European Journal of Pharmaceutics and Biopharmaceutics
Research paperEnhanced enteric properties and stability of shellac films through composite salts formation
Abstract
The objective of this study was to improve the properties of shellac by composite salts formation. The shellac samples were prepared in various salt forms by dissolving them with 2-amino-2-methyl-1-propanol (AMP) and ammonium hydroxide (AMN) at various ratios of AMP:AMN. The results demonstrated that aqueous solubility of the shellac salts was improved as the ratio of AMP:AMN increased. The absorbance ratio of the FTIR peaks assigned to C
O stretching of carboxylate and carboxylic acid (ABS1556/ABS1716) was increased with the increase of the AMP fraction, suggesting that the solubility enhancement was due to more ionization of AMP salts. Moisture adsorption studies indicated that shellac salts were more hygroscopic as AMP content increased. After storage at 40 °C, 75% RH, the acid value and insoluble solid of AMP salts were relatively constant even after storage of up to 180 days, suggesting that AMP should protect polymerization. The ABS1556/ABS1716 values of the shellac salts were rapidly decreased after storage, especially for those consisting of a high percentage of AMN. Thus, AMP should bind much tighter at the carboxylate binding site as compared with AMN, resulting in more solubility and stability. In conclusion, optimized shellac properties could be easily accomplished by composite salts formation.
Introduction
Shellac is a purified resinous secretion of lac insects, Laccifer Lacca, which are mostly cultivated in host trees in India and Thailand. The shellac is widely used in the food industry, to some extent still in the pharmaceutical industry and a market of growing interest in nutritional supplement, health supplement, and nutriceuticals [1]. In the pharmaceutical industry, shellac has been used for moisture protection and glossing, while the use for enteric coating of pharmaceutical products has greatly declined [2]. Severe problems associated with enteric properties are low solubility at the pH of the intestine and lesser stability of shellac as compared to synthetic and semi-synthetic enteric polymers, e.g., polyacrylates and cellulose derivatives [3]. The shellac possesses a high pKa between 6.9 and 7.5 and begins to dissolve at pH 7.0. However, the pH in the proximal region of the small intestine is between 3.8 and 6.9 and the failure of shellac coated tablets or capsules to disintegrate at these pH media is still a major problem [2], [4]. During many years, several attempts have been made to clarify the problem. Pearnchob et al. developed a faster disintegrated shellac coated capsule by adding organic acids, e.g., sorbic acid and benzoic acid. The addition of organic acids decreased the disintegration time in phosphate buffer (pH 6.8) while the behavior in 0.1 N hydrochloric acid was unchanged [5]. The hydrolysis process was also used as a method for improving the solubility of shellac. The partially hydrolyzed shellac showed greater solubility and dissolution, especially at pH 7.0 and lower [6]. However, a stabilization method for shellac is not completely developed.
As shown in Fig. 1, shellac is composed of polyesters and single esters that contain a large amount of hydroxyl and carboxylic acid. The polymerization can occur by the esterification among the functional groups and was the cause of instability [7]. Since the polymerization occurred via a carboxyl group, the protection at the carboxylic acid should be a possible means for improving the stability of shellac. Specht et al. demonstrated that application of shellac from an aqueous solution of alkali salts showed better stability than the application from ethanolic solution [8]. Similar results were observed by our group. The ammonium salt of shellac demonstrated better stability and solubility, as compared with shellac in free acid form [9]. However, the stability of ammonium salts was decreased after storage at stress condition for a long period, especially under the test condition of a tropical zone (40 °C, 75% RH) for more than 3 months. The loss of ammonium ion from the carboxylic group might be a possible explanation that still needed to be investigated. In addition, another salt forming agent, especially one more tightly bound to the carboxylic acid, should be examined and the mechanism of the stabilization process should be further clarified.
The aim of the present study was to evaluate the effect of salt forming agents on enteric properties and stability of shellac. Ammonium hydroxide (AMN), 2-amino-2-methyl-1-propanol (AMP) and the combination of both bases were selected as the salt forming agents in this study. The shellac samples, in acid form and various salt forms, were prepared and comparatively evaluated.
Section snippets
Materials
Shellac was purchased from Thananchai Part., Ltd. (Bangkok, Thailand). Other reagents used were of analytical grade and used as received.
Preparation of partially hydrolyzed shellac
Partially hydrolyzed shellac was prepared by a previously described method [6]. Shellac (200 g) was dissolved in 2% w/w sodium hydroxide solution (1800 g) and kept at 30 ± 1 °C for 8 min. The mixtures were then immediately neutralized with 2 N sulfuric acid, washed with excess water, and dried. The partially hydrolyzed shellac was kept in the refrigerator prior to
Physicochemical properties
The effects of salt forming agents (bases) on physicochemical properties, including solubility, acid value and insoluble solid, were determined. Shellac salts with various ratios of AMP:AMN at 0:100, 20:80, 40:60, 60:40, 80:20, and 100:0 were compared with the free acid form.
Fig. 2 demonstrates the percentage dissolved (bar chart) and dissolving time (line chart) of various shellac forms after immersion in simulated gastric fluid for 2 h and transferring to buffer at various pH values for 3 h.
Conclusion
The improved enteric properties of the shellac films were easily achieved by AMP:AMN composite salts formation. The main disadvantages of AMN salt, including less solubility and less stability, were compensated for by combination with AMP salt, whereas the main disadvantages of AMP, including high hygroscopicity and low film strength, were counterbalanced by combination with AMN salt. The optimum ratio of AMP:AMN should be in the range of 40:60–80:20 with regard to solubility, hygroscopicity,
Acknowledgements
This work was supported by the Thailand Research Fund, the Commission on Higher Education, the Research Institute of Silpakorn University and the Faculty of Pharmacy, Silpakorn University. The authors also would like to thank Mr. Vacharapon Rangnim for his technical assistance.
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