Method Of Sugar Coating Tablets

Abstract

A sugar-coated tablet characterized by high stability is prepared by a simple and commercially feasible procedure. The tablet is prepared by applying to the tablet core an aqueous sugar solution containing calcium lactate.

Description

DETAILED EXPLANATION OF THE INVENTION:

The present invention relates to a method of coating tablets, or the like, by applying thereto a sugar coating composition comprising an aqueous sugar solution containing calcium lactate.

Sugar-coated tablets are widely used owing to the remarkable excellency in taste, odor and appearance as compared with tablet cores and such tablets have the effect of preventing medicaments, and the like, which are present in the tablets from being decomposed by air or moisture. On the other hand, such tablets are characterized by the following shortcomings:

A. Because the various steps such as sealing, subcoating, rounding, smoothing, coloring, finishing etc., for preparing the sugar-coated tablets must be performed generally, manually, such an involved procedure requires an extended period of time, i.e., about 1 week to produce such sugar-coated tablets. Further, it is extremely difficult to produce such tablets automatically.

B. In order to obtain sugar-coated tablets of high strength, it is necessary to form a coating layer having sufficient thickness so that its weight is almost equal to that of the tablet core and in order to form such a coating layer, the number of the coating operations must be increased thereby prolonging the time required to produce the coating. Furthermore, by using such a procedure, it is difficult to obtain sugar-coated tablets characterized by uniform weight.

C. Conventional sugar-coated tablets are not readily disintegrated in digestive organs and in particular, the disintegration time increases with the passage of time.

D. The sugar-coated tablets tend to crack during storage.

E. The color of the sugar-coated tablets tends to fade by exposure to temperature, humidity, light, etc. and

F. Sugar-coated tablets are subject to damage by impact.

Various attempts have been made to overcome the aforesaid difficulties and objectionable features characterizing sugar-coated tablets obtained by prior art procedures. For example, one method has been described for adding calcium sulfate in a sub-coating procedure and this is described in Japanese Patent Publication No. 17,537/1964. Another method involves adding fine crystals of cellulose to a sucrose-containing aqueous solution and this is described in Japanese Patent Publication No. 26,918/1965. However, while these methods did increase the strength of the sugar-coated tablets and prevented the formation of cracks to some extent, the disintegration time of the resulting tablets was unduly prolonged.

Moreover, there is also known a high-speed sugar coating method in which the period of time required for coating is reduced and this procedure involves the use of a mono-liquid type coating composition prepared by adding a high molecular weight compound such as polyethylene glycol to a sucrose solution. This method is described in U.S. Pat. No. 3,331,696 but this procedure is also objectionable in that the appearance of the resulting tablet is objectionable and also the tablets prepared by this method are subject to cracks and are easily damaged.

There is a known method for avoiding the production, manually, of sugar-coated tablets, thereby overcoming the objection set forth in paragraph (a) supra, formed by spraying onto tablet cores, a coating composition of a single component at pressure of 800 - 1,500 pounds per square inch thereby avoiding a pre-treatment which calls for specific skill and manual handling (see, e.g., U.S. Pat. No. 3,361,631). This method may achieve the purpose of saving labor but is still objectionable in that the sugar-coated tablets prepared by this method are not sufficient in strength and therefore are liable to be damaged. Furthermore, when the medicaments or other active materials, and the like, present in the tablets are sensitive to moisture, such a method cannot overcome the problems that are encountered when the sugar-coated tablets are stored for a long period of time under a high-humidity condition as the medicaments or other active material, and the like, which are present in the tablets are liable to transude (resulting in the loss of its commercial value) and also, the tablets are liable to decompose.

Other methods are known to produce sugar-coated tablets but they are also undesirable because while some of the objectionable features referred to above may be eliminated, other objectionable features must still be dealt with.

The main point of this invention is to make it possible to substantially reduce the production time and thereby reduce labor costs involved in the production of sugar-coated tablets by using a coating solution having a single component without forming sugar coatings involving the successive use of several kinds of coating solutions, each of such solutions having a different composition.

Another object of this invention is to provide sugar-coated tablets characterized by (1) an acceptable disintegration time, (2) freedom from cracks, and substantially stable on prolonged storage that is, resistant to surrounding or environment conditions such as temperature, moisture, and light, the aforesaid characteristics being far superior to conventional sugar-coated tablets.

A further object of this invention is to make it possible to apply directly, a sugar coating composition, to tablet cores, without requiring such pre-treatments as sealing, and the like, to the tablet cores, prior to the application of sugar coating to the tablet cores.

Following considerable investigation, it has been discovered, quite surprisingly and unexpectedly, that when a coating solution containing sugar and calcium lactate is used for the preparation of sugar-coated tablets, not only is the objectionable feature described in paragraph (a) supra, is avoided but also the objectionable features described in paragraphs (b) - (f) supra, are also obviated.

The present invention is based on the novel and highly surprising and unexpected discovery that when a sugar syrup containing calcium lactate is allowed to stand, fine crystals of sugar are precipitated and the whole syrup is uniformly solidified.

It is known that when calcium lactate is added to an aqueous sugar solution, the viscosity of the solution increases or the solution becomes jelly-like (see, Kirk-Othmer, "Encyclopedia of Chem. Tech.;" 12, 2nd Ed., edited by A. Standen et al., Interscience Publishers Inc., N.Y. (1967), page 183; Chemical Abstracts; 58, 4714a (1963). However, it has never been known until the present discovery, that when calcium lactate is added to a concentrated aqueous sugar solution (sugar syrup), the syrup is solidified. In addition, the uniformly solidified product obtained in this case is different from the solidified material obtained by drying or heating a sucrose syrup containing no calcium lactate in that the particles of sugar in the former case are very fine.

The present invention has many merits and among them some remarkable advantages as will be described hereinafter.

The sugar-coated tablets prepared according to the method of this invention are superior in impact resistance and humidity resistance to present sugar-coated tablets. Also, the disintegration rate of the sugar-coated tablet immediately after the production thereof is remarkably faster than those produced by conventional procedures and even when the sugar-coated tablets which are obtained by the process of this invention are stored under severe or unusual conditions, the disintegration time is substantially unaffected as said disintegration time is comparable to that noted with respect to sugar-coated tablets tested shortly after they were produced.

Following the new and improved method of this invention, the coating step is conducted by using a single coating composition and it is unnecessary to utilize the conventional manual steps described supra as the composition and the amount of each coating solution is in order to effect each of the conventional manual steps including the undercoating and intermediate coating operations such as sealing, subcoating, rounding and smoothing and the coloring operation. Accordingly, by the method of this invention, the coating operation is simplified and the coating operation is completely automatized at a high speed. Moreover, by the method of this invention, the thickness of the sugar coating layer is sufficient even if it is only about one-half of the thickness of the tablet obtained by conventional procedures is reduced as well as the period of time necessary for forming the sugar coating which is usually shorter than 12 hours. Still further, the sugar-coated tablets obtained show less deviation in weight that is, they are of more uniform weight and are uniform in size. Further, the rate of rejection or percent rejection of the sugar-coated tablets at heat sealing package is low, making the present process most suitable and desirable for commercial production. In addition, calcium lactate is a compound which is acceptable as an additive for foods and provides no physiological difficulties.

Comparative experiments of the sugar-coated tablets prepared by the method of this invention with composite vitamin-containing tablets having sugar coatings formed by the steps of undercoating, intermediate coating and finishing coating using a convention procedure are set out below.

TABLE 1:

When the tablets were rotated in a friability tester at 3,600 rotations, the number of damaged tablets per 100 tablets are shown in the following table, by percent:

Damaged percent (%) ______________________________________ Tablets obtained by the process of the invention 0 Control tablets 25 ______________________________________

TABLE 2:

The amount of loss of surface luster of tablets when they are stored at 37.degree.C and at a relative humidity of 83 percent:

15 day 30 day storage storage ______________________________________ Tablets obtained by the slight slight process of the invention Control tablets largely lost no luster (completely lost) ______________________________________

TABLE 3:

Faded state of tablets when, after applying sugar coating using tartrazine, they were preserved at 37.degree. C and at a relative humidity of 83 percent

15 day 30 day storage storage ______________________________________ Tablets obtained by the scarcely slightly process of the invention changed faded Control tablets almost half almost all were faded were faded ______________________________________

TABLE 4:

Faded state of tablets when, after applying sugar coating using a mixture of tartrazine and new coccine as coloring agent, they were allowed to stand outdoors.

______________________________________ 15 day 30 day storage storage ______________________________________ Tablets obtained by the scarcely slightly process of the invention changed faded Control tablets almost half almost all were faded were faded ______________________________________

TABLE 5:

Period of time required for disintegration by the disintegration test of U.S.P. XII after preserving the tablets for 30 days under various temperature and humidity conditions.

__________________________________________________________________________ Preservation condition Directly at 40.degree.C at 56.degree.C 40.degree.C & After 74% rela- Production tive hum- idity __________________________________________________________________________ Tablets obtained by the process of the invention 4'28" 4'38" 6'56" 4'54" Control tablets 12'06" 21' >50' 20' __________________________________________________________________________

(Note): The period of time required for the disintegration of tablet cores before sugar coating was 2'20".

TABLE 6:

Deviation degree (mg.) of the weight of 100 sugar-coated tablets produced.

______________________________________ Deviation degree (mg) ______________________________________ Tablets obtained by the process of the invention 260 .+-. 2.0 Control tablets 260 .+-. 9.3 ______________________________________

The tablet cores or similar materials to be applied with sugar coating by the method of this invention may be produced in any desired size and shape such as in disc form, doughnut form, spindle form, granular form, etc.

In the practice of the method of this invention, sugars such as sucrose, mannitol, sorbitol, etc. may be used and an aqueous solution of sucrose of about 40 to 70 percent is usually used. The amount of calcium lactate added to the aqueous sucrose solution is less than about 40 percent. In particular, favorable results can be obtained when a coating solution prepared by adding about 3 to 20 percent calcium lactate to about a 60 to 70 percent aqueous sucrose solution is used. Also, if necessary, a tasting agent, a flavoring agent, a colorant, an opaquing agent, a thickening agent, etc., may be desirably added to the coating solution. For applying the coating solution to tablet cores, the coating solution heated ordinarily to about 60.degree.C was sprayed onto the tablet cores in a coating pan in rotation so that the coating solution was uniformly applied and the tablet cores were dried by applying warm blasts of air while rotating the coating pan. In the present procedure, a so-called pausing operation of rotating a coating pan without applying a warm blast of air after applying a coating solution over the tablet cores, which is always employed in a conventional sugar coating step, is unnecessary.

EXAMPLE 1

Sucrose 630g Calcium lactate 100g Distilled Water 270g Tartrazine 1g

After heating 270g of distilled water to a temperature higher than 80.degree.C, 630g of sucrose was dissolved in the distilled water and thereafter 100g of calcium lactate and then 1g of tartrazine were added to the solution to provide a homogeneous coating solution.

After placing 10,000 tablet cores, each having a weight of 150mg in a coating pan and heating the tablet cores by a warm blast, about 30g of the coating solution prepared above was applied onto the tablet cores while rotating the coating pan and after uniformly coating the tablet cores with the coating solution, the coating pan was further rotated while sending a warm blast of about 60.degree.C. By repeating the same procedure, sugar-coated tablets, each having a weight of 200mgs, were obtained over a period of about 3 hours.

EXAMPLE 2:

Sucrose 620g Calcium lactate 40g Gelatin 5g Tartrazine 1g New Coccine 1g Distilled Water 305g

Distilled water was heated to a temperature of higher than 80.degree.C and while stirring the water, gelatin, sucrose, calcium lactate, tartarzine, and New Coccine were successively added to the distilled water to provide a homogeneous coating solution.

Following the same procedure as in Example 1 and using the coating solution thus prepared, sugar-coated tablets, each having a weight of 230 mgs, were obtained over a period of about 8 hours.

EXAMPLE 3:

Sucrose 554g Calcium lactate 91g Gelatin 5g Polytetrafluoroethylene fine particles* 9g Talc 54g Tartrazine 2g Distilled water 260g (*): Particle size 1-5 microns.

Distilled water was heated to a temperature of higher than 80.degree.C and while stirring, gelatin, sucrose, calcium lactate, and tartrazine were successively added to the distilled water. Thereafter, the fine particles of polytetrafluoroethylene and talc were uniformly dispersed in the aqueous solution to provide a coating composition.

Following the same procedure as in Example 1 and using the coating composition, sugar-coated tablets, each having a weight of 260mgs were obtained, over a period of about 10 hours.

EXAMPLE 4

Sucrose 581g Sucrose distearate* 20g Calcium lactate 100g Talc 50g Tartrazine 2g Distilled water 250g (*): Nitto Ester S-770 (trade name, made by Dai-Nippon Seito K.K.)

Distilled water was heated to a temperature of higher than 80.degree.C and while stirring the distilled water, sucrose, sucrose distearate, calcium lactate, and tartrazine were successively added to it and thereafter talc was uniformly dispersed in the solution to provide a coating composition. Following the same procedure as in Example 1 and using the coating composition prepared above, sugar-coated tablets, each having a weight of 200mgs, were obtained over a period of about 3 hours.

Claims

What is claimed is:

1. A coated tablet wherein said coating comprises 40 to 70 percent sugar and 3 to 20% calcium lactate.

2. A tablet according to claim 1 wherein the coating contains about 60 to 70 percent sugar.

3. A tablet according to claim 1 wherein the sugar is sucrose.

4. A tablet according to claim 1 wherein sugar coating syrup colorants, opaquing agents, flavoring agents, thickening agents and mixtures thereof are added.