**4. Application of the practical use of hydrogels based on copolymers of PVP and (meth)acrylates**

## **4.1. Sorption-active granular copolymers of methacrylic acid esters with polyvinylpyrrolidone [60]**

**Figure 4.** Adsorption of water by PVP from the atmosphere (25°С) for 7 days.

34 Hydrogels

**Figure 5.** Adsorption and desorption of water by PVP from atmosphere (25°С) [58].

PHEMA 115 4 8 80 212/242\* PVP-gr-PHEMA 550 0 0 2 848/865\* Methyl cellulose 126 8 5 95 −

**Heparin desorption for 24 h (%) КNaCl. 105 (mole·m−2·h−1 рН = 2.7 рН = 7 рН = 9.1 )**

for heparinized membranes.

**(10−3 u/m2 )**

Comments: *δ* = 200 μm; КNaCl is a permeability coefficient for NaCl; \*

**Table 10.** Heparin immobilization by membrane surface and their permeability.

**Material of membranes Heparin sorption**

Granular copolymerization of 2-hydroxyethyl methacrylate and glycidyl methacrylate with polyvinylpyrrolidone in inert solvents was studied. In suspension (co)polymerization of HEMA with PVP using both PVP and PVA, as stabilizers and also magnesium hydroxide, we obtained spherical particles of satisfactory polydispersity.

The copolymers synthesized are promising as polymer systems for prolonged and controlled drug release. Spherical polymeric particles of size 0.25…2 mm were prepared by suspension copolymerization of the formulations of 2-hydroxyethyl methacrylate and glycidyl methacrylate with polyvinylpyrrolidone. The size and polydispersity of the particles can be controlled by varying the process parameters. The copolymers synthesized exhibit an increased ability to sorb anionic substances, with their subsequent prolonged release in alkaline medium. The composition and particle size of the (co)polymers determine the fields of their application and their performance in prolonged drug release systems.

We researched the effect of the main component ratio of the initial composition on sorptiondesorption properties of the granulated polymers based on the results shown in **Figure 6**.

As seen from the obtained results, the lowest observed sorption capacity have homopolymers based on HEMA (**Figure 6**, curve 1). And, efficient sorption has been observed in the first 4 h of the process and continue virtually unchanged. The granulated drug carriers of "Sferogel" provide an effective control of release at a constant rate during the first 8…1 h (**Figure 7**, curve 2).

**Figure 6.** The kinetic curves of diclofenac sodium sorption (G) by granulated hydrogel polymer (SG): HEMA:PVP, wt. p.: (1) 10:0 (SG-1); (2) 8:2 (SG-2); (3) 7:3 (SG-3); dev. = 640 μm.

pH=2.7, physiological solution with pH = 7, and solution of sodium tetraboric acid with pH = 9.1). Here, the selective transport characteristics of membranes are changed insignificantly. As for membranes based on polyHEMA and modified cellulose, there is an insignificant precipitation of anticoagulant in acid and neutral media, while in alkaline medium, it

We have established that the presence of –OH and N–C = O hydrophilic groups in the composition of membrane copolymers increases their sorption ability which is characterized with water content (**Table 11**). The increase of PVP content multiplies dialysis permeability (КNaCl) of hydrogel membranes based on HEMA/PVP, but their strength falls down (**Table 11**). Hence, changing hydrogel chemical structure, it is possible to change permeability of mem-

At the same time, the hydrogel membranes based on HEMA/PVP copolymers have higher sorption properties compared with HEMA copolymers and higher penetrability for water

It is interesting that the mass between cross-links does not directly depend upon the solvent polarity. One would expect such a dependence of the given "loosing" effect on the PVP molecules. However, when the solvent amount exceeds its maximum sorption by the polymeric matrix at

Thus, the control of the initial mixture composition via complex formation is an effective method of structure and penetration control for hydrogel membranes based on hydroxyalkyl methacrylates and polyvinylpyrrolidone. Membranes may be recommended for encapsulation and creation of prolonged forms of drug's controlled release and hemodialysis, as well as for fractionating and concentrating of high molecular mass compounds, including biological

**Water content**

Hydrogels Based on Polyvinylpyrrolidone Copolymers http://dx.doi.org/10.5772/intechopen.72082 37

**КNaCl**

**(%)**

swelling equilibrium, the already mentioned phase separation occurs (**Table 12**).

**(MPa)**

 — 0.53 40 127 9 0.46 45 293 18 0.40 48 412 23 0.31 53 506 31 0.22 61 611

**(mole·m−2·h−1) HEMA PVP**

grows to 80…95%.

**polyvinylpyrrolidone [63]**

media.

branes on the basis of HEMA/PVP copolymers.

**4.3. Hydrogel membranes based on cross-linked copolymers of** 

and several low molecular mass compounds (**Table 12**).

**Contents of the components (mass parts) Membrane tensile strength** 

Comments: δ = 200 μm; КNaCl is a permeability coefficient for NaCl.

**Table 11.** Properties of hydrogel membranes based on HEMA/PVP.

**Figure 7.** Kinetic curves of diclofenac sodium desorption: (1) for film composite materials filled with SG (HEMA:PVP:SG-2:H<sup>2</sup> O = 8:2:1:15 wt. p.) and (2) for SG-2.

If the granules are placed in a hydrogel film, the induction period of 1 h is observed during release when the drugs diffuse from the granules through the film; then, the stable and prolonged release takes place into the environment during the day (**Figure 7**, curve 1).

#### **4.2. High-hydrophilic and thromboresistive dialysis membranes [61, 62]**

Development of hemodialysis membranes, cardiovascular implants, and other artificial organs put forward the problem of thromboresistive material creation. One of the effective ways of thromboresistance increase is immobilization of heparin, which is a natural blood anticoagulant, over material surface. The main problem of heparin immobilization by polymeric membranes is its permanent minimal desorption at a contact with blood.

Netted of HEMA/PVP copolymers are perspective compounds for the production of dialysis membranes. The presence of PVP ionic groups in the composition of mentioned copolymers assumes the expansion of biochemical and sorption characteristics and obtaining of membranes with additional functions on their basis.

Hydrogel membranes were obtained by graft polymerization of НЕМА over PVP (molecular mass was 10…50⋅103 ) in an aqueous medium, which allowed to combine the synthesis stage and membrane swelling. The saturation of membranes with heparin was realized in glycerol buffer solution (1 M glycerin solution, pH = 2.7), which contained 250,000 units of heparin in 1 l. The amount of sorbed and desorbed heparin was determined by photocolorimetry, based on quantitative determination of heparin and methylene blue complex. Synthesized hydrogel membranes with PVP links have advanced the immobilization ability relative to heparin (**Table 10**).

PVP–heparin complex is so strong, that heparin does not desorb for 24 hours (see Table 10) from the membranes keeping in solutions with different pH (glycin buffer solution with pH=2.7, physiological solution with pH = 7, and solution of sodium tetraboric acid with pH = 9.1). Here, the selective transport characteristics of membranes are changed insignificantly. As for membranes based on polyHEMA and modified cellulose, there is an insignificant precipitation of anticoagulant in acid and neutral media, while in alkaline medium, it grows to 80…95%.

We have established that the presence of –OH and N–C = O hydrophilic groups in the composition of membrane copolymers increases their sorption ability which is characterized with water content (**Table 11**). The increase of PVP content multiplies dialysis permeability (КNaCl) of hydrogel membranes based on HEMA/PVP, but their strength falls down (**Table 11**). Hence, changing hydrogel chemical structure, it is possible to change permeability of membranes on the basis of HEMA/PVP copolymers.

## **4.3. Hydrogel membranes based on cross-linked copolymers of polyvinylpyrrolidone [63]**

If the granules are placed in a hydrogel film, the induction period of 1 h is observed during release when the drugs diffuse from the granules through the film; then, the stable and pro-

**Figure 7.** Kinetic curves of diclofenac sodium desorption: (1) for film composite materials filled with SG (HEMA:PVP:SG-

Development of hemodialysis membranes, cardiovascular implants, and other artificial organs put forward the problem of thromboresistive material creation. One of the effective ways of thromboresistance increase is immobilization of heparin, which is a natural blood anticoagulant, over material surface. The main problem of heparin immobilization by poly-

Netted of HEMA/PVP copolymers are perspective compounds for the production of dialysis membranes. The presence of PVP ionic groups in the composition of mentioned copolymers assumes the expansion of biochemical and sorption characteristics and obtaining of mem-

Hydrogel membranes were obtained by graft polymerization of НЕМА over PVP (molecular

and membrane swelling. The saturation of membranes with heparin was realized in glycerol buffer solution (1 M glycerin solution, pH = 2.7), which contained 250,000 units of heparin in 1 l. The amount of sorbed and desorbed heparin was determined by photocolorimetry, based on quantitative determination of heparin and methylene blue complex. Synthesized hydrogel membranes with PVP links have advanced the immobilization ability relative to heparin

PVP–heparin complex is so strong, that heparin does not desorb for 24 hours (see Table 10) from the membranes keeping in solutions with different pH (glycin buffer solution with

) in an aqueous medium, which allowed to combine the synthesis stage

longed release takes place into the environment during the day (**Figure 7**, curve 1).

**4.2. High-hydrophilic and thromboresistive dialysis membranes [61, 62]**

meric membranes is its permanent minimal desorption at a contact with blood.

branes with additional functions on their basis.

mass was 10…50⋅103

(**Table 10**).

2:H<sup>2</sup>

36 Hydrogels

O = 8:2:1:15 wt. p.) and (2) for SG-2.

At the same time, the hydrogel membranes based on HEMA/PVP copolymers have higher sorption properties compared with HEMA copolymers and higher penetrability for water and several low molecular mass compounds (**Table 12**).

It is interesting that the mass between cross-links does not directly depend upon the solvent polarity. One would expect such a dependence of the given "loosing" effect on the PVP molecules. However, when the solvent amount exceeds its maximum sorption by the polymeric matrix at swelling equilibrium, the already mentioned phase separation occurs (**Table 12**).

Thus, the control of the initial mixture composition via complex formation is an effective method of structure and penetration control for hydrogel membranes based on hydroxyalkyl methacrylates and polyvinylpyrrolidone. Membranes may be recommended for encapsulation and creation of prolonged forms of drug's controlled release and hemodialysis, as well as for fractionating and concentrating of high molecular mass compounds, including biological media.


**Table 11.** Properties of hydrogel membranes based on HEMA/PVP.


copolymer composition for contact lenses. It allowed to manufacture correctional soft contact

**Figure 8.** The scheme of component transfer from encapsulated particles: (1) dosage form, (2) hard polymeric shell, (3)

Hydrogels Based on Polyvinylpyrrolidone Copolymers http://dx.doi.org/10.5772/intechopen.72082 39

Good permeability for a series of substances, including medicinal solutions, compatibility with alive tissues, and acceptability, has caused the use of the synthesized copolymers for medical ophthalmologic elements of the various geometric shapes. Significant advantage of contact lenses based on PVP copolymer is an essential retention of UV rays and increased oxygen permeability. It provides the lens comfort while long staying on the eye's cornea.

The comparative clinical tests of a condition of an acuteness of vision of an eye without correction and portable spectacle correction were carried out in Lviv Railway Clinical Hospital. From 163 patients without having correction of an acuteness of vision less 0.1 after corrections by contact lenses, an acuteness of vision has increased more than in 80% and has made 0.85– 1.0. Researches of a condition of an epithelial integument of a cornea carried out in a various lines after acclimatization at all patients have shown that infringement of integrity of a cornea epithelium does not occur. And, only at six patients after long continuous application of lenses

In this, application of soft hydrophilic contact lenses in treatment of eye diseases is a new promising approach. It substitutes surgical methods in treatment of burns, prevents a symblepharon formation, allows a late keratoplastic, improves results, and decreases treatment duration with

lenses "Akrylan-LPI" with the following operational properties (**Table 13**).

swollen hydrogel, (4) release of dosage form, and (5) used capsule.

(more than 3 days), mild inflammation of an epithelium was observed.

**Properties in hydrated condition Parameter meaning**

**Table 13.** The characteristics of a polymeric material for soft contact lenses "Akrylan-LPI".

⋅s−1) 1.2

⋅m−2⋅h−1) 52

Absorption of water (%) 51

NaCl permeability (mole⋅m−2⋅s−1) 180 Toughness at a stretching (МPа) 0.4 Relative tensile elongation (%) 250 Permeability of light (%) 96 Refraction index (nD) 1.4253

high social and economic impact.

m3

Oxygen permeability (×1010 m2

Water permeability (×104

Comments: \* for *δ* = 200 μm; K, coefficient of water permeability; optical transmission coefficient is 90–96% for experiments 1–5, 8, and 9; opaque membranes have been obtained in experiments 6 and 7.

**Table 12.** Sorption-diffusion properties of hydrogel membranes.

## **4.4. Polyvinylpyrrolidone cross-linked copolymers for capsulated particles of drugs [64, 65]**

Copolymers synthesized in the form of membranes were effective capsulated agents of solid drugs. In dry state, while storing, they act as protective envelope, but while operation they are able to swell in the physical solution and become permeable. The transferring mechanism of components, including drugs, from encapsulated particles involves several stages (**Figure 8**):


The used capsule is excreted naturally, without causing any collateral damage to the body.

We also examined the drug release by spherical particles because they model the behavior of prolonged drug while operation.

Thus, we established the relationship between synthesis conditions, structure, and sorptiondesorption properties of PVP cross-linked copolymers, what offers their application as carriers for the systems of drug's directional and controlled release.

#### **4.5. Soft contact lenses [66]**

It should be noted that the change of the structure and composition of copolymers may considerably influence the size of refraction index nD. This was consequently used for optimization of

**Figure 8.** The scheme of component transfer from encapsulated particles: (1) dosage form, (2) hard polymeric shell, (3) swollen hydrogel, (4) release of dosage form, and (5) used capsule.

copolymer composition for contact lenses. It allowed to manufacture correctional soft contact lenses "Akrylan-LPI" with the following operational properties (**Table 13**).

Good permeability for a series of substances, including medicinal solutions, compatibility with alive tissues, and acceptability, has caused the use of the synthesized copolymers for medical ophthalmologic elements of the various geometric shapes. Significant advantage of contact lenses based on PVP copolymer is an essential retention of UV rays and increased oxygen permeability. It provides the lens comfort while long staying on the eye's cornea.

The comparative clinical tests of a condition of an acuteness of vision of an eye without correction and portable spectacle correction were carried out in Lviv Railway Clinical Hospital. From 163 patients without having correction of an acuteness of vision less 0.1 after corrections by contact lenses, an acuteness of vision has increased more than in 80% and has made 0.85– 1.0. Researches of a condition of an epithelial integument of a cornea carried out in a various lines after acclimatization at all patients have shown that infringement of integrity of a cornea epithelium does not occur. And, only at six patients after long continuous application of lenses (more than 3 days), mild inflammation of an epithelium was observed.

**4.4. Polyvinylpyrrolidone cross-linked copolymers for capsulated particles of drugs** 

1–5, 8, and 9; opaque membranes have been obtained in experiments 6 and 7.

**Table 12.** Sorption-diffusion properties of hydrogel membranes.

• Mass transfer through the hydrogel membrane to the surrounding solution

ers for the systems of drug's directional and controlled release.

The used capsule is excreted naturally, without causing any collateral damage to the body.

We also examined the drug release by spherical particles because they model the behavior of

Thus, we established the relationship between synthesis conditions, structure, and sorptiondesorption properties of PVP cross-linked copolymers, what offers their application as carri-

It should be noted that the change of the structure and composition of copolymers may considerably influence the size of refraction index nD. This was consequently used for optimization of

Copolymers synthesized in the form of membranes were effective capsulated agents of solid drugs. In dry state, while storing, they act as protective envelope, but while operation they are able to swell in the physical solution and become permeable. The transferring mechanism of components, including drugs, from encapsulated particles involves several stages

for *δ* = 200 μm; K, coefficient of water permeability; optical transmission coefficient is 90–96% for experiments

**[64, 65]**

Comments: \*

(**Figure 8**):

• Swelling of the hydrogel membrane

prolonged drug while operation.

**4.5. Soft contact lenses [66]**

• Molecular diffusion inside the capsule

**Contents of the components (mass parts) Water content**

**HEMA PVP Н<sup>2</sup>**

38 Hydrogels

**(%)**

 — 100 — 40 5 80 13 5 20 100 — 48 52 181 36 14 20 95 5 48 55 193 — — 20 90 10 47 57 212 — — 20 80 20 47 63 240 — — 20 200 — 55 74 234 59 30 20 300 — 61 90 263 60 31 30 100 — 53 71 232 59 30 50 100 — 61 102 274 65 33

**K**⋅**104 (m3 /m2** ⋅**h)**

**О DMSO NaCl Carbamide Saccharose**

**Penetration coefficient\***

**(mole/m2.h)**

In this, application of soft hydrophilic contact lenses in treatment of eye diseases is a new promising approach. It substitutes surgical methods in treatment of burns, prevents a symblepharon formation, allows a late keratoplastic, improves results, and decreases treatment duration with high social and economic impact.


**Table 13.** The characteristics of a polymeric material for soft contact lenses "Akrylan-LPI".

Clinical trial batch of 460 soft contact lens materials of "Akrylan-LPI" in the Laboratory of contact correction of the Filatov Institute of Eye Diseases and Tissue Therapy (Odesa) has been conducted. The comparative study on eye visual acuity, corrected with soft contact lens material "Akrylan-LPI" lenses and contact lens from polyHEMA, has been held on 180 eyes in order to evaluate the optical correction of soft contact lenses.

[5] Arbuzova IA. Andreeva GA. Sintez i svoystva polimerov monoakrilata etilenglikolya:

Hydrogels Based on Polyvinylpyrrolidone Copolymers http://dx.doi.org/10.5772/intechopen.72082 41

[7] Kaetsu Isaa, Kumakura Minoru, Ito Okhito. Soft contact lenses and process for prepara-

[8] Refojo MF, Yasuda H. Hydrogels from 2-hydroxyethyl methacrylate and propylene glycol monoacrylate. Journal of Applied Polymer Science. 1965;**9**(7):2425-2435. DOI:

[9] Migliaresi C, Nicodemo L, Nicolais L, Passerini P, Stol M, Hrouz J, Cefelin P. Water sorption and mechanical properties of 2-hydroxyethyl-methacrylate and methylmethacrylate copolymers. Journal of Biomedical Materials Research. 1984;**18**(2):137-146. DOI:

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[11] Seiderman M. Improvements in relation to the preparation of hydrophilic gel polymers:

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[21] Taruni Niro, Tuchia Makoto. Process of producing soft contact lenses: Patent USA

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[17] Loshaek S. Contact lenses of high water contact. Patent USA 4158085; 1979

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Plasticheskie massyi. 1982;**6**:46-47

10.1002/app.1965.070090707

10.1002/jbm.820180204

Great Britain Patent 1339727; 1974

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