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Ind. Eng. Chem. Res. 1996, 35, 3726-3729
GENERAL RESEARCH Controlled Release Formulations of Agrochemicals from Calcium Alginate El-Refaie Kenawy* and M. A. Sakran Department of Chemistry, Polymer Research Group, Faculty of Science, University of Tanta, Tanta, Egypt
The usefulness of calcium alginate as a matrix material for controlled release formulations of 1-naphthalene acetic acid as a plant growth regulator and of pentachlorophenol as a herbicide was investigated. Release rates of these active agents were measured using a UV spectrophotometer from dried gel beads. Also the use of poly(ethylene imine) (PEI) as a coating substance for the alginate beads was investigated. The results obtained from these studies indicated that release from the gel beads after coating with PEI was markedly retarded. The release rates were varied completely due to post-treatment with PEI. The release was found to be dependent on the pH of the aqueous release medium; it was slower in the acidic medium. Introduction Scientists today more than ever before are being challenged to provide new safer, more economical, and more efficient means of providing for the health and well-being of mankind. In almost every instance, the key to meeting these challenges lies in the development of evermore ingenious methods for manipulating biological factors (1). In the last few decades due to the wide use of pest-controlling and other bioactive chemicals in the agriculture and forestry, there is increasing evidence that the nation’s groundwater resources are becoming contaminated by man’s activities, including those associated with agriculture (2). Controlled release technologies have emerged as an approach with promise to solve a diversity of problems that have in common the application of some active agents in agriculture (3). Controlled release of an active agent is important not only for attaining the most effective use of the agent but also for prevention of pollution (4). Over the last few years, there have been plenty of polymeric pesticide formulations, including herbicides, growth regulators, and fertilizers. However, the major drawback with these techniques is the residual polymers that might accumulate in the soil and become harmful to the soil and plants (5, 6). Therefore, there is an attempt in our laboratory to produce systems that have a dual function of either herbicide/fertilizer (5-9) or herbicide/water conservation (10). Furthermore, the polymeric materials backbone has also been proposed to be degradable (3, 5-9). Alginates have been used as matrices for controlled release of herbicides by several workers (10-13). Alginic acid is a natural polysaccharide composed of 1,4-linked R-Lguluronic acid and β-D-mannuronic acid units. Alginic acid is a polyacid and consequently can form a gel by complexation with polyvalent cations or polyamines. In the present work, alginate was used as a matrix for the controlled release system for pentachlorophenol as a herbicide and for 1-naphthalene acetic acid as a plant growth regulator. Also, we investigated the effect of * To whom all correspondence should be addressed.
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treatment of the alginate gel beads with a cationic polymer, e.g., poly(ethylene imine), to improve the slow release characteristics. The rate of release of active agents has also been investigated under different pH of the aqueous release medium for PEI-coated alginate beads. Materials and Methods The starting material for the preparation of calcium alginate gel was sodium alginate (water soluble) from Mero Rousselot Saia Benelux (Brussels, Belgium). It was a gift from Prof. Schacht (Gent, Belgium). Pentachlorophenol solubility in water at 20 °C, 20 mg/L; readily soluble in alcohol and acetone; the alkali metal and amine salts are readily soluble in water) was supplied by Aldrich. 1-Naphthalene acetic acid (solubility in water at 20 °C, 0.042 mg/100 gm; readily soluble in alcohol and acetone; the alkali metal and amine salts are readily soluble in water) was supplied by Aldrich and was used as received. Poly(ethylene imine) (PEI) (50% water solution) was a product of the Cordova Chemical Company. UV measurements were recorded on a Shimazu recording spectrophotometer UV-240 (P/N 204-5800) (λexp, 1-naphthalene acetic acid 224 nm; pentachlorophenol 281.6 nm). Buffer Solutions. Three buffers were used (pH 4.0, 7.0, and 9.2). Buffer solutions 7.0 and 9.2 were prepared from proprietary tablets (BDH, U.K.) with the following composition for each tablet: Buffer tablet pH 7.0: 0.264 g of potassium dihydrogen orthophosphate (Analar), 0.68 g of disodium hydrogen orthophosphate dihydrate, and 0.1585 g of sodium chloride. Buffer tablet pH 9.2: 0.953 g of disodium tetraborate and 0.5 g of sodium chloride. Each tablet was dissolved in 100 mL of distilled water to give the required pH. Buffer solution pH 4 was prepared by the following procedure: 8.0 g of sodium chloride, 1.15 g of disodium hydrogen orthophosphate, 0.2 g of potassium chloride, and 0.2 g of potassium dihydrogen orthophosphate was dissolved in 1 L of distilled water. The above solution was vigorously stirred to give a solution with a pH of about 7.4, then dilute orthophosphoric acid was added dropwise with © 1996 American Chemical Society
Ind. Eng. Chem. Res., Vol. 35, No. 10, 1996 3727
vigorous stirring, and the pH of the solution was monitored with a pH meter until pH 4 was reached. Formulations of Herbicides with Alginate. The procedure of preparation of calcium alginate beads loaded with herbidies was as follows: To vigorously stirred 300 mL of 0.25 M CaCl2 solution were added dropwise 1.5% aqueous solution of sodium alginate and 1% (wt/vol) (0.4 g/200 mL) of herbicide. The resulting calcium alginate beads were allowed to cure for another 5 min in the calcium chloride solution. The beads were separated by filtration and rinsed with deionized water. The preparation of herbicide-containing formulation was done in duplicate to check the reproducibility of the formulation process. The filtrate was further used for additions of another portion of the sodium alginateherbicide suspension. Part of the gel beads was stored for gel stabilization in stoppered Elenmeyer flasks for 24 h. The liquid lost from the beads during 24 h was combined with CaCl2 solution and the rinsing water of the same batch, and then it was extracted twice with 200 mL of dichloromethane each. After removal of the dichloromethane by rotary evaporator, the residue was dissolved in 10 mL of dichloromethane and was transferred into a small flask of a known weight. The solvent was evaporated, and the herbicide residues was determined by accurate weighing. The content of the gel beads from herbicide was calculated as the difference between the amount added originally and that lost during preparation. Another procedure was used to evaluate the herbicide content of the gel beads by extracting the herbicide (6 h) from the gel beads using a solvent like carbon tetrachloride or chloroform. By evaporation of the solvent, it was possible to evaluate the herbicide content of the gel beads. Coating of Herbicide-Containing Gel Beads with Poly(ethylene imine). The procedure as for coating of 1-naphthalene acetic acid containing gel beads was typical as follows: The gel beads were transferred to 100 mL of a 10% aqueous solution of poly(ethylene imine) and stirred for 1 h. Then the beads were separated, washed with deionized water, and air dried. Release Experiments. Release rates for the formulations in water solution with different pH were conducted at room temperature as follows: Dried beads (200 mg) were placed into a flask designed in our laboratory for controlled release (7) containing 100 mL of an aqueous buffer solution. The flask was mechanically shaken at a room temperature of 22 °C. At regular intervals, samples were taken from the release medium for measurements of herbicide released by UV spectrophotometry using calibration curves for different substances. Samples were taken during the first day at intervals of several hours; the later intervals were of 1 to several days. After each sampling, except those during the first day, all of the release medium was refreshed to minimize saturation effects and to simulate field application. Formation of the Gel Beads. Aliginic acid sodium salt was used as a starting material. When added to a stirred solution of calcium chloride, it gives gel beads immediately with an average diameter of 4 mm. In presence of the herbicide, the gel beads trap herbicide inside the beads; therefore, it could be a controlling device for the herbicides. The simplified structure of PEI-coated aliginate beads containing active agents is schematically represented in Figure 1. Coating of Gel Beads with PEI. Upon treatment of the gel beads with PEI solution, they shrink to about
Figure 1. Schematic presentation of the structure of calcium alginate beads coated with PEI and containing active ingredient A.
25-30% of their original diameter (13). The beads were coated by PEI by immersing the beads containing the herbicide in a PEI-water solution for 1 h to form surface-coated gels that might work as another barrier to control the release of the active agents. Release Studies. The release of 1-naphthalene acetic acid and pentachlorophenol was carried out at 22 °C in reconstituted freshwater at pH 4, 7, and 9.2. The amount of herbicide released within the time was monitored by UV analysis. Investigation of the effect of PEI coating and pH of the release medium on the release rates has been carried out. Results and Discussion Release Characteristics of the System. The alginate formulation described in this work was classified as a physical method for controlling the release of the bioactive agent. All the physical methods are in one way or another controlled by the diffusion of the active agent through a polymer barrier. In the case of PEIcoated systems, the release of an active agent is achieved through a combination of diffusion and erosion. Characterization of Loaded Beads. Alginate gel beads loading was determined by two methods. First, by calculating the weight loss of herbicide during the preparation of the alginate formulations as described in the experimental section. Second, by extracting a well-known amount of dried beads (100 mg) using 50 mL of chloroform or carbon tetrachloride, the extraction was continued for 6 h. After evaporation of the solvent, it was possible to determine the herbicide content of the gel beads. Effect of PEI Coating on Release Rates. Controlled release formulations prepared by utilization of biopolymers are of special interest because of the possible biological degradation of matrices when the duration of action has finished, in addition to the relatively low cost of raw materials. The use of alginic acid or its sodium salt as a starting material for the preparation of the slow release of herbicide formulations has been of special interest due to the reasons mentioned above (2, 11, 12). Poly(ethylene imine) (PEI) was selected because it has been reported that the treatment of calcium alginate with cationic polymers such as PEI leads to the formation of surface-coated gels that have superior stability properties (13, 14, 16).
3728 Ind. Eng. Chem. Res., Vol. 35, No. 10, 1996
Figure 4. Effect of PH of the medium on the release of 1-naphthalene acetic acid from calcium alginate beads. Figure 2. Release of 1-naphthalene acetic acid from calcium alginate beads without and with coating with PEI in buffer solution.
Effect of pH of the Release Medium on the Release Rates. Alginate beads containing 1-naphthalene acetic acid coated with PEI were selected to determine the effect of the pH of the release medium on the release rates. As shown in Figure 4, the 1-naphthalene acetic acid was released from the calcium alginate gel beads with widely varying rates. The release rate was increased with increasing pH of the release medium. Similar results were reported by Suhaila and Salleh (16). They concluded that in the pH region of 3-6 the shrinkage increased with increasing pH. A similar trend was shown by Schacht et al. (15) for dichlobenil (2,6-dichlorobenzonitrile) alginate formulations. It was expected that, in this system in acidic medium, the alginic carboxylate groups are protonated, forming more hydrophobic alginic acid. This might explain the slower release rate observed for the PEIcoated alginate system in an aqueous pH of 4. Conclusions
Figure 3. Release of pentachlorophenol from calcium alginate beads without and with coating with PEI.
It was generally noticed that the swelling of PEIcoated samples in the release medium was much less than the dried calcium alginate beads. After treatment of the beads with PEI, they shrink to about 25-30% of their original diameter with the expulsion of water, which is accompanied by a significant loss of pesticide. Similar results were reported by Schacht et al. (15). As illustrated in Figure 2 for the release of 1-naphthalene acetic acid, it was found that for the uncoated samples 75% of the herbicide content was released within the first 8 days while the percent of release was within about 38 days from the PEI-coated alginated beads. The same behavior was observed for the release of pentachlorophenol from the alginate beads (Figure 3). So, 75% of pentachlorophenol was released after the fifth day while the percent of release was observed after 20 days from the PEI-coated alginate. In general, post-treatment of calcium alginate beads containing herbicide resulted in a remarkable decrease of the release rates, as illustrated in Figures 2 and 3. This is in good agreement with the results reported by Schacht et al. (15) for a series of pesticide-containing calcium alginate beads.
The use of calcium alginate as a physical device for controlling the release of bioactive agents was investigated. The use of PEI to prepare surface-coated beads was also investigated and showed that the pre-treatment of beads with PEI could prolong the duration of release. The pH of the medium was found to be an important parameter, and slower release rates were in pH 4. Finally, it is anticipated that the naturally occurring polymer will degrade biologically when the duration of action has finished. Also, these systems have an advantage of relatively low cost of the raw materials. Acknowledgment We would like to thank Prof. E. Schacht at the University of Gent (Belgium) for providing the alginate and for his invaluable advice and important discussions. Literature Cited (1) Cowsar, D. R. In Controlled Release of Biologically Active Agents; Tanquary, A. C., Lacey, R. E., Eds.; Plenum Press: New York, 1974; p 1. (2) Pepperman, A. B.; Kuan, J. W.; McCombs, C. J. Controlled Release 1991, 17, 105-112. (3) Kenawy, E. R. Agricultural Polymers with a Combined Herbicide/Fertilizer Function-IV. J. Mater. Sci. 1996, in press.
Ind. Eng. Chem. Res., Vol. 35, No. 10, 1996 3729 (4) Lu, S. M.; Lee, S. F. J. Controlled Release 1992, 18, 171180. (5) Kenawy, E. R.; Sherrington, D. C.; Akelah, A. Eur. Polym. J. 1992, 28, 841. (6) Kenawy, E. R. Recent advances in controlled release of pesticide. Submitted to Trends Polym. Sci. (7) Akelah, A.; Kenawy, E. R.; Sherrington, D. C. Eur. Polym. J. 1992, 28 (5), 453-463. (8) Akelah, A.; Kenawy, E. R.; Sherrington, D. C. Eur. Polym. J. 1992, 28, 615-621. (9) Akelah, A.; Kenawy, E. R.; Sherrington, D. C. Eur. Polym. J. 1993, 29, 1041-1045. (10) Issa, R.; Akelah, A.; Rehab, A.; Solaro, R.; Chiellini, E. J. Controlled Release 1990, 13, 1. (11) Pepperman, A. B.; Kuan, J. J. Controlled Release 1993, 26, 21-30. (12) Pfister, G.; Bahadir, M.; Korte, F. J. Controlled Release 1986, 3, 229-233.
(13) Veliky, I. A.; William, R. E. Biotechnol. Lett. 1981, 3, 275. (14) Lim, F. U.S. Patent 4,352,883, 1982. (15) Schacht, E.; Vandichel, J. C.; Proceedings of an International Symposium on Changing Prespectives in Agrochemicals, Heuherberg, Nov 24-27, 1987; International Atomic Energy Agency: Vienna, 1988. (16) Suhaila, M.; Salleh, A. B. Biotechnol. Lett. 1982, 49, 611.
Received for review July 19, 1995 Accepted May 24, 1996X IE950448M
X Abstract published in Advance ACS Abstracts, September 1, 1996.
