Patented Oct. 24, 1950 2,526,683

UNITED STATES PATENT OFFICE 2,526,683 METHYL. CELLULOSE CAPSULES AND PROCESS OF MANUEFACTURE Hubert W. Murphy, Indianapolis, Ind., assignor to Eli Lilly and Company, Indianapolis, Ind., a corporation of Indiana . No Drawing. Application April 13, 1946, Serial No. 662,102 6 Claims. (Cl. 167-83) This invention relates to medicinal capsules lower end of the temperature curve, the viscosity and more particularly to capsules of etherified of these cellulose derivatives decreases with a rise cellulosic material such as methyl cellulose, and in temperature through a relatively narrow range to methods of manufacturing the same. of low temperatures, and then increases rapidly For over a century capsules have been made 5 through an exceedingly narrow range of rising almost universally from gelatin despite the fact temperature with gel formation a few degrees that the manufacture and use of such capsules above the temperature at which minimal vis are attended with difficulties. While alternative cosity is displayed. materials, such as cellulose acetate, have been The methyl cellulose I employ in making my proposed for use in capsule manufacture, and 10 nOWell medicinal capsules is of a type having an while such proposed materials may not be sub unusually low intrinsic viscosity, advantageously ject to certain of the deficiencies and defects pos in the range of about 7 to 15 cps. (centipoises) in Sessed by gelatin capsules, other difficulties, prin trinsic viscosity. (By intrinsic viscosity is meant cipally in the manufacture of the capsules, are the Wiscosity displayed under certain standard encountered. 5 conditions, arbitrarily chosen as 2 per cent con Objects of this invention are to provide medici Centration in distilled water solution at 20° C.) nal capsules which have substantial advantages In this range I prefer to use methyl cellulose over prior capsules, both in general utility and types of about 8 to 10 cps. intrinsic viscosity. in manufacture, and to provide a convenient and AS exemplified, there is employed in the mak rapid process for their manufacture. 20 ing of my capsules, methyl cellulose with a Medicinal capsules provided in accordance methoxyl content of about 30 percent and which with this invention are prepared from a readily When dissolved in distilled Water at a concentra available and inexpensive material. They are tion of 2 percent yields a solution which displays non-toxic. In contrast to capsules made from an intrinsic viscosity of about 9 cps. at 20°C. cellulose acetate or gelatin, they do not become 25 The intrinsic viscosity characteristic of the soft or sticky or acquire an unpleasant taste or methyl cellulose is a very important factor. in odor when exposed to relatively high humidity. determining the rate of mass production of cap Furthermore they do not become dry and brittle Sules. For example, it requires about 10 times when filled with materials having hygroscopic as long for the formation of capsules from a properties or when exposed to air of low humid 30 coating composition prepared from a methyl ity. They retain their strength and form even cellulose of the 15 cps. intrinsic viscosity type as when containing compositions of relatively high it does from a coating composition prepared from or low pH. They are not attacked by micro the 9 centipoise type. Moreover, it has been organisms such as molds, as frequently happens found that whenever the intrinsic viscosity char with gelatin capsules, especially when exposed to 35 acteristic is decreased much beyond that of the warm and humid atmosphere. They are sturdy 7 centipoise type, the quality of the capsular wall, and withstand, without fracturing, the mechani particularly with regard to tensile strength, elas cal shocks encountered in ordinary handling, and ticity, and yield point, is excessively reduced and in filling and packaging Operations. They are otherwise seriously affected. readily disintegrated when taken internally, thus 40 In the production of methyl cellulose capsules, making available their medicinal contents. Fur I prepare a clear, substantially bubble-free coat ther, the time required for disintegration may be ing composition desirably containing from 15 to controlled within limits. They may be made in 20 percent of a low viscosity type methyl cellu a wide variety of colors and may be made opaque lose. This is accomplished, for example, by or clear as desired. . treating 5.2 kg. of low Wiscosity methyl cellulose, The medicinal capsules provided by this in 45 designated as 9 centipoise type, with 27 liters of vention are prepared from methyl cellulose which boiling water to facilitate wetting of the cellu is soluble in cold Water, insoluble in hot water, lose particles. This mixture is then cooled and and possesses peculiar gelling characteristics. maintained at a temperature of about 5° C. for Water solutions of such methyl cellulose vary in 12 to 24 hours during which time complete solu viscosity with temperature changes in a way 50 tion of the methyl cellulose takes place. If air quite different from gelatin solutions. Whereas bubbles persist, they can be removed by subject the viscosity of gelatin solutions continuously de ing the solution to vacuum, but in most instances creases with rising temperatures through a rela this will not be necessary. This coating compo tively wide range, with the gelation point at the sition is very stable and can be stored at about 2,526,683 se 4. 10° C. for months without being attacked by the size of the capsules being formed and is some microorganisms or apparent change in Wiscosity. What longer for the larger capsules. With meth At 15 percent concentration, such a solution of y cellulose of the 15 cpS. intrinsic viscosity typ2 methyl cellulose has viscosity of about 8000 cps. there is required about 75 seconds to dip and coat at 2°C. and 4500 cps. at 18°C. the piis for the Standard No. 0 capsule. With This composition is used to coat capsule-form coating compositions prepared from methyl cel ing members, such as round-ended, highly pol lulose of 9 cps. intrinsic viscosity type, the vis ished, stainless steel pins, by dipping then into cosity of the coating composition is such that the the composition for a few Seconds. time of dipping and coating is about 7 or 8 Sec It is desirable to maintain the coating composi () onds. The coated pins are then transferred to a tion at a temperature a few degrees below the drying kiln, while being at first rapidly and then temperature at which it displays a minimuli vis more slowly turned on a median horizontal axis cosity because there is a very rapid rise in vis of their Supporting member thus evenly distrib cosity and subsequent gel formation if the ten uting the relatively small flowable portion of the perature is raised only a few degrees beyond this coating. A period of about 35 seconds usually point of minina value. In genera, temperatures Serves to obtain. Substantially complete gelation. Within the range of about 5 to 29° C. Will be en Desirably the drying kiln is so constructed that ployed. The clear, pubiole-frea coating connoSi a method of ZOne drying is obtained While a cur tion described above desirably is laintained at 3. rent of warm dry air is slowly passed over the temperature of about 3 C. during the Coating coated pins. Thus for about the first 30 minutes operations. in their paSSage through the kiln, the coated pins Before being inaire'sed in the coid rethyl cel are subjected to a temperature of about 40° C. lulose solution, the capsule-forning pirs are Slit and after this period, they advance in the dry ably heated to a, teilerature SubStaitially above ing kiln into Successively Warmer regions or Zones the gelation point of the solution employed. Wit. . until a tenperature of about 60° C. is obtained the specific composition described above, a in about 45 minutes after they have entered the temperature of about 65° C. desiray is eimployed, kiln. The movement of air through the kiln is and this ten perature cases3. rapid geting of the directed from the lower temperature region to composition in contact with the pins. It has heen the higher temperature region. Infra-red radia found that by Operating under these coinditions, tion may also be used in drying the capsular ele a very unifolim capsular Wall is obtained, largely ments on the pins. With the aid of infra-red because that portion of the coating Congosition lamps, the time of drying the capsules is only which immediately surrounds that portion gelat about 50 minutes, this time being dependent to ing on the capsule-forining pin is heated Stifi Some extent upon the concentration, intriinsic Ciently (as Will be hereinafter desi3ribed) to bring Wiscosity and thickness of the methyl cellulose. it to the temperature at Which the lowest vis After drying, the capsule-forming pins bear cosity is displayed. A. Cing Gthe things, this ing the methyl cellulose capsular elements are causes free draining of excess coating material

desirably allowed to cool to about room tempera from the pias whei aire withdrawn, and c2n-. ture which effects slight contraction of the cap tributes to the lilifori8 distribution of the Coat:- 4. Sule-forming pins and thereby promotes easier ing on the pins. removal of the methyl cellulose capsular ele A plurality of capsule-forming pins can be ments. These capsular elements are stripped Coated in one dipping operation and conveniently from the capsule-forming pins, cut to appropri the entire instal portion, including the pins and ate Size, and the bodies and caps assembled as the bar on which they are noted, is heated to Capsules. These operations may be performed Susch a degree that eacgiaten heat, is retaired Inanually, or mechanically on appropriately de by the metal therei to gelate substantialiy all the Signed machines. coating Composition adherent to the capStie The capsules obtained by this process consist forming pins Within an interval of aibout 35 sec essentially of methyl cellulose and when in equili onds after they have been removed from the coat brium with air of 40 per cent relative humidity ing. CorpOSition. While the temperature to which at 20° C., contain about 2.5 percent of water by the metallic goition including the capsule-form Weight. At higher relative humidities, the cap ing pins must be preheated will vary, as for dif Sule Will gradually absorb more Water and if ferent sizes of Capsules, generally it will fall With maintained at a relative humidity of 90 percent, in the temperature range of about 4G to aboli, 55 for 48 hours or more, as much as 20 percent of 80° C. Moreover, it is also possible to control, to Water may be absorbed. a limited extent, the thickness of the capsule Wail Although these capsules are satisfactory for by varying the temperature to which the metal many purposes, I have found that they can be lic portion is preheated. improved by the addition of an essentially non The Surfaces of the capsule-forning pins de 60 toxic plasticizer to the capsule-forming composi sirably are very Smooth and highly polished and, tion, designed to impart to the capsules made although a lubricant, for them is not essential, it therefron greater flexibility and to prevent ex has been found advantageous in order to facili cessive hardness and loss of flexibility whenever tate removal of the capsular elements therefroin, hygroscopic medicaments are enclosed therein, to precoat the CapSulie-forming pins with a very 65 and to aid in obtaining more rapid disintegration thin uniform filiin of lubricant before they are in of the capsule in the digestive tract of a patient. merSed in the Coating composition. A suitable There are a very large number of plasticizers lubricant comprises a mixture of equal parts of which can be used for this purpose among which SOft SOap U. S. P. and anhydro LS anolin with G. may be mentioned: Sucrose, invert sugar, dextose, percent chronium trioxide. 70 glycerol, lower alkyl fatty acid monoesters of The heated and lubricated capsule-forming glycerol Such as monacetin, monoethers of glyc pins are dipped to the required extent in the erol such as glycerol a-methyl ether, a- and B Cold methyl cellulose coating composition to form gluco heptonic acid and/or their lactones, and a coating thereon, and are then withdrawn. The their lower alkyl and glycol esters, glucono-A- time l'equired in the dipping operation varies with 75 lactOne, y-Valerolactone, a -amino acids such as 2,526,683 S 6 glycine, ethyl glycinate, amines such as mono flexibility than those made from methyl cellu ethanolamine and triethanolamine, glycols such lose alone. The approximate composition of as propylene glycol, triethylene glycol, 2-ethyl these capsules when at equilibrium with air of 13-hexanediol, 1,3-butylene glycol, glycosides 40 percent relative humidity at 20° C. Was: meth such as a-methylglucoside, acetopropanol, an yl cellulose 97 percent, monacetin 1.2 percent, and ides such as acetamide and propionamide, Sorbi water 2.1 percent. tol, mannitol, lactose, and lower alkyl phosphates Eacample 2 such as triethyl phosphate. m The selection of an appropriate plasticizer or 5.2 kg. of 9 centipoise type methyl cellulose are treated with a hot solution of 150 g. of Sorbi combinationtion of the a oflot plasticizers to be used and willthe bedetermina governed - 10 toll in 27 liters of Water, and the resulting mix es.certainine Wibe essentially considerations: non-toxic; that the that amount it be turecomposition is then cooled.possessed Capsules greate prepEd.flexibility forand isis oppreciably volatile that it does not impart solved much more readily in artici Eli a disagreeable odor or taste to the capsule; and 15 J than those prepared from methyl cellulose thatchoice it beof inexpensiveplasticize is and further readily governed available. to someThe alone.methyl celluloseFor example, alone capsulesruptured prepared and liberated from eycynicroorganisms; the following factors: its influenceits freedom on from the theposed medicaments to the action contained of artificial therein. gastriotice When ex. at amont of water absorbed by the capsular film 20 37 C. in approximately 10 minutes, it cap a high relative humidities the nature of the sules prepared from the Smelot of methyle medicament to be dispensed within the capsule; lulose with the addition of SOrbitol, aS described theand effecttoughness desired of onthe thecapsular hardness, wall; flexibility, and the inabove, approximately ruptured and 5 liberated minutes. their These medicaments capsules rapidity of disintegration desired after adminis-25 when in equilibriu. Withai of 40 percentre tration of the capsule. tive humidity at 20° C. had approximately the In general, for semi-rigid capsules, I prefer following composition: methyl cellulose 94.3 per to use not more than 5 percent of a plasticizer cent, sorbitol 3.3 percent, and Water.3 percent. (based on the weight of the dried capsule) and At high relative humidities these capsules dis ethylphosphate,have found invert sugar,and sorbitol manitol, to monacetin, be the most tri- so playedthose plasticized a greate withtendency monacein, to absorb Water than generally useful. Whenever the capsules are to It is frequently desirable to prepare colored be exposed to an atmosphere of high relative and/or opaque capsules in order to serve as a humidity, mannitol, monacetin and triethyl phoS- means of identification, to protect the ingredients phate are superior to invert Sugar or Sorbitol be-, 35 thereof from the destructive action of light, or cause the former promote minimal absorption of merely for aesthetic purposes. Methyl cellulose Water in the capsular wall. Invert Sugar and is very satisfactory for the preparation of cap Sorbitol, on the other hand, promote more rapid sules of this type and in many instances is Supe disintegration of the capsule in the digestive rior to gelatin. Generally, the gelatin used for tract. More rapid disintegration may also be 40 the manufacture of capsules is treated with Sull effected by incorporating in the coating composi fur dioxide to improve its clarity. However, the tion Small quantities of electrolytes, for exam sulfur dioxide remaining in the gelatin (or by ple, salts of organic acids such as benzene Sul - products resulting from this treatment) fre fonic acid, toluene sulfonic acid, citric acid, and quently effect a deleterious action on certain the like. colorants Such as ponceau-SX. Methyl Cellulose The process for the preparation of plasticized on the other hand requires no corresponding methyl cellulose capsules is essentially the same clarifying treatment, and appears to have no as that used for methyl cellulose alone although deleterious effects on colorants. Furthermore, When the amount of plasticizer is relatively large, Since methyl cellulose can generally be utilized it is desirable to perform the coating and gela 50 with substances within the pH range of 3 to 10, tion operations at slightly higher temperatures. in contrast to the narrow range Which must be The plasticizer can be incorporated in the meth maintained with gelatin, one is permitted greater yl cellulose solution in a number of convenient freedom in the choice of colorantS and is able ways, such as by adding it to the methyl cellu to obtain different hues from the same colorant lose and then treating the mixture with boiling 55 by taking advantage of the effect of pH changes water, by dissolving the plasticizer in the water in producing Such hues. first and then heating the Solution to boiling be The colorant used for the preparation of col fore treating the methyl cellulose, or the plas ored methyl cellulose capsules may be an edible ticizer may be dissolved in a Small amount of a dye of plant or animal origin, such as carmine, compatible organic Solvent, such as ethanol, and Cudbear, or carame; or a Synthetic certified dye then intimately mixed with the methyl cellulose such as amaranth, brilliant blue F. C. F., eosin, Solution to obtain a clear, Substantially bubble erythroSine, guinea, green certified, orange I, free coating composition. pOnceau 3R, ponceau SX, Sunset yellow F. C. F. The preparation of plasticized methyl cellul and tartrazine. Combinations of these or other lose capsules is illustrated by the following ex s permissible colorants can be used to obtain meth amples: yl cellulose capsules of any desired color. Eacample 1 Eaccinaple 3 A mixture of 5.2 kg. of low-viscosity methyl 150 g. of Sorbitol, 9 g. of ponceau SX, and 1.6 cellulose, designated as 9 centipoise type, and 50 g. of brilliant blue F. C. F. are dissolved in 25 g. of monacetin is treated with 27 liters of boiling 70 liters of hot water and the resultant solution is Water and the mixture allowed to cool, where added to 5.2 kg. of 9 centipoise type methyl cel upon there is obtained a clear, bubble-free Solu lulose. This mixture is then stored at about 5° tion. Capsules prepared from this composition, C. for 24 hours to allow the methyl cellulose to by coating steel pins in accordance with the de dissolve and at the end of this period sufficient. Scribed process, were found to possess greater water is added to bring the volume to 27 liters, 2,526,688 8 The solution is well mixed and allowed to stand percent, sorbitol 2.69 percent, titanium dioxide for a few hours to permit separation of air bub 1.25 percent, and water 3 percent. bles. This coating composition is then used to prepare brown capsules in the manner described Eacample 6 above. Substantially. 150 g. of acacia (a natural gun), Capsules made in accordance with this exam 50 g. of Sorbitol, and 5 g of Carare are dis ple, when in equilibrium with air of 40 percent Solved in 27 liters of water, and the Solution is relative humidity at 20° C., had approximately heated to boiling. To the hot solution 70 g. of the following composition: methyl cellulose 93 titanium dioxide are added slowly while the mix percent, Sorbitol 3.3 percent, brilliant blue F. C. F. O ture is stirred and when the addition is complete, 0.03 percent, ponceau SX 0.2 percent, and water the mixture is added to 5 kg. of methyl cellulose, 3.5 percent. 9 centipoise type. The latter mixture is allowed Eaccingle 4 to Stand at about 5. C. for 24 hours, mixed very thoroughly to obtain a uniforn distribution of Substantially 150 g. of Sorbitol and 4.4 g. of 5 the titanium dioxide, and then stored an addi brilliant biue F. C. F. are dissolved in 27 liters tional 24 hours at about 5° C. to promote the of water and the solution is poured over 5.2 kg. Separation of air bubbles. The separation of the of methyl cellulose, 15 centipoise type, and the air bubbles can be facilitated by the addition mixture is then stored at about 5° C. for 24 hours. of a few drops of an antifoain agent Such as pine It is then thoroughly mixed to obtain a clear 20 oil or by the use of reduced preSSure as previ uniformly colored Solution and allowed to Stand Ously mentioned. Buff-colored opaque capsules, an additional 12 hours at about 5° C. to allow prepared from this bubble-free coating composi the air bubbles to separate. The cold bubble-free tion in the mainer described above, retained solution is then used to prepare blue methyl their flexibility even When dried in a vacuuin cellulose capsules according to the described 25 desiccator. When in equilibrium with air of 40 procedure. These capsules when in equilibrium percent relative humidity at 20° C. these cap With the air of 40 percent relative humidity at Sules had the approximate Cornposition: methyl 20° C. had approximately the following composi cellulose 89.75 percent, acacia, 2.69 percent, sor tion: methyl cellulose 93.75 percent, Sorbitol 2.7 bito 2.69 percent, caiannel 0.089 percent, titani percent, brilliant blue F. C. F. 0.08 percent, and un dioxide .25 percent and Water 3.5 percent. water 3.47 percent. 30 Opaque capsules prepared from methyl cellu Eacample 7 lose made by incorporating Sinal amounts of A mixture of 5.2 kg. of methyl cellulose, 9 cen insoluble and inert materials of very Srial par tipoise type, and 50 g. of monacetin is treated ticle size in the capsule-forning composition are 35 With 2 liters of boiling Water and the mixture much more. Satisfactory that those prepared is allowed to stand at about 5° C. for 24 hours. fronO geat,eatin becausebecau. the former retainetai theira A mixture of 50 g. of charcoal and 0.5 g.of flexibility Where aS Opague gelatin Capsules dis “Aerosol Oli' (100 percent) is triurated in a play a marked tendency to become brittle and Cold Enortar with about a liter of cold Water to Shatter. Moreover, for - SOrle unknoWIn reaSOn, 40 for in a SuSpension. This suspension is added the Small amount of opacity-producing material to the cold methyl cellulose solution, mixed thor expedites the theirnogelation of the cellulose Oughly and the whole maintained at about 5° C. ether on the capsule-forning pirs and thus per he mixing is continued until a uniform distri nits an increased rate of capsule production. bution of the charcoal is obtained. This mixture TWO of the most frequently used inert naterials is then allowed to Stand an additional 24 hours for the preparation of Opaque capsules are Char to obtain a Substantially bubble-free coating coal and titanium dioxide. It is necessary that composition. Froin this, dark opaque capsules the particle Size of the material added to pro are prepared in the nainner described above. duce opacity be rather Small, preferably SO that Such capsules, when in equilibrium with air of all the material will paSS through a No. 200 :50 40 percent relative humidity at 20° C., had ap Standard nesh Sieve, Uniforin distribution of proximately the following composition: methyl these insoluble materials in ninethyl cellulose Cellulose 96.2 percent, monacetin 0.92 percent, Solutions is facilitated by the use of Small charcoal 0.92 percent, “Aerosol OT' 0.0092 per amounts of natural guns or Surface tension de Cent, and water 2 percent. preSSaints, such as “AeroSol OT' (a Sodin Salt 55 By utilizing the unique gel-forming property of dioctyl SulfoSuccinate). The preparation of of methyl cellulose it has been found possible to Opaque capsules is illustrated by the folio Wing prepare capsules containing methyl cellulose as exampleS. the principal component with the admixture of Eacample 5 Small amounts of compatible cellulose derivatives About 150 g. of Sorbitol are dissolved in 27 liters 60 Such as Water-solubie hydroxyethyl cellulose, nat of water and the solution is heated to boiling. ural guns, and Synthetic water-soluble polymers 70 g. of titanium dioxide are then slowly added Such as “Carbowax 4000' (a polyethylene glycol while the mixture is stirred and the hot mixture With an average inolecular weight of about 4000). thus obtained is added to 5.2 kg. of methyl cellu The admixture of these materials to methyl lose, 9 centipoise type. The latter mixture is 65 cellulose Solutions has the effect of raising the allowed to stand for 24 hours at about 5° C., very temperature required to induce gel formation thoroughly mixed, and then allowed to stand an and therefore it will in most instances be advis other 24 hours at about 5° C. to promote separa able to use not more than 20 percent of Such tion of air bubbles. The white opaque methyl material (based on the weight of the dried cap cellulose capsules prepared fron the bubble-free 70 Sule). The preparation of capsules containing coating composition in the nanner described Such admixed materials is illustrated in the foll above were flexible and did not become brittle. lowing examples. When in equilibrium with air of 40 percent rela Eacomple 8 tive humidity at 20° C. these capsules had the 580 g. of “CarboWax 4000' are dissolved in 27 approximate composition: methyl cellulose 93 liters of boiling water and the solution thus ob 2,526,683 () tained is poured over a mixture of 58 g. of mon Sules was less than 1 percent, whereas. with gela acetin and 5.2 kg. of methyl cellulose, 15 centi tin capsules of the “run of the mill' the loss poise type. The latter mixture is allowed to was 15 percent, and Sometimes as high as 20 stand at about 5° C. for 24 hours to obtain a sub percent. - - stantially bubble-free solution suitable for coat 5 Since many medicinal preparations must be ing. Capsules are prepared from this composi prepared to contain considerably less than 8-per tion in the manner described above and by per cent moisture (the approximate lower limit of forming the dipping and gelation operations at satisfactory utility of the gelatin capsule), the about the upper temperature limits there stated. advantage of the methyl cellulose capsule is ob O vious. Thus, methyl cellulose capsules can, if Capsules so made when in equilibrium with air desired, be dried before filling them with essen of 40 percent relative humidity at 20° C. had the tially dry medicaments by exposing them to a approximate composition: methyl cellulose 87.25 dry atmosphere or by vacuum drying. A similar percent, “Carbowax 4000' 9.78 percent, monace procedure is not practical with gelatin capsules tin 0.97 percent, and water 2 percent. since, as mentioned before, gelatin capsules con Eacample 9 taining much less than 7 percent moisture are A mixture of 4.7 kg. of methyl cellulose, 9 cen too fragile for filling and handling operations. tipose type, 540 g. of water-soluble hydroxyethyl If desired, methyl cellulose capsules containing cellulose, and 160 g. of sorbitol is treated with medicaments can be stored in a container in con 27 liters of boiling water to obtain a coating 20 junction with effective drying agents, such as composition. Capsules prepared from this coat anhydrous calcium chloride, to maintain the ing composition by the process described above medicament in a substantially dry state and when in equilibrium with air of 40 percent rela prevent deterioration due to the absorption of tive humidity at 20° C. had the approximate moisture. composition: methyl cellulose 83.5 percent, wa 25 Having described my invention, what I claim ter-soluble hydroxyethyl cellulose 9.6 percent, and desire to secure by Letters Patent is: Sorbitol 2.85 percent and water 4 percent. 1. A telescoping medicinal capsule, the sub After methyl cellulose capsules have been filled Stance of which comprises a thermo-gelled film with a medicinal agent they can be sealed by of a water-soluble methyl cellulose having a applying a band of methyl cellulose to the region 30 methoxyl content of about 25 to about 35 percent where the telescoping end of the capsule cap en and an intrinsic viscosity of about 7 to about 15 circles the capsule body. This is conveniently centipoises. accomplished by extruding a cold 15 percent 2. A telescoping medicinal capsule, the sub aqueous solution of the 9 centipoise type onto stance of which comprises a thermo-gelled film this region in a thin band and Subsequently re 35 of a water-soluble methyl cellulose having a volving the capsule until the band has substan methoxyl content of about 30 percent and an tially dried. The band applied may be of the intrinsic viscosity of about 9 centipoises. same color or a distinctive color from that of the 3. A telescoping medicinal capsule, the sub body of the capsule. Other water-soluble cellu stance of which comprises a thermo-gelled film lose derivatives which can be utilized in aqueous 40 of a water-soluble methyl cellulose having a solution as capsule-sealing material are water methoxyl content of about 25 to about 35 percent soluble salts, such as sodium and ammonium and an intrinsic viscosity of about 7 to about salts, of carboxymethyl cellulose and cellulose 15 centipoises, and a compatible plasticizer there acetate-phthalate, and hydroxyethyl cellulose. for. Gelatin capsules when in equilibrium with air 4. In the process of making a telescoping of 50 percent relative humidity at 20° C. contain medicinal capsule, the steps which comprise ap about 25 percent of moisture, which causes exces plying a film of an aqueous solution of a methyl sive SWelling and renders them unsuitable for cellulose ether having a methoxyl content of mechanical filling operations. Methyl cellulose about 25 to about 35 percent and an intrinsic capsules, plasticized with 3 percent Sorbitol, un- ; viscosity of about 7 to about 15 centipoises, to der the same conditions contain 7 percent of a capsule-forming member heated above the gel moisture and remain wholly suitable for filling point of said solution to cause thermo-gelation operations. If both capsules are stored at 25 of a film of methyl cellulose on said member, and C. in an atmosphere dried with silica gel, the maintaining said film and said member continu moisture content of the gelatin capsule is re 5 ously in heated condition from the moment of duced to 7.5 percent and that of the methyl cel commencement of said thermo-gelation until the lulose capsule to 1.3 percent. The gelatin cap film is rendered self-sustaining in form. sule, however, is now very brittle and is easily 5. The method of manufacturing a telescoping shattered or broken upon handling or being medicinal capsule from a water-soluble, thermo otherwise manipulated in filling operations, gellable methyl cellulose having a methoxyl con whereas the methyl cellulose capsule still retains tent of about 25 to about 35 percent and an substantially its original flexibility and resist intrinsic viscosity of about 7 to about 15 centi ance to breakage under the usual filling condi poises, which comprises dipping into an aqueous tions. This property of the cellulose capsule is Solution of Said methyl cellulose capsule-form retained even after subsequent drying for 24 ing members heated above the gel point of said hours in vacuum at 50° C., which treatment methyl cellulose to form thereon a film of said removes practically all moisture present. methyl cellulose and supplying heat to said cap The cellulose capsules, in comparison with Sule-forming member and film thereby maintain gelatin capsules, not only have much greater uni ing said film in thermo-gelled state, and remov formity and utility under widely varying atmos ing substantially all water from said thermo pheric conditions, but are more readily produced gelled film to render said film self-sustaining. in greater uniformity. For example, in machine 6. The method of manufacturing a telescoping filling operations with cellulose capsules, accept medicinal capsule from a water-soluble methyl ing all capsules routinely produced in any given cellulose having a methoxyl content of about 25 period, the largest number of unsatisfactory cap 5 to about 35 percent and an intrinsic viscosity of 2,526,688 1. 12 about 7 to about 15 centipoises, said method UNITED STATES PATENTS comprising dipping capsule-forming members in an aqueous solution of said methyl cellulose, Said Number Name Date members being heated above the gel point of Said 730,643 Hance ------June 9, 1903 methyl cellulose and being of a size and Shape 1730,377 Anderson ------Feb. 26, 1929 to permit formation thereon of complementary 1861,047 Colton ------May 31, 1932 cap and body portions of said capsules, with 2,031,233 StillWell ------Feb. 18, 1936 drawing said members from the aqueous solution 2,160,782 Magsberg ------May 30, 1939 and rotating said members and partially thermo 2,215,562 Ogilby ------Sept. 24, 1940 gelled film of methyl cellulose thereon to cause 0. 2,216,045. Powers et al. ------Sept. 24, 1940 formation of a uniform thermo-gelled film on 2,251,109. Bratring ------July 29, 1941 Said members and maintaining Said members and 2,275,154 Merrill ------Mar. 3, 1942 said thermo-gelled film at a temperature above 2,304,676. Bratring ------Dec. 8, 1942 the gel point of Said cellulose derivative, thereby 2,339,114 Scherer ------. Jan. 11, 1944 2,349,430 Hiatt ------May 23, 1944 causing evaporation of substantially all moisture 5 from Said film and rendering said film in Self OTHER REFERENCES Supporting condition. Deakers: Drug and Cosmetic Industry, Feb. HUBERT W. MURPHY. 1941, vol. 48, page 152 (167-90). REFERENCES CTED 20 The following references are of record in the file of this patent: