the piperine release in 60 min reached 95.78%, while pure piperine was only 22.04% [72]. Using ethylenediamine cyclodextrin in piperine also increased the dissolution release, where the release of pure piperine in the 5th minute was 35%, and the 60th min was 40%, while the inclusion complex in the 5th minute had reached 70% and at the-60 reaches 100% [73]. In other isolates, namely curcumin, quercetin and myricetin, the formation of inclusion complexes with cyclodextrin also increased the release in the dissolution test [74-76].


Microencapsulation by spray drying is an encapsulation technology that has been widely used and allows the active component to enter into a sturdy, spherical, semipermeable polymer matrix called microcapsules [77]. Microencapsulation consists of tiny particles or droplets surrounded by a film or polymer layer to protect them from the environment and regulate their release [78]. Microencapsulation is also used to mask bitter tastes, increase solubility [79], and prevent drug degradation [80]. In addition, using micro-encapsulation can increase its bioavailability during oral administration. The maximum concentration of encapsulated curcumin in eudragit was 478.45 ng/ml in blood plasma, while pure curcumin was only 89.67 ng/ml [81].

Fig. 5: Microencapsulation (designed by authors)

Solubility enhancement polymer


Cyclodextrins (SD) are synthesized from starch by enzymatic reactions into cyclic oligosaccharides. Cyclodextrins are non-toxic, biodegradable and natural [82]. Cyclodextrins consist of some glucopyranose monomers attached to 1,4-glycoside bonds [83]. Unmodified cyclodextrins have poor solubility and cannot bind strongly to drug molecules. Meanwhile, cyclodextrin derivatives have good solubility, are stable, and can bind to drug molecules [82]. Some examples of cyclodextrin derivatives are-SD,-SD,-SD, Hydroxypropyl-α-SD (HP-α-SD), Hydroxypropyl-β-SD (HP-ß-SD), Hydroxypropyl-γ-SD (HP-γ-SD), Sulphobutylether-SD, 2-Hydroxypropyl-γ-SD, ethylenediamine cyclodextrin (E-ß-SD), and methylated-β-SD [84]. Cyclodextrins were used to increase the solubility of curcumin solid dispersions [85] and curcumin inclusion complexes [86-87].

Table 4: Cyclodextrin use in isolate

Type Isolate Method Reference
HP-ß-SD Curcumin Solid Dispersion [85]
Inclusion Complex [86-88]
Myricetin Inclusion Complex [76]
ß-SD Piperine Inclusion Complex [72]
Naringenin Inclusion Complex [71]
Quercetin Inclusion Complex [75]
E-ß-SD Piperine Inclusion Complex [73]
HP-α-SD Curcumin Inclusion Complex [88]
HP-γ-SD Curcumin Inclusion Complex [88]


Polyvinylpyrrolidone (PVP) is a polymer consisting of a linear group of 1-vinyl-2-pyrrolidone. This polymer has a carbon chain containing an amide group on the side chain and a poly-N-vinyl amide structure. PVP is non-toxic, biocompatible, inert, and stable [89]. PVP has good solubility in water and solvents with polar properties [90]. PVP can envelop hydrophilic and lipophilic drugs, making them suitable for use in the modification of drug delivery [91]. PVP increases solubility through solid dispersion systems in quercetin, curcumin, and rutin [35].

Table 5: PVP use in isolate

Type Isolate Method Reference
PVP-K30 Curcumin Solid Dispersion [35]
Quercetin Solid Dispersion [35]
Rutin Solid Dispersion [35]
Piperine Solid Dispersion [59]
PVP Myricetin Solid Dispersion [92]
Daidzein Solid Dispersion [93]

Hydroxy propyl methyl cellulose

Hydroxy Propyl Methyl Cellulose (HPMC) is cellulose obtained by treating alkaline cellulose with chloromethane and propylene oxide. HPMC is a powder soluble in cold water, odourless, tasteless, and white [94]. HPMC can be stable in the pH range of 3–11 and can form solid dispersions to stabilize amorphous substances. According to the FDA and EMA, HPMC has also been classified as a safe excipient [95]. HPMC was used to increase the solubility of the piperine inclusion complex [72] and the solid dispersion of quercetin [62].

Table 6: HPMC use in isolate

Type Isolate Method Reference
HPMC Piperine Inclusion Complex [72]
Quercetin Solid Dispersion [62]
Myricetin Solid Dispersion [92]
Curcumine Solid Dispersion [96]

Polyethylene glycol

Polyethylene glycol (PEG) is a hydrophilic polymer synthesized from ethylene oxide. This polymer consists of repeating O-CH2-CH2 units [97] and has good solubility in water, ethanol, acetonitrile, benzene, and dichloromethane. PEG has many forms, such as forked, star, and comb. PEG can bind to drug molecules, which will prevent drug molecules from binding to proteins. PEG binding to drug molecules is called PEGylation [98]. PEG increased the solubility of luteolin solid dispersions [26] and quercetin solid dispersions [99].

Table 7: PEG use in isolate

Type Isolate Method Reference
PEG 4000 Luteolin Solid Dispersion [26]
Curcumin Solid Dispersion [58]
PEG 6000 Curcumin Solid Dispersion [58]
PEG 8000 Quercetin Solid Dispersion [99]
PEG 20000 Piperine Solid Dispersion [59]


Chitosan is a random copolymer resulting from chitin deacetylation, formed from D-glucosamine and N-acetyl-D-glucosamine linked to-1,4 glycosidic [100]. Chitosan is a natural cationic polysaccharide and is non-toxic [101]. The solubility of chitosan depends on molecular weight, degree of acetylation, pH, temperature, and crystallinity [102]. There is also chitosan which is modified by adding a hydrophilic group so that it has good solubility in water. Synthesis of water-soluble chitosan can be done by breaking the polymer chain through an enzymatic hydrolysis process to reduce the molecular weight of chitosan and increase the solubility of chitosan. In addition, there is a graft polymerization method in which chitosan polymer is added with a water-soluble dicyandiamide branch [103]. Chitosan was used to increase the curcumin nano complexes' release rate [104].


Eudragit is a polymer that has many types with different solubility properties. Eudragit is a synthetic polymethacrylates polymer with anionic, cationic, and nonionic properties consisting of a combination of dimethylaminoethyl methacrylates, methacrylic acid, and methacrylic acid esters with different ratios. Eudragit is stable, has good compressibility, and regulates drug release based on environmental pH [105]. Eudragit was used to increase the solubility of curcumin in solid dispersion [56] and microencapsulation [81].


Poly(lactic-co-glycolic acid), abbreviated as PLGA, is a synthetic polymer that can be degraded naturally, biocompatible, and non-toxic. PLGA was synthesized from lactide and glycolide, combined at a temperature of 160–190oC under vacuum with a stannous octoate catalyst. These polymers have characteristics that depend on the percentage of lactide and glycolide, such as crystal shape, density, and glass transition temperature [106]. PLGA was used in the formation of quercetin nanoparticles in order to increase their dissolution [107].


Soluplus is another name for the polymer polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer, which is an amphiphilic polymer with excellent solubility, so it is used in increasing the solubility of drugs. Good solubility because soluplus has many hydroxyl groups [108]. Soluplus increased the solubility of curcumin solid dispersions [55].


Based on this literature review, it can be concluded that the solubility problem of isolates can be overcome by applying the isolate modification method and combining isolates with polymers. Further research is needed to assess the effectiveness of these methods and polymers in increasing the solubility of isolates.


The author is grateful to his supervisor, Mr Dr. apt. Sriwidodo, M. Si and Mrs. Prof. Dr. rer. nat. apt. Anis Yohana Chaerunisaa, M. Sc. helped and motivated the author to write this article.


FDRN: conception, design, and drafting of the article. S and AYC: participated in intellectual discussions and critical revision of the article. All authors approved the final version of the manuscript.


The authors declare that there are no conflicts of interest in this article.


  1. Santic Z, Pravdic N, Bevanda M, Galic K. The historical use of medicinal plants in traditional and scientific medicine. Psychiatr Danub. 2017;Suppl 4:787-92. PMID 29278625.

  2. Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol. 2014;4:177. doi: 10.3389/fphar.2013.00177. PMID 24454289.

  3. Zhao J, Yang J, Xie Y. Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: an overview. Int J Pharm. 2019;570(Aug):118642. doi: 10.1016/j.ijpharm.2019.118642. PMID 31446024.

  4. Kemenkes RI. Farmakope Indonesia VI. Jakarta: Departemen Kesehatan Republik Indonesia; 2020.

  5. Singh N, Singh AP, Singh AP. Solubility: an overview. Int J Pharm Chem Anal. 2021;7(4):166-71. doi: 10.18231/j.ijpca.2020.027.

  6. More SD, Sontakke SB. Solubility enhancement of gliclazide by solid dispersion method. Asian J Pharm Clin Res. 2013;6Suppl 5:91-8.

  7. Coltescu AR, Butnariu M, Sarac I. The importance of solubility for new drug molecules. Biomed Pharmacol J. 2020;13(2):577-83. doi: 10.13005/bpj/1920.

  8. Khadka P, Ro J, Kim H, Kim I, Kim JT, Kim H. Pharmaceutical particle technologies: an approach to improve drug solubility, dissolution and bioavailability. Asian J Pharm Sci. 2014;9(6):304-16. doi: 10.1016/j.ajps.2014.05.005.

  9. Gray VA, Rosanske TW. Dissolution. Specif drug subst. Prod. 2020:481-503.

  10. Chung Chow S. Bioavailability and bioequivalence in. Drug Dev. 2014;6(4):304-12.

  11. Carvalho DdM, Takeuchi KP, Geraldine RM, Moura CJd, Torres MCL. Production, solubility and antioxidant activity of curcumin nanosuspension. Food Sci Technol (Campinas). 2015;35(1):115-9. doi: 10.1590/1678-457X.6515.

  12. Zaini E, Afriyani, Fitriani L, Ismed F, Horikawa A, Uekusa H. Improved solubility and dissolution rates in novel multicomponent crystals of piperine with succinic acid. Sci Pharm. 2020;88(2):1-13. doi: 10.3390/scipharm88020021.

  13. Lu B, Huang Y, Chen Z, Ye J, Xu H, Chen W. Niosomal nanocarriers for enhanced skin delivery of quercetin with functions of anti-tyrosinase and antioxidant. Molecules. 2019;24(12). doi: 10.3390/molecules24122322, PMID 31238562.

  14. Yen CC, Chen YC, Wu MT, Wang CC, Wu YT. Nanoemulsion as a strategy for improving the oral bioavailability and anti-inflammatory activity of andrographolide. Int J Nanomedicine. 2018;13:669-80. doi: 10.2147/IJN.S154824, PMID 29440893.

  15. Abdelkader H, Fathalla Z. Investigation into the emerging role of the basic amino acid L-lysine in enhancing solubility and permeability of BCS Class II and BCS Class IV drugs. Pharm Res. 2018;35(8):160. doi: 10.1007/s11095-018-2443-0, PMID 29916057.

  16. Yao Y, Lin G, Xie Y, Ma P, Li G, Meng Q. Preformulation studies of myricetin: A natural antioxidant flavonoid. Pharmazie. 2014;69(1):19-26. PMID 24601218.

  17. Ma Y, Zhao X, Li J, Shen Q. The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability. Int J Nanomedicine. 2012;7:559-70. doi: 10.2147/IJN.S27641, PMID 22346351.

  18. Semalty A, Semalty M, Singh D, Rawat MSM. Preparation and characterization of phospholipid complexes of naringenin for effective drug delivery. J Incl Phenom Macrocycl Chem. 2010;67(3-4):253-60. doi: 10.1007/s10847-009-9705-8.

  19. Rajhard S, Hladnik L, Vicente FA, Srcic S, Grilc M, Likozar B. Solubility of luteolin and other polyphenolic compounds in water, nonpolar, polar aprotic and protic solvents by applying ftir/hplc. Processes. 2021;9(11). doi: 10.3390/pr9111952.

  20. Suresh K, Nangia A. Curcumin: pharmaceutical solids as a platform to improve solubility and bioavailability. Cryst Eng Comm. 2018;20(24):3277-96, doi: 10.1039/C8CE00469B.

  21. Lu M, Ho CT, Huang Q. Improving quercetin dissolution and bioaccessibility with reduced crystallite sizes through media milling technique. J Funct Foods. 2017;37:138-46. doi: 10.1016/j.jff.2017.07.047.

  22. Zhao G, Zeng Q, Zhang S, Zhong Y, Wang C, Chen Y. Effect of carrier lipophilicity and preparation method on the properties of andrographolide–solid dispersion. Pharmaceutics. 2019;11(2). doi: 10.3390/pharmaceutics11020074.

  23. Ren S, Liu M, Hong C, Li G, Sun J, Wang J. The effects of pH, surfactant, ion concentration, coformer, and molecular arrangement on the solubility behavior of myricetin cocrystals. Acta Pharm Sin B. 2019;9(1):59-73. doi: 10.1016/j.apsb.2018.09.008. PMID 30766778.

  24. Pan H, Wang HB, Yu YB, Cheng BC, Wang XY, Li Y. Original research paper. A superior preparation method for daidzein-hydroxypropyl-β-cyclodextrin complexes with improved solubility and dissolution: supercritical fluid process. Acta Pharm. 2017;67(1):85-97. doi: 10.1515/acph-2017-0005, PMID 28231046.

  25. Jha DK, Shah DS, Amin PD. Thermodynamic aspects of the preparation of amorphous solid dispersions of naringenin with enhanced dissolution rate. Int J Pharm. 2020;583(Apr):119363. doi: 10.1016/j.ijpharm.2020.119363. PMID 32334068.

  26. Alshehri S, Imam SS, Altamimi MA, Hussain A, Shakeel F, Elzayat E. Enhanced dissolution of luteolin by solid dispersion prepared by different methods: physicochemical characterization and antioxidant activity. ACS Omega. 2020;5(12):6461-71. doi: 10.1021/acsomega.9b04075, PMID 32258881.

  27. Atun S. Characterization of nanoparticles produced by chloroform fraction of Kaempferia rotunda rhizome loaded with alginic acid and chitosan and its biological activity test. Asian J Pharm Clin Res. 2017;10(5):399-403. doi: 10.22159/ajpcr.2017.v10i5.16936.

  28. Da Silva FLO, Marques MBF, Kato KC, Carneiro G. Nanonization techniques to overcome poor water-solubility with drugs. Expert Opin Drug Discov. 2020;15(7):853-64. doi: 10.1080/17460441.2020.1750591, PMID 32290727.

  29. GOKUL M, GU, Esakki A. Green synthesis and characterization of isolated flavonoid mediated copper nanoparticles by using Thespesia populnea Leaf extract and its evaluation of an anti-oxidant and anti-cancer activity. Int J Chem Res. 2022;6(1):15-32. doi: 10.22159/ijcr.2022v6i1.197.

  30. Kaialy W, Al Shafiee M. Recent advances in the engineering of nanosized active pharmaceutical ingredients: promises and challenges. Adv Colloid Interface Sci. 2016;228:71-91. doi: 10.1016/j.cis.2015.11.010. PMID 26792017.

  31. Chu KR, Lee E, Jeong SH, Park ES. Effect of particle size on the dissolution behaviors of poorly water-soluble drugs. Arch Pharm Res. 2012;35(7):1187-95. doi: 10.1007/s12272-012-0709-3, PMID 22864741.

  32. Masserini M. Nanoparticles for brain drug delivery. ISRN Biochem. 2013;2013:238428. doi: 10.1155/2013/238428, PMID 25937958.

  33. Mc Carthy DJ, Malhotra M, O’Mahony AM, Cryan JF, O’Driscoll CM. Nanoparticles and the blood-brain barrier: advancing from in vitro models towards therapeutic significance. Pharm Res. 2015;32(4):1161-85. doi: 10.1007/s11095-014-1545-6, PMID 25446769.

  34. Ubaidulla U, Sinha P, Rathnam G. Recent update on liposome-based drug delivery system. Charumathy A. Int J Curr Pharm Res. 2022;14(3):22-7.

  35. Tiwari R, Siddiqui MH, Mahmood T, Farooqui A, Tiwari M, Shariq M. Solubility enhancement of curcumin, quercetin and rutin by solid dispersion method. AP. 2021;10(2):462-71. doi: 10.21276/ap.2021.10.2.61.

  36. Nurjanah N, Saepudin E. Curcumin isolation, synthesis and characterization of curcumin isoxazole derivative compound. AIP Conf Proc. 2019;2168.

  37. Kumari J, Chaurasia L. Formulation and evaluation of curcumin loaded nanoliposome on brain targeted. Curr Res Pharm Sci. 2021;11(1):31-43. doi: 10.24092/CRPS.2021.110104.

  38. Naseri N, Valizadeh H, Zakeri Milani P. Solid lipid nanoparticles and nanostructured lipid carriers: structure, preparation and application. Adv Pharm Bull. 2015;5(3):305-13. doi: 10.15171/apb.2015.043, PMID 26504751.

  39. Duan Y, Dhar A, Patel C, Khimani M, Neogi S, Sharma P. A brief review on solid lipid nanoparticles: part and parcel of contemporary drug delivery systems. RSC Adv. 2020;10(45):26777-91. doi: 10.1039/d0ra03491f, PMID 35515778.

  40. Padalkar KV, Gaikar VG. Extraction of piperine from Piper nigrum (black pepper) by aqueous solutions of surfactant and surfactant+hydrotrope mixtures. Sep Sci Technol. 2008;43(11-12):3097-118.

  41. Meghwal M, Goswami TK. Piper nigrum and piperine: an update. Phytother Res. 2013;27(8):1121-30. doi: 10.1002/ptr.4972, PMID 23625885.

  42. Yusuf M, Khan M, Khan RA, Ahmed B. Preparation, characterization, in vivo and biochemical evaluation of brain targeted piperine solid lipid nanoparticles in an experimentally induced Alzheimer’s disease model. J Drug Target. 2013;21(3):300-11. doi: 10.3109/1061186X.2012.747529, PMID 23231324.

  43. Bose A, Roy Burman DR, Sikdar B, Patra P. Nanomicelles: types, properties and applications in drug delivery. IET Nanobiotechnology. 2021;15(1):19-27. doi: 10.1049/nbt2.12018, PMID 34694727.

  44. Tawfik SM, Azizov S, Elmasry MR, Sharipov M, Lee YI. Recent advances in nanomicelles delivery systems. Nanomaterials (Basel). 2020;11(1):1-36. doi: 10.3390/nano11010070, PMID 33396938.

  45. Srinivas K, King JW, Howard LR, Monrad JK. Solubility and solution thermodynamic properties of quercetin and quercetin dihydrate in subcritical water. J Food Eng. 2010;100(2):208-18. doi: 10.1016/j.jfoodeng.2010.04.001.

  46. Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Rev. 2016;10(20):84-9. doi: 10.4103/0973-7847.194044, PMID 28082789.

  47. Patra A, Satpathy S, Shenoy AK, Bush JA, Kazi M, Hussain MD. Formulation and evaluation of mixed polymeric micelles of quercetin for treatment of breast, ovarian, and multidrug-resistant cancers. Int J Nanomedicine. 2018;13:2869-81. doi: 10.2147/IJN.S153094, PMID 29844670.

  48. Tabatabaei Mirakabad FST, Nejati Koshki K, Akbarzadeh A, Yamchi MR, Milani M, Zarghami N. PLGA-based nanoparticles as cancer drug delivery systems. Asian Pacific Journal of Cancer Prevention. 2014;15(2):517-35. doi: 10.7314/APJCP.2014.15.2.517.

  49. Jo A, Ringel Scaia VM, McDaniel DK, Thomas CA, Zhang R, Riffle JS. Fabrication and characterization of PLGA nanoparticles encapsulating large CRISPR-Cas9 plasmid. J Nanobiotechnology. 2020;18(1):1–14. doi: 10.1186/s12951-019-0564-1, PMID 31959180.

  50. Anwer MK, Al-Mansoor MA, Jamil S, Al-Shdefat R, Ansari MN, Shakeel F. Development and evaluation of PLGA polymer-based nanoparticles of quercetin. Int J Biol Macromol. 2016;92:213-9. doi: 10.1016/j.ijbiomac.2016.07.002. PMID 27381585.

  51. Shinkar DM, Patil AN, Saudagar RB. Review article: solubility enhancement by solid dispersion. Asian J Pharm Technol. 2017;7(2):72. doi: 10.5958/2231-5713.2017.00011.3.

  52. Allawadi D, Singh N, Singh S, Arora S. ChemInform abstract: solid dispersions: a review on drug delivery system and solubility enhancement. ChemInform. 2014;45(18). doi: 10.1002/chin.201418290.

  53. Huang Y, Dai WG. Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm Sin B. 2014;4(1):18-25. doi: 10.1016/j.apsb.2013.11.001. PMID 26579360.

  54. Sharma KS, Sahoo J, Agrawal S, Kumari A. Solid dispersions: a technology for improving bioavailability. JAPLR. 2019;8(4):127-33. doi: 10.15406/japlr.2019.08.00326.

  55. Adwan S, Shubair M. Enhancement of curcumin solubility using a novel solubilizing polymer Soluplus®. J Pharm Innov. 2020.

  56. Gangurde AB, Kundaikar HS, Javeer SD, Jaiswar DR, Degani MS, Amin PD. Enhanced solubility and dissolution of curcumin by a hydrophilic polymer solid dispersion and its insilico molecular modeling studies. J Drug Deliv Sci Technol. 2015;29:226-37. http://dx.doi:/j.jddst.2015.08.005.

  57. Li B, Konecke S, Wegiel LA, Taylor LS, Edgar KJ. Both the solubility and chemical stability of curcumin are enhanced by solid dispersion in cellulose derivative matrices. Carbohydr Polym. 2013;98(1):1108-16. doi: 10.1016/j.carbpol. 2013.07.017, PMID 23987452.

  58. Kumavat S, Chaudhari Y, Borole P, Shenghani K, Badhe M. Enhancement of solubility and dissolution rate of curcumin by solid dispersion technique. Int Res J Pharm. 2013;4(5):226-32. doi: 10.7897/2230-8407.04548.

  59. Thenmozhi K, Yoo YJ. Enhanced solubility of piperine using hydrophilic carrier-based potent solid dispersion systems. Drug Dev Ind Pharm. 2017;43(9):1501-9. doi: 10.1080/ 03639045.2017.1321658, PMID 28425323.

  60. Sari R, Setyawan D, Retnowati D, Pratiwi R. Development of andrographolide-chitosan solid dispersion system: physical characterization, solubility, and dissolution testing Retno. Asian J Pharm. 2019;13(1).

  61. Zhang D, Lin J, Zhang F, Han X, Han L, Yang M. Preparation and evaluation of andrographolide solid dispersion vectored by silicon dioxide. Pharmacogn Mag. 2016;12(46 Suppl 2):245-52. doi: 10.4103/0973-1296.182156, PMID 27279715.

  62. Setyawan D, Fadhil AA, Juwita D, Yusuf H, Sari R. Enhancement of solubility and dissolution rate of quercetin with solid dispersion system formation using hydroxypropyl methylcellulose matrix Dwi. Thai J Pharm Sci. 2017;41(3):1-5.

  63. Muresan Pop M, Pop MM, Borodi G, Todea M, Nagy Simon T, Simon S. Solid dispersions of myricetin with enhanced solubility: formulation, characterization and crystal structure of stability-impeding myricetin monohydrate crystals. J Mol Struct. 2017;1141:607-14. doi: 10.1016/ j.molstruc.2017.04.015.

  64. Loftsson T. Drug solubilization by complexation. Int J Pharm. 2017;531(1):276-80. doi: 10.1016/j.ijpharm.2017.08.087, PMID 28842309.ijpharm.2017.08.087.

  65. Choudhury H, Gorain B, Madheswaran T, Pandey M, Kesharwani P, Tekade RK. Drug complexation: implications in drug solubilization and oral bioavailability enhancement. Implications in drug solubilization and oral bioavailability. Enhancement Book Company. Dosage Form Design Considerations: 2018. p. 473-512. doi: 10.1016/B978-0-12-814423-7.00014-9.

  66. Jurca T, Marian E, Vicaş LG, Mureşan ME, Fritea L. Metal complexes of pharmaceutical substances. Spectrosc Anal-Dev Appl; 2017.

  67. Altundag EM, Ozbilenler C, Usturk S, Kerkuklu NR, Afshani M, Yilmaz E. Metal-based curcumin and quercetin complexes: cell viability, ROS production and antioxidant activity. J Mol Struct. 2021;1245. doi: 10.1016/j.molstruc.2021.131107.

  68. Telange DR, Patil AT, Pethe AM, Fegade H, Anand S, Dave VS. Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential. Eur J Pharm Sci. 2017;108:36-49. doi: 10.1016/j.ejps.2016.12.009. PMID 27939619.

  69. Chaudhary VB, Pharmacy SS. Cyclodextrin inclusion complex to enhance the solubility of poorly water-soluble drugs: a review. Int J Pharm Sci Res. 2013;4(1):68-76.

  70. Salehi B, Fokou PVT, Sharifi Rad M, Zucca P, Pezzani R, Martins N. The therapeutic potential of naringenin: a review of clinical trials. Pharmaceuticals (Basel). 2019;12(1):1-18. doi: 10.3390/ph12010011, PMID 30634637.

  71. Semalty A, Tanwar YS, Semalty M. Preparation and characterization of cyclodextrin inclusion complex of naringenin and critical comparison with phospholipid complexation for improving solubility and dissolution. J Therm Anal Calorim. 2014;115(3):2471-8. doi: 10.1007/s10973-013-3463-y.

  72. Alshehri S, Imam SS, Hussain A, Altamimi MA. Formulation of piperine ternary inclusion complex using β CD and HPMC: physicochemical characterization, molecular docking, and antimicrobial testing. Processes. 2020;8(11). doi: 10.3390/pr8111450.

  73. Liu K, Liu H, Li Z, Li W, Li L. In vitro dissolution study on the inclusion complex of piperine with ethylenediamine-β-cyclodextrin. J Incl Phenom Macrocycl Chem. 2020;96(3-4):233-43. doi: 10.1007/s10847-020-00980-5.

  74. Radjaram A, Hafid AF, Setyawan D. Dissolution enhancement of curcumin by hydroxypropyl-β-cyclodextrin complexation. Int J Pharm Pharm Sci. 2013;5(Suppl 3):401-5.

  75. Patil RB, Limbhore DN, Vanjari SS, Chavan MC. Study of solubility enhancement of quercetin by inclusion complexation with beta-cyclodextrin. J Pharm Sci Res. 2019;11(9):3102-7.

  76. Yao Y, Xie Y, Hong C, Li G, Shen H, Ji G. Development of a myricetin/hydroxypropyl-β-cyclodextrin inclusion complex: preparation, characterization, and evaluation. Carbohydr Polym. 2014;110:329-37. doi: 10.1016/j.carbpol.2014.04.006. PMID 24906763.

  77. Lujan Medina GA, Ventura J, Ascacio Valdes JA, Cerqueira MA, Villa DB, Contreras Esquivel JC. Microencapsulation of ellagic acid from pomegranate husk and karaya gum by spray drying. Int J Pharm Pharm Sci. 2015;7:10-3.

  78. Suganya V, Anuradha V. Microencapsulation and nanoencapsulation: a review. Int J Pharm Clin Res. 2017;9(3):233-9. doi: 10.25258/ijpcr.v9i3.8324.

  79. Yang X, Shen J, Liu J, Yang Y, Hu A, Ren N. Spray-drying of hydroxypropyl β-cyclodextrin microcapsules for co-encapsulation of resveratrol and piperine with enhanced solubility. Crystal. 2022;12;(596)12(5). doi: 10.3390/ cryst12050596.

  80. Tomaro Duchesneau C, Saha S, Malhotra M, Kahouli I, Prakash S. Microencapsulation for the therapeutic delivery of drugs, live mammalian and bacterial cells, and other biopharmaceutics: current status and future directions. J Pharm (Cairo). 2013;2013:103527. doi: 10.1155/2013/103527. PMID 26555963.

  81. Paolino D, Vero A, Cosco D, Pecora TMG, Cianciolo S, Fresta M. Improvement of oral bioavailability of curcumin upon microencapsulation with methacrylic copolymers. Front Pharmacol. 2016;7(Dec):1–9485. doi: 10.3389/ fphar.2016.00485, PMID 28066239.

  82. Liu JY, Zhang X, Tian BR. Selective modifications at the different positions of cyclodextrins: a review of strategies. Turkish J Chem. 2020;44(2):261-78. doi: 10.3906/kim-1910-43, PMID 33488156.

  83. Wupper S, Luersen K, Rimbach G. Cyclodextrins, natural compounds, and plant bioactives-a nutritional perspective. Biomolecules. 2021;11(3):1-21. doi: 10.3390/biom11030401, PMID 33803150.

  84. Davis ME, Brewster ME. Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov. 2004;3(12):1023-35. doi: 10.1038/nrd1576, PMID 15573101.

  85. Mai NNS, Nakai R, Kawano Y, Hanawa T. Enhancing the solubility of curcumin using a solid dispersion system with hydroxypropyl-β-cyclodextrin prepared by grinding, freeze-drying, and common solvent evaporation methods. Pharmacy (Basel). 2020;8(2034):14. doi: 10.3390/pharmacy8040203, PMID 33147710.

  86. Syed HK, Peh KK. Comparative curcumin solubility enhancement study of β-cyclodextrin (βCD) and its derivative hydroxypropyl-β-cyclodextrin (HPβCD). Lat Am J Pharm. 2013;32(1):52-9.

  87. Li N, Wang N, Wu T, Qiu C, Wang X, Jiang S. Preparation of curcumin-hydroxypropyl-β-cyclodextrin inclusion complex by cosolvency-lyophilization procedure to enhance oral bioavailability of the drug. Drug Dev Ind Pharm. 2018;44(12):1966-74. doi: 10.1080/03639045.2018.1505904, PMID 30059244.

  88. Nagy NZ, Varga Z, Mihaly J, Domjan A, Fenyvesi eva, Kiss eva Nagy NZ, Varga Z, Mihaly J, Domjan A, Fenyvesi E, Kiss E. Highly enhanced curcumin delivery applying association type nanostructures of block copolymers, cyclodextrins and polycyclodextrins. Polymers (Basel). 2020;12(9). doi: 10.3390/polym12092167, PMID 32971985.

  89. Teodorescu M, Bercea M. Poly(vinylpyrrolidone)–A versatile polymer for biomedical and beyond medical applications. Polym Plast Technol Eng. 2015;54(9):923-43. doi: 10.1080/03602559.2014.979506.

  90. Mireles LK, Wu MR, Saadeh N, Yahia L, Sacher E. Physicochemical characterization of polyvinyl pyrrolidone: A tale of two polyvinyl pyrrolidones. ACS Omega. 2020;5(47):30461-7. doi: 10.1021/acsomega.0c04010, PMID 33283094.

  91. Kurakula M, Rao GSNK. Pharmaceutical assessment of polyvinylpyrrolidone (PVP): as excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition. J Drug Deliv Sci Technol. 2020;60:102046. doi: 10.1016/j.jddst.2020.102046, PMID 32905026.

  92. Zhang S, Zhang X, Meng J, Lu L, Du S, Xu H. Study on the effect of polymer excipients on the dispersibility, interaction, solubility, and scavenging reactive oxygen species of myricetin solid dispersion: experiment and molecular simulation. ACS Omega. 2022;7(1):1514-26. doi: 10.1021/acsomega.1c06329, PMID 35036814.

  93. Feng B lu, Li H wen, Zhou M yao, Lu W. Dispersion of daidzein with polyvinylpyrrolidone effects on dissolution rate and bioavailability. Zhong Yao Cai. 2011 Apr;34(4):605–10.

  94. Majumder T, Biswas GR, Majee SB. Hydroxypropyl methylcellulose: different aspects in drug delivery. J Pharm Pharmacol. 2016;4(8).

  95. Maskova E, Kubova K, Raimi-Abraham BT, Vllasaliu D, Vohlídalova E, Turanek J. Hypromellose-a traditional pharmaceutical excipient with modern applications in oral and oromucosal drug delivery. J Control Release. 2020 May;324:695-727. doi: 10.1016/j.jconrel.2020.05.045, PMID 32479845.

  96. Yu JY, Kim JA, Joung HJ, Ko JA, Park HJ. Preparation and characterization of curcumin solid dispersion using HPMC. J Food Sci. 2020;85(11):3866-73. doi: 10.1111/1750-3841.15489, PMID 33067846.

  97. Hutanu D. Recent applications of polyethylene glycols (PEGs) and PEG derivatives. Mod Chem Appl. 2014;2(02). doi: 10.4172/2329-6798.1000132.

  98. Zarrintaj P, Saeb MR, Jafari SH, Mozafari M. Application of compatibilized polymer blends in biomedical fields. Elsevier Inc; 2019. p. 511-37.

  99. Dwi S, Febrianti S, Zainul A, Retno SFebrianti S, Zainul A, Retno S, Dwi S. PEG 8000 increases solubility and dissolution rate of quercetin in solid dispersion system. Marmara Pharm J. 2018;22(2):259-66. doi: 10.12991/mpj.2018.63.

  100. Muxika A, Etxabide A, Uranga J, Guerrero P, de la Caba K. Chitosan as a bioactive polymer: processing, properties and applications. Int J Biol Macromol. 2017;105(2):1358-68. doi: 10.1016/j.ijbiomac.2017.07.087, PMID 28735006.

  101. Kumar D, Gihar S, Shrivash MK, Kumar P, Kundu PP. A review on the synthesis of graft copolymers of chitosan and their potential applications. Int J Biol Macromol. 2020;163:2097-112. doi: 10.1016/j.ijbiomac.2020.09.060, PMID 32949625. ijbiomac.2020.09.060.

  102. Aranaz I, Alcántara AR, Civera MC, Arias C, Elorza B, Heras Caballero AH, et al. Chitosan: an overview of its properties and applications. Polymers (Basel). 2021;13(19). doi: 10.3390/polym13193256, PMID 34641071.

  103. Kahya N.. Water Ssoluble Cchitosan Dderivatives and their Biological Aactivities: Aa Rreview. Polym Sci.. 2019;05(01):1-11. doi: 10.36648/2471-9935.5.1.44.

  104. Wong JJL, Yu H, Hadinoto K. Examining practical feasibility of amorphous curcumin-chitosan nanoparticle complex as solubility enhancement strategy of curcumin: Scaled-up production, dry powder transformation, and long-term physical stability. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2018;537:36-43. doi: 10.1016/j.colsurfa.2017.10.004.

  105. Bhilegaonkar S, Parvatkar A. Eudragit: a versatile and robust platform. Int J Pharm Sci Res. 2020;11(6):2626-35. doi: 10.13040/IJPSR.0975-8232.11.

  106. Kapoor DN, Bhatia A, Kaur R, Sharma R, Kaur G, Dhawan S. PLGA: A unique polymer for drug delivery. Ther Deliv. 2015;6(1):41-58. doi: 10.4155/tde.14.91, PMID 25565440.

  107. Anwer MK, Al-Mansoor MA, Jamil S, Al-Shdefat R, Ansari MN, Shakeel F. Development and evaluation of PLGA polymer-based nanoparticles of quercetin. Int J Biol Macromol. 2016 Jul 1;92:213-9. doi: 10.1016/j.ijbiomac.2016.07.002, PMID 27381585.

  108. Linn M, Collnot EM, Djuric D, Hempel K, Fabian E, Kolter K. Soluplus® as an effective absorption enhancer of poorly soluble drugs in vitro and in vivo. Eur J Pharm Sci. 2012;45(3):336-43. doi: 10.1016/j.ejps.2011.11.025, PMID 22172603.