PHARMA SCIENCE MONITOR

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1 PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES SYNTHESIS, CHARACTERIZATION AND ELECTRICAL STIMULUS SENSITIVE BEHAVIOR OF psy-cl-poly(aa) HYDROGEL Deepak Prashar * 1, Shalini Sharma 1, Sukhbir Lal Khokra 2 1 Department of Pharmaceutics, Manav Bharti University, Solan (H.P.), India 2 Department of Pharmaceutical Chemistry, Manav Bharti University, Solan (H.P.), India ABSTRACT Many natural gums are currently available as a backbone for the formation of polymers as a drug delivery carrier. The purpose of this study is to search for effective and economical material that can be used as an effective stimulus sensitive drug delivery device. Psyllium based polymer was synthesized using free radical polymerization mechanism. The synthesized polymer was further characterized using scanning electron microscopy (SEM). Psy-cl-poly(AA) was studied for its electrical stimulus sensitive responsive behavior using 5V AC/DC current source at 37 0 C using artificial biological fluid. Keywords: Psyllium, crosslinking, polymer, stimulus sensitive, drug carrier. INTRODUCTION Hydrogels are the three dimensional crosslinked polymer networks which can absorb water up to thousand folds of their dry volume while maintaining the three dimensional network structures. This ability to absorb water is mainly due to the presence of ionic functional groups [1]. Based on the response of hydrogel to the exterior stimulation, the hydrogel can be divided into traditional hydrogel and intelligent/smart hydrogel. The intelligent hydrogel can perceive external stimulations such as temperature, electric field, magnetic field, light, ph and ion strength [2-4] and show significant expansions in the response process. This characteristic can be utilized to apply the intelligent hydrogel into the medicine controlled release, stimulant drug delivery, memory component switch, artificial muscle and many domains [5-7]. Kim et al. [8] reported the bending behaviors of poly (acrylic acid)/poly acrylonitrile semi IPN hydrogels under various voltage conditions. They reported that as the applied voltage increases, the bending speed increases and further the deformation of the IPN hydrogels was reversible when the applied voltage was turned on and off. Osada et al. [9] reported the electrically activated artificial muscle system which contracted by IC Value

2 the electrical stimulus under isothermal conditions. Zhang et al. [10] identified the stimuliresponse of hydrophilic-hydrophobic semi-ipn hydrogels under DC electric field. Wong et al. [11] concluded through their studies that electrically conducting polymers can noninvasively control the shape and growth of mammalian cells. Giaever et al. [12] monitored the behavior of fibroblast in tissue culture under an applied electric field. In this research paper, synthesis and characterization of psyllium-acrylic acid based hydrogels using KPS-ascorbic acid and glutaraldehyde as an initiator-crosslinker via free radical polymerization technique. The electrical stimulus response of the candidate polymer was evaluated using AC/DC current source by using artificial biological fluid as a solvent medium. MATERIAL AND METHODS Psyllium (Sidhpur Sat-Isabgol Factory, India) and ascorbic acid-potassium persulphate (SD Fine Chemicals Pvt. Ltd.) were used as backbone and initiator, respectively. Glutaraldehyde (MERCK) and acrylic acid (MERCK) were used as crosslinker and monomer, respectively. Oral Electrolyte Powder (Cipla pharmaceutical Ltd.) was used as received. Instrumental Analysis Scanning Electron Micrographs (SEM) of the candidate polymers were taken on LEO-435VF, LEO Electron Microscopy Ltd. Synthesis of superabsorbent 1.0 g of Psyllium was taken in a reaction flask containing 25ml of distilled water. To the reaction mixture 0.5mol L -1 of acrylic acid was added followed by the addition of ascorbic acid-kps in 1:1.25 molar ratios as an initiator system and 0.42mol L -1 of glutaraldehyde as a crosslinker. The reaction was carried out at ph 7.0 for 110min at 45 O C. At the end of the reaction the homopolymer was removed on washing with hot water and the gel obtained was allowed to stand for about hours undisturbed for gelling process to take place. The product obtained was dried in the oven at 60 O C till a constant weight was obtained. The percentage grafting and percentage swelling was calculated as per the following equations 1 and 2: IC Value

3 F W - I W % G = (1) I W Where Iw = initial weight of the material taken; F w = final weight of the material obtained F sp I up % S = (2) I up Where I up = initial weight of unswelled polymer; F sp = final weight of swelled polymer Electrical Stimulus Sensitive Studies Apparatus used for the electrical stimulus sensitive studies is shown in the Fig. 1. The system consists of an inner compartment [20.5cm(l) 15cm(b) 10cm(h)], two copper electrodes [8cm(l) 5.3cm(b) 0.2cm(h)], a thermostat, thermometer, and an outer compartment [24.5cm(l) 19cm(b) 12cm(h)] acting as a closed system. Distance between two copper electrodes was about 15.5cm. Preoptimised and dried hydrogel having weight (Wd) was immersed in distilled water/ artificial biological fluid at 37 o C and 5V AC/DC source. On the application of electrical stimulus polymer shows swelling behavior and was weighed after a regular time interval. Percentage swelling (Ps) was calculated by the formula: Ps = Ws Wd 100 Wd Where W s and W d are weights of swollen polymer and dry polymer respectively. IC Value

4 Figure 1 Apparatus for AC/DC stimuli studies Preparation of artificial biological fluid Artificial biological fluid was prepared in the laboratory using electrolytic powder and distilled water (DW). 25gms of electrolytic powder was dissolved in per 1000ml of distilled water to obtain the artificial biological fluid of 25000ppm. RESULT AND DISCUSSION Characterization SEM In order to have the conducting impact, the samples were gold plated and the scanning was synchronized with microscopic beam so as to maintain the small size over a large distance relative to the specimen. A remarkable three dimensional appearance with high resolution was obtained in case of crosslinked product. SEM images clearly exhibited the differences in the surface morphology of the psyllium and Psy-cl-poly(AA) which were brought about through copolymerization and crosslinking (Fig 2a-b). IC Value

5 Figure 2 SEM of (a) Psyllium; (b) Psy-cl-poly(AA) ELECTRICAL STIMULUS SENSITIVE STUDIES USING DC / AC SOURCE Effect of AC source on percentage swelling of bio-polymer in artificial biological fluid The electrical stimulus studies were carried out at a time interval of 4 hours using AC current source at 37 0 C. Swelling behavior of candidate polymer was estimated using artificial biological fluid. Maximum swelling found in artificial biological fluid is 524% (Fig 3). Initially a rapid swelling was reported in the candidate polymer which might be because of the fact that the solvent system on electrolysis dissociate into ions which easily made entrance in the gel network and swelling is observed. But after reaching the optimum value the swelling rate becomes constant. This might be because of the fact that when current is applied for longer duration of time the dissociated ions play screening role between other ions present in the network and do not allow them to move out of the gel network, thereby, giving a constant percentage swelling. IC Value

6 Figure 3 Percentage swelling of candidate polymer under AC source Effect of DC source on percentage swelling of bio-polymer in artificial biological fluid Figure 4 shows the swelling behavior of candidate polymer under the influence of DC current source (5V) at 37 0 C using artificial biological fluid as a solvent system. It was observed that percentage swelling increases rapidly with time under the influence of DC source. Maximum swelling found in artificial biological fluid is 448%. It might be due to the fact that under the influence of DC source electrolysis takes place with the generation of H + and OH - ions, which exerted ion screening effect further, electrostatic repulsions took place and resulted in the increase rate of swelling of crosslinked system. Moreover, under the influence of DC source, maximum swelling in artificial biological fluid is less in comparison to AC source. This might be because of the fact that under the influence of DC source the polymer shows shrinking behavior resulting in lesser swelling. IC Value

7 Figure 4 Percentage swelling of candidate polymer under DC source CONCLUSION The results suggested that, the synthesized polymer shows excellent electrical responsive behavior under both AC/DC sources. Moreover, the polymer shows better and effected results at body temperature (37 0 C) and AC source mimicking the conduction pattern in human body. The studies indicates that the Psy-cl-poly(AA) may be used for stimulus sensitive drug delivery system as an effective and alternate drug carrier in comparison to synthetic backbone based polymers. REFERENCES 1. Buchholz FL and Graham AT: Modern superabsorbent polymer technology. Wiley. New York: Mahdavinia GR, Pourjavadi A, Hosseinzadeh H and Zohuriaan MJ: Superabsorbent hydrogels from poly(acrylic acid-co-acrylamide) grafted chitosan with salt- and ph-responsiveness properties. European Polymer Journal 2004; 40: Hennink WE and Nostrum CF: Novel crosslinking methods to design hydrogels. Advance Drug Delivery Review 2002; 54: Qui Y and Park K: Environment-sensitive hydrogels for drug delivery. Advance Drug Delivery Review 2001; 53: IC Value

8 5. Hamlem RP, Kent CE and Shafer SN: Electrolytically Activated Contractile Polymers. Nature 1965; 206: Hirokawa Y, Tanaka T and Sato E: Phase Transition of Positively Ionized Gels. Macromolecules 1985; 18: Kuhn W, Hargitay B, Katchalsky A and Eisenberg H: Reversible Dilatation and Contraction by Changing the State of Ionization of High-polymer Acid Networks. Nature 1950; 165: Kim SJ, Lee KJ and Kim SI: Electrostimulus responsive behavior of poly(acrylic acid)/polyacrylonitrile semi-interpenetrating polymer network hydrogels. Journal of Applied Polymer Science 2004; 92: Osada Y and Hasebe M: Electrically activated mechanochemical devices using polyelectrolyte gels. Chemical Letter 1985; 14: Zhang J and Yang Y: Stimuli-Response of Hydrophilic-Hydrophobic Semi-IPN Hydrogels under DC Electric Field. Acta Polymerica Sinica 2002; 1(1): Wong JY, Langer R and Ingber DE: Electrically conducting polymers can noninvasively control the shape and growth of mammalian cells. Proceeding of National Academy of Science 1994; 91(8): Giaever I, Keese CR.: Monitoring fibroblast behavior in tissue culture with an applied electric field. Proceeding of National Academy of Science 1984; 81(12): For Correspondence: Deepak Prashar prashardeepak99@ymail.com IC Value