Enzyme Capsules Research Articles

Encapsulation of enzymes by radiation technique

A new preparative technique for the encapsulation of enzymes by radiation polymerization was studied using cellulase, 2-hydroxyethyl methacrylate, and tetraethylene-glycol diacrylate. The enzyme activity of the immobilized enzyme capsules varied with the thickness of the membrane and with the size of the capsule; optimum size and thickness giving high enzyme activity were 0.5 – 2 mm and 50 – 200 μm, respectively. The durability of the capsules was examined by continmuous enzyme reaction.

Comparison with Enteric Coated Films of Digestive Enzyme Capsules

The enteric coated granules contained in 10 kinds of commercial digestive enzyme capsules were examined for change with time of resistance in pH 5.0 test solution and dissolution in pH 7.0 solution. Changes of resistivity with time were recognized in nine samples. Furthermore, the enteric coated films of two samples were weakened with ime and were liable to rapid dissolution, whereas those of two other samples were hardened and interfered with enzyme dissolution. Consequently, it was suggested that one must be more careful about the change of the enteric coated films of digestive enzyme preparations with time than that of their activity.

Change with Time in Activity and Dissolution of Digestive Enzymes in Capsule

Six brands of multiple digestive enzyme capsules were tested for their stability of weight, disintegration of capsules, enzyme activity and dissolution in the solutions of pH 6.5, 5.0 3.0, and the 2nd fluid of J. P. IX after storage in press-through pack (PTP) at room temperature for one year. After storage, properties of some preparations were degraded. When stored in simple packs prepared by the manufacturers, the preparations maintained better stability than the storage in PTP, though slightly degraded in quality.AC and PT were tested for the change with time in their activity and dissolution through the storage at 30°, 80% RH, and at 35°, 80% RH in and out of PTP. At 30°, their enzyme activity seemed to be stable for 4 weeks, though the color and odor of the content of capsules increased gradually. Acid resistance of enteric coating of PT, which was initially excellent, was gradually lowered. After storage for 6 weeks at 35°, AC and PT changed solubility of capsules, and their odor became practically intolerable.

Qualitative Comparison between Digestive Enzyme Preparations

Quality of 3 multiple digestive enzyme capsules (PA, ST, HO) were compared in terms of their digestive activities in the digestive organs where the enzymes are dissolved, as well as of weight variations and protease potency variations (20 capsules for each sample). In pharmaceutical quality, PA was most excellent, followed by ST and HO, in that order, but amilase of PA must be improved. ST was noted for its long-sustained digestive activity. HO had weak digestive activity except for acid protease activity, and its dose should he 2-4 times as high as that of PA or

Weight Variation of Test Components of Multiple Digestive Enzyme Capsules and Relationship between Their Weight and Activity

Pharmaceutical properties of 4 kinds (A to D) of multiple digestive enzyme capsules were investigated. Weight variations of the capsules as a whole and those of gastricsoluble and enteric-soluble parts of each capsule were determined. Coefficient of variation (CV) of capsule was less than 2 % for all capsules. However, CV's of gastric-soluble part and that of enteric-soluble one for each capsule were larger than that of the whole capsule (range 2-8%); coefficients of variation of both parts of sample A were less than 4% and those of sample D were 7-8%. For 3 samples except sample A, reciprocal correlation was observed between weights of gastric-soluble part and of enteric-soluble one. Further, relationship between weight of enteric-soluble part and the activity of alkaline protease was good in any capsule, with the favorable correlation coefficient 0.9. From these results, it is suggested that weight variation should be reduced not only of whole capsule but of respective contents.

Identification of Coating Materials for Enteric Coated Preparations

Enteric coating substances were tested in terms of disintegration time of the preparations. The samples used are 8 brands of multiple digestive enzyme capsules containing enteric coated granules and 5 of enteric coated granules (2 anti-inflammatory enzyme preparations and 1 each preparation of an antipyretic, kallidinogenase and ATP). The dissolution test was also conducted on the digestive enzyme preparations. Although all the samples passed the disintegration test of J. P. IX, the disintegration time of all the samples delayed when pH of the test solution was less than 6.0. After detailed observation, the samples were classified into two groups: group 1 in which disintegration time delayed at 5.25 and stopped at pH 5.0, and group 2 in which the time delayed at pH 5.5 and stopped at pH 5.25. The delayings were also found in the dissolution profiles of active ingredients from the sample preparations. In the analysis of the enteric coating substances by infrared spectra, the substances in group 1 were identified with hydroxypropyl methyl cellulose phthalate and those in group 2 with cellulose acetate phthalate. It is concluded that enteric coating substances used in pharmaceutical preparations are identified by the disintegration time and infrared spectra.

Dissolution and Stability of Enzymes Contained in Multiple Digestive Enzyme Capsules (2)

Digestive activity, dissolution and stability of enzyme ingredients were compared among 4 commercial products (SV, EX, BE and FE) of multiple digestive enzyme Capsules. 1) Amylase: Gastric-soluble pellets of FE showed a strong and stable digestive activity in broad pH range, but enteric-soluble pellets had a weak activity. Gastric-and enteric-soluble pellets of 3 other products showed an equal digestive activity, but alkaline amylase activity of SV and EX became inactive in acidic solution. 2) Protease: Gastric-soluble pellets of BE and enteric-soluble pellets of FE had weaker digestive activity, and all other products had an equally strong digestive activity and stability. 3) Lipase: Gastric-soluble pellets of FE showed a strong and stable activity in broad acidic area, and digestive activity of entericsoluble pellets was rated in the order of EX>SV=BE>FE. Stability of lipase of 4 products lowered in proportion to increase in pH value of alkaline solution, but the strong lipase activity of the 4 products persisted for a long time in a weak acidic solution. 4) Cellulose: Cellulose, contained in only gastric-soluble pellets of 4 products, showed an equal digestive activity and stability, except for strong digestive activity of BE and excellent stability of FE. 5) Dissolution of enzymes contained in enteric coated pellets: FE showed excellent dissolution and BE had less dissolution of some pellets. Dissolution of enzymes from some enteric coated pellets of EX was noted in acidic solution. The above findings indicated that BE and EX contain heterogeneous pellets.

Activities and Dissolution of Enzymes in Commercial Multiple Digestive Enzyme Capsules

Three brands of commercial multiple digestive enzyme capsules (EX, RZ and FT) were tested for their digestive enzyme activities and dissolution of enzymes in the solution of pH 3.0, 5.0, 6.5 and 7.5. Further, digestive enzyme activities and weight variations of the products in three different lot numbers were compared with each other. EX had strong activities of lipase and protease (pH 7.0), but acid-resistance of enteric coated granules was relatively weak. Enzyme activities of RZ and FT were not so strong, but their enteric coated granules showed satisfactory acid-resistance, being dissolved in the solution with pH 6.5 but not in the solution with pH 5.0. Generally, inter-lot differences of enzyme activities were found to be comparatively small.

Dissolution and Stability of Enzymes Contained in Multiple Digestive Enzyme Capsules

Digestive activity, dissolution and stability of enzyme ingredients were compared among three commercial products (A, B and C) of multiple digestive enzyme capsules containing gastric active ingredients and enteric coated granules, respectively. Product A provides mainly gastric active enzymes with strong amylase activity. Dissolution of enzymes from enteric coated granules was observed in the acidic solution, but the rate was faster in the alkaline solution. Product B provides enzymes which maintain their activity throughout the gastrointerstinal tract and has strong protease activity. Dissolution patterns of enzymes were similar to product A. Product C provides mainly enteric active enzymes with less cellulase activity. Lipase compounded in gastric active ingredients should be transferred to enteric coated granules. Enteric coated enzyme ingredients were scarcely dissolved in the acidic solution, and the dissolution rate was lower in the alkaline solution. Enzymatic activity of the three products, except lipase, were stable.

A general model for the packed bed encapsulated enzyme reactor

AbstractA model has been developed for the performance of a packed bed encapsulated enzyme reactor which includes all the resistances controlling the rate of reaction plus the effect of axial dispersion of the bulk liquid. The method of solution to the problem is based on the application of the orthogonal collocation method to both the enzyme capsule and the bulk liquid, thereby reducing the problem into one of solving a number of simultaneous first order ordinary differential equations.