US3639564A - Method of sugar coating tablets - Google Patents

Abstract

TABLET CORES CONTAINING MEDICAMENTS, PARTICULARLY, HYGROSCOPIC MEDICAMENTS ARE COATED BY APPLYING DIRECTLY THERETO SUGAR SYRUP CONTAINING A SUCROSE HIGHER FATTY ACID ESTER WITHOUT APPLYING WATER PROOF COATING OR OTHER SUBCOATING TREATMENT.

Description

United States Patent 3,639,564 METHOD OF SUGAR COATING TABLETS Ryuichi Kawata and Hiroitsu Kawada, Tokyo, Tadayoshi Ohmura, Niiza, and Sumio Uematsu, Urawa, Japan,

assignors to Yamanouchi Pharmaceutical Co., Ltd.,

Tokyo, Japan No Drawing. Filed Nov. 16, 1970, Ser. No. 90,105

Int. Cl. A01n 17/00; A61k 9/00 US. Cl. 42435 6 Claims ABSTRACT OF THE DISCLOSURE Tablet cores containing medicaments, particularly, hygroscopic medicaments are coated by applying directly thereto sugar syrup containing a sucrose higher fatty acid ester without applying water proof coating or other subcoating treatment.

The present invention relates to a method of coating unpretreated tablet cores directly with sugar syrup containing a sucrose higher fatty acid ester.

More particularly, the invention relates to a method of directly sugar coating tablet cores using sugar syrup containing at least one monoester, diester, or triester of sucrose and a higher fatty acid having 8-20 carbon atoms such as palmitic acid or stearic acid, said ester or ester mixture having a hydrophile lipophile balance (HLB) of less than 11.

In the administration of medicaments and particularly pharmaceutical tablets which are orally administered, to minimize any taste, improve their appearance, and minimize or prevent degradation of the active therapeutic material exposed to high temperature and high humidity while also attempting to minimize damaging the tablet, the usual procedure in dealing with the aforesaid problems has been to apply sugar coating to the tablets.

In conventional sugar coating techniques, it is necessary that the edges and corners of tablet cores be covered or rounded before the finishing sugar coating is applied. This has been done generally by applying an adhesive coating using a composition usually consisting of gelatin, acacia, sugar and water followed by a subcoating powder which rounds off the tablet cores. This subcoating powder is usually a blend of insoluble powders, adhesive powders and lubricants. A typical subcoating powder contains calcium carbonate, talc, kaolin, sugar, acacia, lactose, etc. The application of the subcoating powder requires a high degree of skill and is the most difiicult step of the entire sugar coating operation. It is particularly important for the subcoating layers to be built up evenly and to be dried thoroughly. It will therefore be appreciated that a satisfactory and effective coating over the sharp edges of the tablets is quite difficult to obtain and a large number of individual coatings are required. In ordinary subcoating operations, the time required for building up a suitable subcoating varies greatly according to the skill of the individual coating operator.

Now, when the medicaments present in tablet cores to be sugar coated are highly hygroscopic, and are also easily susceptible to chemical or physical degradation, it is impossible to apply sugar coating to such tablets by usual conventional procedures without applying the subcoating and hence it is required to form a preliminary water proof coating using a water proofing material in addition to the involved pre-treatment described above. Obviously, such a precoating in addition to the pretreatment procedure described above results in a highly involved and time consuming procedure which is most undesirable from an economic point of view. Moreover, when the thickness of the water proof coating is increased Patented Feb. 1, 1972 "ice in order to provide a sufficient antihygroscopic and water proofing effect, the tendency of the tablets to disintegrate is reduced resulting in an excessive period of time which is required to disintegrate the active material in the digestive organs. On the other hand, when the thickness of the water proof coating is reduced for improving the disintegrating property, the medicaments absorb moisture readily during the subcoating and sugar coating as well as after the sugar coating is finished, resulting in degradation or damage to the medicament material.

An object of the present invention is to apply sugar coating directly to tablet cores containing particularly hygroscopic medicaments thereby avoiding such conventional pretreatment steps as water proof coating and subcoating.

Another object of this invention is to provide a coating composition suitable for sugar coating of tablet cores containing hygroscopic medicaments.

A further object of this invention is to apply to tablet cores a stable, sugar coating which causes neither cracks nor degeneration of medicaments by the penetration of moisture during the sugar coating step and after the sugar coating is finished and also causes no exudation of the medimaments material from the inner portion of the tablets.

Still another object of this invention is to apply a sugar coating having good antihygroscopic property in a considerably shorter period of time than is required in conventional sugar coating methods.

It has been discovered that when a sugar syrup containing at least one monoester, diester or a triester of sucrose and a higher fatty acid having 8-20 carbon atoms which is prepared by the method disclosed in US. Pat. 1,959,590 and this syrup is applied to tablets, quite surprisingly, moisture does not diffuse into the inner portion of the tablet cores. That is, when tablet cores are immersed in the coating composition used in this invention, after withdrawing the tablet cores, the coating compositions attached to the tablet cores are wiped away, and the weight of the tablet cores is measured, almost no increase of weight is observed. On the other hand, when a coating composition containing no sucrose higher fatty acid ester is used, the tablet core immersed in the coating composition absorbs water and collapses.

Therefore, according to the present invention, a sugar coating can be directly applied to tablet cores without applying water proof coating even if the medicaments contained in the tablet cores are unstable in the presence of water. Also, in the present invention, sugar coating can be applied effectively to such tablet cores containing medicaments which are unstable in the presence of water without requiring subcoating which is not only technically difficult to apply, requires great skill, but also requires usually a longer period of time.

The pharmacutical tablets thus prepared have good antihygroscopic properties; they can be stored without causing the degeneration of the medicaments in the tablets and cracking of tablets, and also they can be stored for a long period of time without reducing the breaking property of the tablet.

It is known that a sugar higher fatty acid ester is used for emulsions of medicines; or the ester is added to a non-aqueous coating composition or such as ester can be used in aqueous and non-aqueous coating compositions in coating of tablets (Japanese patent publication Nos. 3787/65 now Japanese Patent 456,410 and 1 1845/62) now Japanese Patent 305,633. However, until the present invention, the addition of a higher fatty acid ester to a simple sugar syrup for sugar coating was not known. Moreover, the advantages and surprising results attributable to the use of such a coating were most unexpected.

The shape of the tablet cores to be coated according to the present invention can vary and may be in disc form, doughnut form, a pellet form, a pill form, or a spindle form.

The coating syrup used in the present invention may be prepared as follows: by dissolving or dispersing uniformly sugar and a sucrose higher fatty acid ester in an amount of less than 30% by weight, preferably less than by Weight to the sugar in Water; warm water is preferably used. The sucrose higher fatty acid ester has an HLB of less than 11 and preferably less than 7.

In the preparation of the coating syrup, a coloring agent, a tasting vehicle, a flavoring vehicle, shielding agent, and an extender which are usually used in a conventional sugar coating process may be added if necessary.

The coating syrup thus prepared may be applied to tablet cores by repeating the application and drying of the syrup using the ordinary sugar coating procedure and in this case a high degree of skill generally required in a subcoating procedure is unnecessary, i.e., dropping or spraying of the syrup on the tablet cores in the coating pan and drying. Also, the thickness of the sugar coating may be desirably determined on considering the size of the tablets, the properties of the medicaments contained in the tablet cores, etc.

The sugar-coated tablets prepared by the process of this invention are substantially resistant to the formation of cracks, the occurrence of exuding, etc., under severe conditions of high temperature and high humidity not only during the coating steps but also after the preparation of the coated tablet. Further, there is no change in the time required for disintegration of the tablets after swallowing even after such tablets are stored for an extended period of time as compared with conventional sugar-coated tablets which are prepared by applying sugar coating after applying a water proof coating and a subcoating according to the usual techniques.

The invention will be illustrated by the following nonlimitative examples.

EXAMPLE 1 Composition: G. Sugar 9 50 Sucrose distearate 1 75 Water 450 r KNitto ester S-770, trade name, made by Dninippon Seito Procedure-After heating 450 g. of water above 80 C., 950 g. of sugar and then 75 g. of sucrose distearate having an HLB of 7 were added slowly to the water, with stirring, to provide a homogenous coating composition. In a coating pan were placed 10,000 tablet cores each weighing 150 mg. and while rotating the coating pan, about g. of the coating composition prepared above was applied onto the tablets. The coated tablet cores were then dried, in air at a temperature of about 50 C. By repeating the same procedure, sugar coated tablet cores each weighing 300 mg. were obtained.

EXAMPLE 2 Composition: G. Sugar 950 Sucrose distearate 50 Talc 75 Water 500 Procedure.After heating 500 g. of water to 90 C., 950 g. of sugar, 50 g. of the sucrose distearate used as in Example 1, and 75 g. of talc were added to the water, with stirring, to provide a homogenous coating composition. By repeating the same procedure as in Example 1, about 10,000 tablet cores each weighing 150 mg. were obtained; sugar coated tablets each weighing 230 mg. were obtained.

4 EXAMPLE 3 Composition: G. Sugar 950 Sucrose mono, distearates 1 50 Water 450 I kNitto ester S1170, trade name, made by Dainippon Seito After heating 450 g. of water above C., 950 g. of sugar and 50 g. of sucrose mono, distearates having an HLB of 11 containing about 50% mono-ester, 30% diester and about 20% tri-ester were added slowly to the water, with stirring, to provide a homogenous coating composition. Following the procedure of Example 1, about 10,000 tablet cores each weighing mg. were obtained; the sugar coated tablets each weighing 300 mg. were obtained.

EXAMPLE 4 Composition: G. Sugar 950 Sucrose distearate 50 Titanium oxide 10 Tartrazine aluminum lake 10 Water 500 After heating 500 g. of water above 90 C., 950 g. of sugar and then 50 g. of the sucrose distearate as in Example 1 were slowly added to the water, with stirring, and then 10 g. of titanium oxide and 10 g. of tartrazine aluminum lake were uniformly dispersed in the solution to provide a homogeneous coating composition. Following the procedure of Example 1 about 10,000 tablet cores each weighing 150 mg. were obtained; the sugar coated tablets each weighing 300 mg. were obtained.

EXAMPLE 5 Composition: G. Sugar 340 Sucrose distearate 25 Talc 25 Tartrazine 1 Water 109 After heating 109 g. of water above 90 C., 340 g.

of sugar and then 25 g. of sucrose distearate and 25 g. of talc, as in Example 1, were slowly added to the water, with stirring, and then 1 g. of tartrazine was uniformly dispersed in the solution to provide a homogeneous coating composition. Following the procedure of Example 1 about 10,000 tablet cores each weighing 150 mg. were obtained; sugar coated tablets weighing mg. were obtained.

The following experimental tests confirmed the excellent results attributable to the present invention.

Specimen: The sugar-coated tablets prepared by the method of Example 2.

Control specimen: The sugar-coated tablets prepared by applying water proof coating of shellac to tablet cores and then applying a coating of a mixture of sucrose, a binder and a suspensible powder thereto.

The following tests were applied to 100 tablets of each of the specimens and the control specimens and the results are shown in Tables 1-3.

Test 1 TABLE 1 Days stored 15 30 60 Specimen 0 0 0 Control specimen- 0 100 100 Test 2 After storing at a temperature of 45 C. and a relative humidity of 74%, the number of the cracked tablets was detected. The results are shown in Table 2.

TABLE 2 Days stored 30 60 Specimen 0 Control specimen". 25 100 Test 3 After storing for 20 days at a temperature of 45 C. and a relative humidity of 40-60%, the disintegration time (in minutes) of the tablets was measured by using artificial gastric juice according to the U5. Pharmacopoeia (U.S.P. XVII) and the mean value was calculated. The results are shown in the following table.

TABLE 3 Days stored 0 20 Specimen. 12 14 Control speeimem- 25 40 free of tendencies to crack and to retard disintegration time consisting essentially of an aqueous sugar syrup and an effective water-proofing and anti-hygroscopic quantity of a sucrose 8 to 20 carbon atom higher fatty acid mono-, dior tri-ester having a hydrophile-lyophile balance of less than 11.

2. A tablet according to claim 1 wherein sugar coating syrup colorants, opaquing agent, flavors and mixtures thereof are added.

3. A tablet according to claim 2 wherein a tartrazine aluminum lake colorant and tri-ox'ide opaquing agent are added.

4. A tablet according to claim Lwherein the fatty acid ester is derived from stearic acid.

5. A tablet according to claim 1 wherein the fatty acid ester is a mixture of the mono-, diand tri-esters of stearic acid.

6. A tablet according to claim 1 wherein the fatty acid ester is derived from a mixture of stearic and plamitic acids.

References Cited UNITED STATES PATENTS 2,893,990 7/1959 Hass et al. 260-234 3,931,802 4/1960 Touey et al. 260-234 2,948,717 8/1960 Babayan et a1. 260-234 3,057,743 10/1962 Touey et al. 106-162 X 3,108,977 10/ 1963 Wolff 260234 X 3,160,565 12/1964 Duell 260147 3,495,998 2/1970 Reeves et a1. 106-462 X SHEP K. ROSE, Primary Examiner US. Cl. X.R.