US3331696A - Dragee coating composition - Google Patents

Description

July181967 P. RIECKMANN ETAL 3,331,595

DRAGEE COATING COMPOSITION Filed Jan. 16, 1965 2 Sheets-Sheet l DRYER.

TlilER COMPRESSED AIR. I

/6 IJ-Tf INVENTOR:

Y PETER /z/EcKMA/v/v .1 .1' E-L HE/Nz scHA/ K ECKHARD THEEL July v18, 1967 Filed Jan. 16. 1963 F. RIECKMANN ETAL DRAGEE COATING COMPOSITION 2 Shee'Is-Sheet L' I 1 l., soLENoIo FUSE DRYER lIFUSIE PETER //EC/CMANN HE/NZ SCI-MLK EC/{HARD THEEL INVENTORS United States Patent O 2 claims. (ci. 10s-20s) The present invention relates to a process for the manufacture of drages and to an apparatus therefor. In one aspect it relates to an automatic process for rapidly manufacturing pharmaceutically acceptable drages.

It is known that the drage represents one of the most wide-spread forms in which drugs are administered, and Y that the administration of drugs in this form is growing in popularity. Drage preparations are characterized by the advantages that they are easy to ingest and eliminate the bad taste which is characteristic of so many drugs. Furthermore, the drage is a particularly important vehicle for use in connection with drugs which are sensitive to light, air, and moisture. Still further in the case of drugs which have a disturbing effect on the stomach or which are inactivated in the stomach, special coatings can be applied so that the drage will not dissolve until it reaches the intestines, resulting in excellent tolerability and permitting the oral administration of drugs not possible in the absence of such coatings. Y

The manufacture of drages suitable for commercial utilization involves many diiculties. As heretofore carried out, it is a manual art requiring much practice, skill, and experience. The pill or center coming from the tablet forming machine has first applied thereto where necessary, isolation coatings which act to protect the pharmaceutical substances from external influences. The pill or center is then coated with a sugar syrup of a certain composition and thereafter with mixtures of talc, chalk and like solid fillers. This process has to be repeated several times in order to apply to the pill as quickly as possible sufficient material to produce on the drage edges which are rounded. However, the surface of the pill so obtained is not smooth and has to be smoothed out in further steps, using therefor both sugar Syrups and powdered sugar. The smoothing step is followed by coloring steps, whereby a uniformly colored drage is achieved only following the application of many coats of colored sugar syrup. Finally the drages are waxed or glazed. Between each of the individual steps in the process, the drages are taken from the coating treatment kettle and dried in large drying machines or ovens so that the moisture necessary in connection with the coating applications cannot penetrate through the covering and damage the drugs forming the center or core.

The process as described above requires a great deal of hand work by experienced personnel. A particularly serious disadvantage is the need to keep the drages in motion in the kettle by stirring them by hand until they no longer stick to one another or to the kettle. Another difculty lies in that the process consumes an enormous amount of time. The drages are required to spend a total of about t-wo days time in the -kettle with additional time for periodic interruptions required for drying between each step in the process. In al1 a total of 8 to 10 days 3,331,696 Patented July 18, 1967 production time is required for producing each batch of drages.

Methods for rapidly coating pills have become known in recent years in connection with which it has been proposed that all of the substances to be applied to the pills be combined in 4a single, sugar-coating suspension. Such a process has, for example, been described in German Patent 1,000,569 and is carried .out using a coating suspension consisting of water, sugar, starch and sodium cellulose glycolate with heat. While this process has been somewhat successful, it has not gained wide-spread usage as it produces satisfactory results only if the coating process is constantly supervised (see Gstirner, Grundstoffe und Verfahren der Arzneibereitung, Verlag F. Enke, Stuttgart 1960, page 61). The constant supervision required represents a considerable disadvantage in comparison with the conventional coating process described hereinbefore in which the kettles do not have to be kept under constant supervision and observation.

Other rapid coating rapid processes have been proposed which are based upon the complete elimination of the use of sugar, the coating being performed, for example, using alcoholic solutions of polyethylene glycol (see Gstirner, loc. cit., page 62). Polyethylene glycols, however, have the signiticant shortcoming that they are particularly bad tasting. The use of drages produced with alcoholic solutions of polyethylene glycol is disagreeable to the patient and, therefore, do not offer the advantages associated with this form of drug administration.

It is accordingly the general object of the present invention to provide a method for the manufacture of drages which are of a purity surface, smoothness, taste, and color suitable for commercial use in an economically feasible manner.

Another object of the invention is to provide a method for the manufacture of drages which are of a purity, surface smoothness, taste, and color which makes their use convenient and inexpensive without any disagreeableness to the patient who has to take repeated doses of the pharmaceutical contained in the drage.

Still another object of the invention is to provide a substantially automatic method for the manufacture of drages.

Still another object ofthe invention is to provide a rapid method for the manufacture of drages.

Still a further object of the invention is to provide an apparatus for the manufacture of drages which are of a purity, surface smoothness, taste, and color suitable for commercial use.

It is still another object of the invention to provide drages, i.e. an improved vehicle for therapeutic compositions being characterized by stability, surface smoothness, pleasant taste, etc., and whereby the full effect of the therapeutic mechanism can be carried out when the composition is administered orally.

Still a further object of the invention is to provide coating suspensions for coating drages, containing polyethylene glycol in addition to sugar and filler materials in aqueous suspension.

Other and furthe-1' objects and advantages ofthe invention will become apparent to one skilled in the art upon referring to the accompanying disclosure and the drawing in which: 1

FIG. 1 is a schematic illustration of one preferred embodiment of the apparatus of the invention,

FIG. 2 `isa schematic illustration of another preferred embodiment of the apparatus of the invention.

FIG. 3 is a diagrammatic representation of the wiring of an embodiment of the apparatus shown in FIG. 2,

FIG. 4 is a schematic illustration of another preferred embodiment of an apparatus of the invention showing in particular the use of a hand dryer as a source for heated air, and

FIG. 5 is a diagrammatic representation of the wiring of the embodiment of FIG. 4.

In accordance with the present invention a fully automatic rapid method for the production of drages characterized by pleasant taste, smoothness of surface, and perfect color has now been found. It has been found according to the invention that when pill centers or cores are coated usingan aqueous-sugar coating suspension containing l-lO weight percent of polyethylene glycol in addition to 40-50 Weight percent of sugar and 10-20 weight percent of solid llers, ydragees are obtained characterized by the properties as just set out. In preparing the drages,

t the coating suspension is sprayed onto the pills or centers maintained in rotation in a coating kettle, the spraying interrupted and the sprayed drage centers maintained in amount which` could be keptV broken up and moving by hand, the kettle in accordance with the invention can be lled to its maximum capacity. A special advantage stemming from the process of the invention lies in the fact that each coating which is applied is a relatively thin coating, is dried immediately and consequently no penetration of moisture into the center during the coating process takes place. Since smooth coatings are formed from the start, the total or over-all coating can also be much thinner than usual. The coatings in accordance with the invention amount to approximately up to 1%. times the weight of the center where formerly the coatings Vamounted to about twice the weight of the center.

The coating suspensions of the invention per se are novel and can be produced very simply without heat merely by stirring the components together and homogenizing the resultant suspension, for example in a corundum disk mill or the like; In Table l, which follows, illustrative examples of a number of coating suspensions according to the present invention are set out. It is possible in accordance with the invention to add coloring material from the start of the process if desi-red, thus achieving a uniform coloration of the drages.

TABLE 1 Examp1e Sugar Carbowax 1 6000- Carbowax 1 20000 l Starch syrup. Gum arabic Chalk Kaolin Talnnm Titanium oxide Tricalcium phosphate.. Coloring 2-.-. Water to make $203 NMA rotation for a period of time and thereafter the coated centers dried with a current of warm air. These three steps in the sequence as set out are repeated, if necessary, until the desired total amount of coating suspension has been applied.

In this way and namely by the incorporation according to the invention of a small amount of polyethylene glycol in a sugar-containing coating suspension, the tendency to stickiness .at the start ofthe drying of the suspension is overcome, that is the drages do not stick to one another nor do they adhere to the kettle Wall. There is, as a result,

made possible a rapid, fully automatic pill center coating process. The invention makes possible for the first time the possibility in a single operation to applythe coating suspension onto the pill center and to dry the same thereon. In the process as herein taught, the need for handwork is eliminated other than that which is required for adjusting the equipment at the beginning and at the end of the process. Further, the requirement for experienced technicians to carry out the process is eliminated. Furthermore, drying ovens are no longer required whereby the frequent transporting of the drages from the kettle Vto the drying oven and back which represents a serious disadvantage of the coating'processes as conventionally practiced is eliminated. A further considerable advantage ofthe instant process is that the time required for production of a batch of drages amounts to only about one day. In connection with the production time, it should be noted that the capacity per kettle is many times that of the conventionally practiced process. Thus, whereas in the known conventional method, the kettle char-ge was limited to that 1 Trade name of polyethylene glycol. 2 =quantum sulet.

The following examples illustrate satisfactory procedures for the manufacture of drages, but it is to be understood that they are presented only for the purpose of illustration and not as indicating the limits of the invention.

Example 1 8 kilograms of drage centers of 6 mm. diameter (weight of centers 8O mg., number of centers 100,000) are introduced into a kettle having a 60 cm. diameter provided with a powerful exhaust system. The spraying system is adjusted so that about ml., of the coating suspension are sprayed onto the centers within a period of 25 seconds in each of the coating steps. The centers are circulated, i.e. rotated for 1.5 minutes following the spraying without any external interference so that thek suspension can be uniformly distributed on the surface of the drages. The batch is then dried with a current of -hot air for 2 minutes. These three steps are repeated until 8.5 kg. of suspension Vhave been applied. The coating suspension employed is-one in accordance with the invention containing polyethylene glycol in addition to sugar and solid llers. The drages which have had smooth coatings Vfrom the 4start of the procedure are now Vready for Waxing. The total production time `amounts to aboutYV 6.5 to 7 hours and no supervision of any kind is required in this period. After the coating has been completed, the drages have a weight of Ing.V The coating dissolves in the Erweka disintegration tester in about 4 minutes which is comparable with a very good candy coating as formed by the process as used hitherto.

Examples 2-5 The process of Example 1 was repeated, the data and results of these coating operations as carried out in accordance with the process of the invention are set out in Table 2 which follows:

TABLE 2 Drage Centers 1 spray coating i Drage Tota Wt. Diam., Wt., Wt. (mg.) Sus- Dry mm. mg. Number pension Weight (mL) (g.)

Time per spray coating (sec.) Total Kettle Candy Diameter Coating (cm.) Spraying Pause Drying a-l-b-t-c Time (a) (b) (C) (hrS-) The rapid, fully automatic process of the invention can preferably be carried out using the novel apparatus taught in accordance with the invention.

Referring to FIG. 1, the apparatus according to the invention which is particularly suitable for carrying out the fully automatic coating process consists of three separate systems:

(A) a spraying system composed of a spraying nozzle 1 which is connected by conduits 3, suitable valves or pumping switches 2 to a supply tank 4 containing the coating suspension;

(B) a source of heated air 6 provided with suitable switches and conduits S and 9 respectively and (C) an electrical control apparatus composed of a timer mechanism 7.

In one embodiment of the invention are shown in FIG. 2 a spray gun 13 such as is conventionally used for spray painting is used for spraying the coating suspension. The advantage of using a spray gun of this type is based on the fact that it is provided with a proportioning valve so that different amounts of coating suspension can be applied at a constant time setting. A possible disadvantage, however, is that compressed air is required to be used therewith resulting in the formation of mists which are removed from the system through an exhaust line and representing suspension not deposited on the drages.

Another possible disadvantage is that spray guns are not self-feeding so that the coating suspension has to be fed positively to the gun as for example by gravity (FIG. 2), i.e. from the vessel 11 downwardly through suitable conduits to the gun 13.

The wiring diagram showing the relationship of the timer mechanisms 17 to the remaining apparatus of FIG. 2 is shown in FIG. 3.

For these reasons, it has proven advantageous to supply the coating suspension at a pressure of 10 atmospheres using therefor a gear pump. As shown in FIG. 4, by means of an electrically controlled three-way valve 23, the coating suspension maintained under pressure in vessel 21 is either fed to the spray nozzle 25 or is carried back through an over-pressure valve 26 into the supply vessel 21. Although the coating suspension of the invention generally is not inclined to settle out, it has nevertheless proven advantageous to avoid any possible formation of sediment by agitating the suspension. Under the circulation produced by the gear pump, of course, no other agitating system is required. The electrical control of the spray gun is carried out by means of a solenoid 23 which actuates the trigger resulting in spraying. If a. gear pump and spray nozzle are used, the control is carried out by means of commercially available magnetic three-way valves.

A hair dryer, as shown in the embodiment of FIGS. 2 and 3, for example, can be used as a hot air source for small kettles. Even for large kettles, the output of a standard hand dryer is adequate (see FIGS. 4 and 5 Of course, any other hot air source can be used for drying as long as it provides the assurance that the temperature and rate of ow of the air are constant.

The timing regulation for the apparatus described above is carried out in a known manner utilizing the conventionally available electrical timers. These contain, for example, revolving cams which open and close the necessary contacts. It has proven advantageous, however, to be able to adjust accurately the spraying time, the inactive period, and the drying time, and this is done by means of three-time switching mechanisms. When separate switching mechanisms are used, the running time can be adjusted during operation which is not directly possible in the case of cam-operated timers.

The apparatus described above can, if desired, be combined into a very practical readily movable unit as has been shown in FIG. 1. The apparatus is connected With single-phase or three-phase current source by means of a single cable. If the hot air unit is not built in, a control line is required for the hot air in-feed.

Aswused herein the term carbowax designates the trade name of a gnoup of non-volatile, solid, polyethylene glycols, soluble in both water and aromatic hydrocarbons and which are manufactured by Carbide and Carbon Chemical Company, a Division of Union Carbide and Carbon Corporation of New York City, New York. Carbowaxes are supplied in various grades, the grades being designated by numerals as shown in the specification. Increasing grade numbers indicate increasing molecular weights.

Illustrative examples of the coating suspensions according to the present invention have been shown in Table 1. Of course, many changes and variations in the components may be made by those skilled in the art in accordance with the principles set forth herein. Naturally, we make the limiting statement to the effect that the components of the coating suspension must be nontoxic, at least in the amounts in which the same are employed.

The preferred procedure for the manufacture of drages according to the present invention has been shown in Examples 1-5. Of course, manychanges in -the reaction conditions, temperature and duration may be made by those skilled in the art in accordance with the principles set forth herein. The drying of the drages is effected by means of hot air of -120 C., preferably. In case that the drage center may contain some heat sensitive material, the drying may be effected also at lower temperatures, whereby the duration of that step will last longer, naturally. In general, the time ranges for each of the steps of the coating process according to the present invention depend on the size of the kettle as well as that of the drage centers, of the humidity of the atmosphere and the like conditions. Preferably, the `spraying step has a duration of 5-50 sec., the pause 10-100 sec. and the drying step 50-200 sec.

The apparatus for effecting the manufacture of the drage according to the present invention is composed of a number of parts known per se. However, as special 7 arrangement of those components-as shown in the accompanying drawings-is necessary to guarantee an absolutely perfect coating process. Y

What is claimed is: 1. A drage coating composition for coating pill centers consisting essentially of an aqueous sugar solution containing 40-50 weight percent of sugar, 1-10 weight percent of polyethylene glycol and 10-20 weight percent of an inert solid ller wherein said solid filler is a member selected from the group consisting of starch, gurnarabic, chalk, Vkaolin, talc, titanium oxide, alkaline metal phosphates and mixtures thereof. Y

2. A coating composition according to claim 1 additionally containing a colorant.

8 f References Cited UNITED STATES PATENTS 632,014 S/ 1899 Hackelberg 106-162 751,981 2/190'4 Gordon 106-162 2,217,020 10/1940 Jurgens et al. 118-25 2,472,650 6/ 1949 Curlee 118-25 2,540,253 2/1951 Gakenheimer 167-57 2,991,226 7/1961 Millar et al. 167-82 3,030,273 4/ 1962 Zagnoli 167-82 3,073,748 1/1963 Utsumi et al. 167-82 ALEXANDER H. BRODMERKEL, Primary Examiner.

I. S. LEVI'IT, DANIEL ARNOLD, G. A. MENTIS,

Assistant Examiners.

Claims (2)

1. A DRAGEE COATING COMPOSITION FOR COATING PILL CENTERS CONSISTING ESSENTIALLY OF AN AQUEOUS SUGAR SOLUTION CONTAINING 40-50 WEIGHT PERCENT OF SUGAR, 1-10 WEIGHT PERCENT OF AN INERT SOLID FILLER WHEREIN SAID SOLID FILLER IS A MEMBER SELECTED FROM THE GROUP CONSISTING OF STARCH, GUM ARABIC, CHALK, KAOLIN, TALC, TITANIUM OXIDE, ALKALINE METAL PHOSPHATES AND MIXTURES THEREOF.

2. A COATING COMPOSITION ACCORDING TO CLAIM 1 ADDITIONALLY CONTAINING A COLORANT.

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