Polyelectrolyte Complex as a Novel System for Controlling Drug Release

 

Pachare S.G.*, Shirolkar S.V. and Bhalerao A.V.

Department of Pharmaceutics, Pad. Dr. D.Y. Patil IPSR, Pimpri, Pune-18, Maharashtra, India

*Corresponding Author E-mail: snehagp30@gmail.com

 

ABSTRACT:

The study of polyelectrolyte complex (PEC) of oppositely charged polymer has great potential in the field of controlled and targeted delivery. The objective of present work was to study oppositely charged polymers by evaluating their effect on various factors of hydrogel. In proposed study, chitosan (CTN), a natural polymer of cationic nature and κ-carrageenan (CGN) and xanthan gum (XGM) polymers of anionic nature were selected and used in different polymer ratio. Complexes between oppositely charged polymers i.e. CTN-CGN and CTN-XGM were used in design to control the release of drug diclofenac potassium (DFP). The oppositely charged polymer forms PEC which controlled the release of drug from polymer matrix, as single polymer do not shows this effect. The polyelectrolyte complex (PEC) thus formed were loaded with DFP which is anionic in nature. In vitro releases of drug, viscosity of plain polymer alone and in combination were measured. When CGN existed in an aggregated helical conformation, the interaction with CTN produced PECs with a charge ratio of CTN to CGN below unity. The interactions between polymers were studied using differential scanning calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR) study. The reasons for controlled release of DFP from CTN matrices at different pH include poor aqueous solubility of drug, formation of a rate-limiting polymer gel barrier along periphery of matrices, interaction of DFP with protonated amino group of CTN, and the interaction of ionized amino group of CTN with ionized sulphate group of CGN and carboxylic group of XGMZ.

 

KEYWORDS: Anionic and cationic polymers, polyelectrolyte complex, diclofenac potassium, drug release.

 


 

1. INTRODUCTION:

The formation of complexes through binding of oppositely-charged polyelectrolytes is well known. The PECs are established by ionic interactions between two oppositely charged polyelectrolytes1,2. Recently, polyelectrolyte complexes (PEC) based on natural polysaccharides have attracted considerable attention in the pharmaceutical domain due to their potential applications in drug delivery systems3.

 

PEC gels formed by the electrostatic attraction between two oppositely charged polyelectrolyte mixed in aqueous solution are known to exhibit unique physical and chemical properties, as the electrostatic interactions within the PEC gels are considerably stronger than most secondary binding interactions4. In last decade, there has been an increasing interest in use of PEC gels formed by CTN and polyanions as carriers for drug delivery and in immobilized systems4,5.

 

A variety of PECs can be obtained by changing the chemical structure of component polymers, such as molecular weight, flexibility, functional group structure, charge density, hydrophilicity and hydrophobicity balance and compatibility, as well as reaction conditions: pH, ionic strength, concentration, mixing ratio, and temperature6.

 

Hydrogels are usually formed by the covalent cross-linking of linear hydrophilic polymers to form a network of material capable of absorbing water, yet still remaining insoluble. Heterogeneous polymer mixtures may also be used to form hydrogels without the need for covalent cross-linking7.

 

PEC is a neutral polymer-polymer complex composed of macromolecules carrying opposite charges causing them to be bound together by electrostatic interactions. Complexes between oppositely charged polyelectrolytes such as sodium alginate-chitosan, polyacrylic acid-chitosan, xanthan gum-chitosan and chitosan-carrageenan have been used in the design of controlled release matrix formulations8,9.

 

Chitosan (CTN) is the only natural cationic polymer, which is the second most abundant polymer in nature after cellulose. It is a linear co-polymer polysaccharide consisting of β (1–4)-linked 2-amino-2-deoxy-D-glucose (D-glucosamine), and is produced by alkaline deacetylation of chitin. It shows excellent biological properties such as biocompatibility, biodegradability, lack of toxicity, and adsorption, as well as relative high nitrogen content. The unique properties of CTN arise from its amino groups that carry positive charges at pH values below 6.5, which enables its binding to negatively charged materials such as enzymes, cells, polysaccharides, nucleic acids, hair and skin4.

 

Carrageenans are naturally occurring high molecular weight polysaccharides. They consist of sulphate ester of galactose and 3, 6 anhydrogalactose joined by alternating α-1, 3 and β-1, 4 glycosidic linkages. There are 3 main types of carrageenan available: iota (ι), kappa (κ) and lambda (λ), with 1, 2, or 3 ester sulphate group, respectively.

 

The highly sulphated λ-carrageenan does not gel, but both other types, ι-carrageenan and κ-carrageenan, are able to generate gels with different characteristics that can influence drug release behaviour from mixture.1,2

 

Xanthan gum (XGM) is anionic polymer, with a cellulosic backbone of D-glucose linked β-1, 4,  For every alternate glucose there is a side chain consisting of β-D-mannose-(1,4)-β-D-glucuronic acid-(1,2)-α-D-mannose. The molecular weight of XGM can reach up to 6 million Daltons, which makes it possible to create extremely viscous solutions at very low concentration. In addition to its enzymatic resistance, XGM is stable over a wide range of temperature and pH, which finds many applications in food, pharmaceutical, cosmetic, and oil-drilling industry.4,10,11

 

Diclofenac potassium (DFP) is a nonsteroidal anti-inflammatory, weakly acidic drug that contains ionizable carboxylic acid group. The drug solubility increases with an increase in pH. In the present study, an attempt has been made to study the PEC of cationic polymer CTN and anionic polymer CGN, and their effect on drug release. DFP was chosen as a model drug because of its anionic nature.7,12,13

 

Several studies are found in the literature, concerning the specific effect of some cations (K+, Rb+ and Cs+) on gelation properties of CGN while the effect of Na+ on its conformational change and aggregation is still a matter of debate. In presence of Na+, CGN is found in a coil state at room temperature whereas in the presence of K+, it can be in a coil or helix state depending on salt concentration and temperature. Potassium ions seem to bind to polymer in disordered state also[10] C. Rochas and M. Rinaudo, Mechanism of gel formation in κ-previous termCarrageenan,next term Biopolymers 23 (1984), pp. 735–745.Full Text via CrossRef. More recently, it was suggested that presence of Na+ in solution can induce a conformational transition in CGN at high salt concentration and low temperature. Finally, only few literature data concern the effects of simultaneous presence of different cations on gelation properties of CGN. Indeed, results obtained by Hermansson et al.14 suggest that addition of a mixture of K+ and Na+ ions may have a synergistic effect, although no detailed explanation is provided.15,17

 

In the present study an attempt has been made to compare the PEC formed by the two different combinations of polymers i.e. CTN-CGN and CTN-XGM and their effect on viscosity and drug release.

 

Fig 1. Percent cumulative drug release at pH 4 acetate buffer (mean±SD, n=3)

 

2. MATERIALS AND METHODS:

2.1. Materials:

Chitosan 86% deacetylation (W.C.C. International, Mumbai, India); κ-Carrageenan (Kachabo Gums, Navi Mumbai, India); Xanthan gum (Lucid Colloids Ltd., Mumbai, India); Diclofenac Potassium (Lotus International, Mumbai, India) were generous gift samples. All other chemicals were purchased and were of analytical grade.

 

2.2. Hydrogel preparation by varying solvent pH of acetate buffer (pH 4.0/ pH 5.0/ pH 6.0)

Three varying pH of acetate buffer i.e. pH 4.0, pH 5.0, and pH 6.018 were selected because CTN with ~85% of deacetylation have been found to be soluble up to pH 6.5.

 

2.2.1. Hydrogels preparation of plain polymer with and without drug

Weighed amount of polymers (as given Table 1) were added slowly in acetate buffer (pH 4.0/ pH 5.0/ pH 6.0) separately. After addition and complete dissolution of drug it was stirred slowly with help of overhead stirrer for 15 min. Total weight of gel was adjusted.


 

Table 1.  Formulation of gels with polymers alone or in combination and with or without drug

Batch

Chitosan

(CTN) (g)

κ-Carrageenan

(CGN) (g)

Xanthan Gum (XGM) (g)

Diclofenac Potassium

(DFP) (g)

Total wt  of gel (g)

CH-1

1.500

0

0

0

50

CR-1

0

1.500

0

0

50

XG-1

0

0

1.500

0

50

CH-2

1.500

0

0

0.5

50

CR-2

0

1.500

0

0.5

50

XG-2

0

0

1.500

0.5

50

CC-1

1.125

0.375

0

0

50

CC-2

0.750

0.750

0

0

50

CC-3

0.375

1.125

0

0

50

CC-4

1.125

0.375

0

0.5

50

CC-5

0.750

0.750

0

0.5

50

CC-6

0.375

1.125

0

0.5

50

CX-1

1.125

0

0.375

0

50

CX-2

0.750

0

0.750

0

50

CX-3

0.375

0

1.125

0

50

CX-4

1.125

0

0.375

0.5

50

CX-5

0.750

0

0.750

0.5

50

CX-6

0.375

0

1.125

0.5

50

 


 

Fig 2. Percent cumulative drug release at pH 5 acetate buffer (mean±SD, n=3)

 

2.2.2. Hydrogel preparation of combination of polymers with and without drug

Hydrogels of oppositely charged polymers were prepared by varying the polymer ratio of cationic polymer (i.e. CTN) and anionic polymer (i.e. CGN, XGM) the ratios were 75:25; 50:50; 25:75 for cationic and anionic polymers respectively. Required amount of polymers were weighed (as given in Table 1) and added slowly in acetate buffer (pH 4.0/ pH 5.0/ pH 6.0) separately, after addition and complete dissolution of DFP.

 

Fig 3. Percent cumulative drug release at pH 6 acetate buffer (mean±SD, n=3)

 

2.3. Viscosity measurement:

The viscosity of 3% w/v polymer mixture gels in acetate buffer pH 4, pH 5 and pH 6 were measured at 25°C. A Brookfield programmable viscometer (RVDV-II+ pro) along with helipath assembly was used to determine viscosity (in cP). The spindle used was T-bar spindle no. S93(C) at 5 rpm for 30 s run time. Readings were taken in duplicate. Table 2 describes average viscosity of polymer alone and in combination, with and without drug in different acetate buffer pH 4, pH 5 and pH 6.

 

Fig 4. IR spectral analysis of (A) diclofenac potassium, (B) chitosan, (C) κ-carrageenan, (D) xanthan gum,   (E) chitosan : κ-carrageenan, (F) chitosan: xanthan gum, (G) chitosan : diclofenac potassium, (H) κ-carrageenan : diclofenac potassium, (I) chitosan: κ-carrageenan: diclofenac potassium (J) xanthan gum: diclofenac potassium, (K) chitosan: xanthan gum: diclofenac potassium

 

 

Table 2. Viscosity of hydrogels of combination of polymers with or without drug at different pH (n=2)

Formulations

Viscosity (cP)

pH 4

pH 5

pH 6

CH-1

6800

7290

9243

CH-2

2680

4130

5969

CR-1

3642

2600

1329

CR-2

22216

15610

13319

XG-1

25650

23621

22610

XG-2

25626

23479

21462

CC-1

5692

6821

9214

CC-2

4216

5132

7121

CC-3

5134

4692

3242

CC-4

8693

10692

12219

CC-5

6368

7319

10216

CC-6

31039

21629

17316

CX-1

8216

9431

14026

CX-2

6926

7342

9246

CX-3

18504

14162

12636

CX-4

8429

9869

10216

CX-5

5942

6283

9021

CX-6

22621

20432

16219

 

2.4. In vitro drug diffusion study:

Release study of DFP was performed in triplicates for each batch using Keshary-Chein diffusion cell with receptor side volume of 27 mL. The dialysis membrane (Himedia Mol.wt.-12,000 to 14000) was soaked in phosphate buffer pH 7.4 for 24 h. The temperature was maintained at 37 ± 0.5°C with the help of hot plate. Dialysis membrane was mounted between donor and receptor compartment of diffusion cell. Hydrogel (2 g) was kept on donor side. Phosphate buffer pH 7.4 was used as receptor solution. Receptor solution was stirred with bent stainless steel pin using magnetic stirrer (500 rpm). Sample 1 mL was withdrawn at an interval of 30 min up to six hours and diluted to 5 mL. The same volume (1 mL) of phosphate buffer pH 7.4 was added to receptor compartment to maintain sink condition. Samples were filtered through Whatman filter paper 41 and drug concentration was determined spectrophotometrically at 277 nm for DFP.

 

2.5. Preparation of dried hydrogel:

The hydrogel of single polymer and combination of polymers (such as CTN-CGN and CTN-XGM) in different ratios with or without drug (as given in Table 1) were prepared in acetate buffer (pH 4.0/ pH 5.0/pH 6.0) and dried in oven at 60°C for 6-7 h and then air dried till complete drying of hydrogel.

 

2.6. Characterization of PEC:

2.6.1. Infrared spectroscopy:

The infrared spectrum of drug, polymer and dried gel of polymer alone and combination of polymers with and without drug were recorded by KBr dispersion technique using FTIR with diffuse reflectance attachment (FTIR - 8400s, Shimadzu, Japan). Drug sample (1-2 mg) was kept and IR spectrum was recorded.

 

2.6.2. Differential Scanning Calorimetry (DSC) analysis:

The drug, polymers and dried gel of polymer alone and combination of polymers with and without drug were studied using a differential scanning calorimeter (DSC 60 Shimadzu, Japan). For the measurement, 5-10 mg samples of drug were placed in aluminium crucibles and DSC thermograms were recorded at the heating rate of 10°C/min in the range of 30°C to 300°C. Air was purged at the rate of 50 mL/min. Transition parameters were directly determined from resulting DSC thermograms.

 

3. RESULT AND DISCUSSION:

3.1. Viscosity measurement:

From the viscosity data (as given in Table 2) it is evident that viscosity of solution changes when ratio of CTN-CGN and CTN-XGM is varied. As the pH increases from pH 4 to pH 6 viscosity of CTN increases as CTN is acidic in nature, and at acidic pH the amino group of CTN is protonated and acquires positive charge (NH4+), because of this charged groups there is electric repulsion between polymer chains.6 The pKa of CTN is 6.3, therefore at pH 4 CTN was more ionized, more repulsion between polymer chains and therefore chain becomes straight which corresponds to loose network, and therefore viscosity was less at pH 4. As pH increased from pH 4 to pH 6, less ionization of molecule therefore less repulsion between polymer chains, network became more compact and so viscosity increases.

 

Fig 5.  DSC thermogram of (A) diclofenac potassium, (B) chitosan, (C) κ-carrageenan, (D) xanthan gum (E) chitosan + κ-carrageenan, (F) chitosan + κ-carrageenan + diclofenac potassium, (G) chitosan + xanthan gum, (H) chitosan + xanthan gum + diclofenac potassium

 

CGN is an anionic polymer containing acidic sulphate group with pKa 2.0. In acidic pH due to ionization, CGN acquires negative charge due to SO4- group. Because of this charged groups there was repulsion between polymer chains. At pH 6, CGN was more ionized so more repulsion between polymer chains which corresponds to relaxation of network16, therefore viscosity was less. As pH decreased from pH 6 to pH 4 ionization decrease which results in less repulsion between polymer chains, network become more compact and viscosity increases. In the presence of K+, thermoreversible gelation of CGN involves a coil-to-double helix conformational change, followed by aggregation of the ordered molecules in an infinite network.[4] M.R. Mangione, D. Giacomazza, D. Bulone, V. Martorana and P.L. San Biagio, Thermoreversible gelation of κ-previous termCarrageenan:next term relation between conformational transition and aggregation, Biophysical Chemistry 104 (2003), pp. 95–105. Article | icon_pdfPDF (215 K) | View Record in Scopus |Cited By in Scopus (20)15, 1

 

XGM is anionic polymer containing acidic –COOH group with pKa 4.  At increased pH, there was ionization and XGM acquired negative charge due to COO- group.4 Because of this charged group there was repulsion between polymer chains. At pH 6, XGM was more ionized, so more repulsion between polymer chains which corresponds to relaxation of network, therefore viscosity was less. As pH decreased from pH 6 to pH 4, as ionization decreased which results in less repulsion between polymer chains, network become more compact and viscosity increases.

 

In case of combination of CTN and CGN, there was interaction between amino group of CTN and sulphate group of CGN and PEC was formed. The formation of PEC leads to aggregation and concomitant reduction in viscosity of solution.6 In case of equal proportion of polymer, i.e. there was optimum interaction between CTN and CGN results in formation of aggregates and viscosity of solution was decreased. There is interaction between CTN and DFP so there is decrease in viscosity of CTN in its presence. CGN shows strong gel formation in presence of K+.15

 

Due to interaction between amino group of CTN and carboxylic group of XGM the formation of PECs leads to aggregation and concomitant reduction in viscosity. In case of equal proportion of polymer, i.e. there was optimum interaction between CTN and XGM results in formation of aggregates and viscosity of solution was decreased. The interaction between CTN and DFP leads to decrease in viscosity, while there is no significant change in viscosity of XGM in presence of DFP.

 

 

3.2. In vitro drug diffusion study

In diffusion study of PEC hydrogels, based on CTN-CGN and CTN-XGN matrix at different pH as shown in Fig 1, 2 and 3. There was interaction between CTN and DFP, and free drug was less available for diffusion. The solubility of drug is less at pH 4 as compare to pH 5 and pH 6. Therefore, drug release was less at pH 4 as compared to pH 5 and pH 6. Maximum release was observed at pH 6 due to less interaction of drug and polymer and more solubility of drug. CGN shows less release because of maximum viscosity of both gels. In combination CC-5 there is very less drug release due to polymer-polymer and polymer-drug interaction is maximum as polymer concentration is equal. In combination CC-4 more drug release as compare to CC-6 as concentration of CTN is more in this combination (Table-3).

 

XGM shows less drug release because of maximum viscosity of gel. In CX-5 less drug release can be observed due to maximum polymer-polymer and polymer-drug interaction as polymer concentration is equal. In combination CX-4 more drug release as compare CX-5 as concentration of CTN is more in this combination.

 

3.3. Characterization of PEC:

Infrared spectroscopy and DSC were used for examination of interaction between two oppositely charged polymers.

 

Table 3. Drug release from hydrogels of combination of polymers at different pH (mean±SD, n=3)

Formulations

Cumulative Percent drug release after 6 hrs

pH 4

pH 5

pH 6

CH-3

31.53 ± 0.59

35.69 ± 0.48

42.43 ± 0.91

CR-3

20.12 ± 0.61

22.26 ± 0.64

24.24 ± 0.99

XG-3

14.26 ± 0.46

16.12 ± 0.36

19.42 ± 0.24

CC-4

14.29 ± 0.36

15.62 ± 0.34

16.31 ± 0.64

CC-5

9.04 ± 0.56

10.37 ± 0.05

12.18 ± 0.35

CC-6

12.72 ± 0.44

14.61 ± 0.68

15.96 ± 0.77

CX-4

15.66 ± 0.88

16.21 ± 0.10

18.06 ± 0.39

CX-5

8.29 ± 0.56

10.28 ± 0.35

11.46 ± 0.57

CX-6

10.32 ± 0.16

12.29 ± 0.55

13.46 ± 0.26

 


 

Fig 6. Schemes of probable interactions between diclofenac potassium and chitosan; chitosan and κ-carrageenan.

 

 


3.3.1. Infrared spectrum:

The precipitate obtained from mixture CTN-CGN at 50:50 weight ratio was analyzed by FT-IR ((Fig 4 (E)) and compared with individual spectra of CTN and CGN. As it is seen from (Fig 4 (C)), the FT-IR spectra of CGN showed a broad absorption band at 1427 cm-1 assigned to sulphate group. The FT-IR spectra of CTN (Fig 4 (B)) showed an intense and broad absorption band at 2669 cm-1 assigned to the amine group. The FT-IR spectra of precipitate obtained from mixture of CTN and CGN (50:50) showed a new absorption band at 1569 cm-1 assigned to amine group. This absorption band is absent in the spectra of both CTN and CGN. Moreover, the intensity of absorption band assigned to amine group of CTN, and sulphate group of CGN was slightly shifted. In presence of drug DFP showed absorption band at 744 cm-1 (-C-Cl stretching), 1550 cm-1 (-NH bending), 1578 cm-1 (-COO-) showed shifting in band while the absorption band of CTN was completely vanished in CTN-DFP combination. The band assigned to -SO42 group in CTN-CGN combination shown at 613 cm-1 and 1419 cm-1 are shifted to 605 cm-1 and 1319 cm-1 respectively. A new absorption band corresponds to NH4+ present in CTN-CGN combination spectrum at 1569 cm-1 shifted to 1577 cm-1. These result shows that there is interaction between CTN-CGN-DFP. This interaction is mainly due to interaction between CTN-CGN and CTN-DFP.

 

The precipitate obtained from CTN-CGN mixture at 50:50 weight ratio was analyzed by FT-IR ((Fig 4 (F)) and compared with the spectra of CTN and XGN. As it is seen from (Fig 4 (D)), the FT-IR spectrum of XGM showed a broad absorption bands at 1724 cm-1 due to –COOCH3 and 1700 cm-1 due to –COOH.  The FT-IR spectrum of CTN showed an intense and broad absorption band at 2669 cm-1 assigned to NH4+ group. The FT-IR spectra of precipitate obtained from mixture CTN and XGN 50:50 showed a new absorption band at 1569 cm-1 assigned to –NH3 group. This absorption band is absent in individual spectra of both CTN and XGN. Moreover, the intensity of absorption band assigned to NH4+ group of CTN, and –COOCH3 and –COOH group of XGM was slightly shifted.

 


 

Fig 7. Schemes of probable interactions between diclofenac potassium and chitosan; chitosan and xanthan gum.

 


 

The IR spectrum of CTN-XGM-DFP is shown in (Fig 4 (K)). In this spectrum bands corresponds to -C-Cl stretching, -NH stretching  and -COO- of  DFP  in XGM-DFP spectrum shown in (Fig 4 (J)) at 744 cm-1, 3205 cm-1 and 1616 cm-1 are shifted to 750 cm1, 3232 cm-1 and 1562 cm-1 respectively.  The band assigned to –COO in CTN-XGM spectrum (Fig 4 (F)) at 1697 cm-1 shifted to 1703 cm-1. A new absorption band corresponds to NH4+ present in CTN-XGM combination spectrum at 1569 cm-1 shifted to 1562 cm-1.

 

3.3.2. Differential Scanning Calorimetry (DSC) analysis:

The DSC thermogram of pure CTN and CGN (Fig 5 (C) and (D) respectively). CTN shows one endothermic peak at 59.76°C of partial crystallinity; CGN shows an endothermic transition at 53.81°C of partial crystallinity, in DSC thermogram of CTN and CGN in combination ((Fig 5 (E)). The peak at 63.81°C which indicated loss of water molecule and is shifted to lower temperature than corresponding peak in CGN thermogram, which is present at 86.90°C. There was complete disappearance of peaks shown in CTN which indicates interaction between CTN and CGN.

 

The sharp endotherm having peak temperature of 284.32°C corresponds to melting of DFP ((Fig 4 (A)). An exothermic peak at 280.22°C indicated oxidation reaction between DFP and oxygen in environment.  The DSC thermogram of DFP shows three endothermic peaks as shown in Fig 5(A) the first two small endotherm observed at 51.30°C and 70.64°C corresponds to dehydration process. The DSC thermogram of CTN, CGN and DFP ((Fig 4 (F)) combination shows endothermic transition at 68.39°C corresponds to dehydration process. There are two small endothermic hubs at 68.39°C which shows loss of two water molecules. After dehydration peak there were one exothermic peak at 280.72°C, with onset and endset temperature were 276.17°C and 283.79°C respectively, which shows fusion of drug with oxygen but the endothermic peak due to melting of drug was absent. This shows interaction of drug with polymers.

 

The DSC thermogram of pure CTN and XGM (Fig 5 (B) and (D) respectively). CTN shows one endothermic peak at 59.76°C of partial crystallinity, XGM ((Fig 5 (D)) shows an endothermic transition at 58.24°C of partial crystallinity. The DSC thermogram of CTN and XGM combination shows sharp endothermic transition at 58.94°C, corresponds to average endothermic behaviour of CTN and XGM which are at 59.76°C and 58.24°C respectively. At 77.07°C shows broad peak which suggest dehydration process. At 275.61°C there was complete decomposition of XGM which shows exothermic peak which is shifted from 271.12°C in XGM due to impurity of CTN.  Onset and endset temperature are 262.36°C and 285.29°C respectively.

 

4. CONCLUSION:

This study will be useful in selecting polymer system in optimum ratio because oppositely charged at polymers at different ratio controls release of drug by forming PEC. The study of oppositely charged polymer gels will have great potential in the field of controlled drug delivery.

 

From the results obtained we confirmed the ionic interaction between oppositely charged polymers i.e. CTN-CGN, electrostatic interaction between amine group of CTN and sulphate group of CGN and the stoichiometric ratio for effective complex formation was found to be 50:50 (CTN:CGN) and also complex formation between CTN and XGM via electrostatic interaction between amine group of CTN and carboxylic group of XGM and the stoichiometric ratio for effective complex formation was found to be 50:50 (CTN:XGN). There is interaction between CTN-DFP, potassium ions of DFP caused helix-helix conformation change in CGN hydrogels. DFP loaded polyelectrolyte complex shows change in drug release as change in pH as K+ ions of DFP promoting CGN gelation. In fact, K+ induces a coil to double helix transition preceding and promoting polymer aggregation. [4] M.R. Mangione, D. Giacomazza, D. Bulone, V. Martorana and P.L. San Biagio, Thermoreversible gelation of κ-previous termCarrageenan:next term relation between conformational transition and aggregation, Biophysical Chemistry 104 (2003), pp. 95–105. Article | icon_pdfPDF (215 K) | View Record in Scopus | Cited By in Scopus (20)The final gel is almost independent on K+ concentration, because of the ordered formation of linear structure (double helix).

 

The XGM have more viscosity than other two polymers and this characteristic is maintained in combination also, CTN-XGN combination showed more viscosity than CTN-CGN. Due to polymer-polymer interaction there was decrease in viscosity of solution, on either side of this viscosity changes according to polymer present in excess amount. On addition of DFP there was abrupt increase in CGN gel due to helix- helix conformation change of CGN because of K+ ions of DFP. From the drug release study it can be concluded that due to formation of PEC, there was retardation of drug release as the drug was entrapped in polymer matrix. Rate of drug release was changed with change in pH of hydrogels. The ionic nature of drug and solubility of drug are two important factors which affects drug release. DFP release was maximum at pH 6. This effect was due to change in solubility of drugs at respective pH. It is also concluded from the study that XGM showed lowest drug release and CTN showed highest drug release.

 

From this study, it is concluded that the combination of polymers shows better results at 50-50% ratio as there is maximum interaction between polymers and drug-polymer combination. Due to PEC formation, the drug release is retarded due to formation of network of polymer complex and in which the drug in entrapped.

 

5. ACKNOWLEDGEMENT:

The authors express their gratitude to W.C.C. International, Mumbai, India for the generous gift sample of chitosan; Kachabo Gums, Navi Mumbai, India for gift sample of κ-Carrageenan; Lotus International, Mumbai, India for gift sample of diclofenac potassium.

 

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Received on 08.06.2010       Modified on 25.06.2010

Accepted on 06.07.2010      © RJPT All right reserved

Research J. Pharm. and Tech. 4 (1): January 2011; Page 113-120