US 3048526 A
Description (OCR text may contain errors)
1962 c. L. BOSWELL 3,048,526
MEDICINAL TABLET Filed Aug. 4, 1958 /l//ll//l//l//l/l/ 22 I z OT 5 NV.
!e e& 14 13 12 3,048 526 Fatented Aug. 7, 1962 &948,526 MEDECINAL TABLET Charles L. Bosweil, Lincoln, Nebr., assignor to The Wander Company, Chicago, ill., a corporation of Deiaware Filed Ang. 4, 1953, Ser. No. '752,768 4 Ciaims. (Cl. 167--82) This invention relates to a novel and improved me dicinal tablet and more particularly to a tablet of the type containing substantially segregated quantities of the same or different ingredients.
lt is frequently desired to provide medicinal or pharmaceutical compositions in solid dosage unit form wherein each dosage unit contains segregated quantities of the ingredients of the preparation. For example, one type ot' medicinal tablet or pill which is useful for delayed action or multiple dosage medication is the so-called tablet-wi-thin-a-tablet or double tablet Construction which consists of an innermost core tablet, a thin enteric coating around the core tablet, and an outermost shell or layer. Upon oral administration, the medicinal ingredients in the outermost shell are readily assimilated in the gastro-intestinal tract to pro-vide immediate therapy. After a predetermined period of time, the gastrointestinal fluids dissolve the enteric coatin on the inner core portion of the tablet and the ingredients of the latter are. then available for assimilation. Thus, 'a sustained or delayed action eifect is realized which is equivalent to the result which would be obtained by repeated administration of conventional tablets over a period of time. Another type of medicinal tab-let which is also employed in certain instances is the so-called layered tablet which consists of two or more superimposed layers of medicinal ingredients compressed together to form a unitary tablet. A layered or multiple compressed tablet of this type is used primarily in sit-uations where it is necessary to separate or segregate two different pharmaceutical ingredients which are to be administered at the same time but which have an adverse effect upon each other so that they cannot be intimately commingled beforehand. For example, an acidic medicinal ingredient may have a detrimental ettect on a companion ingredient which is susceptible to acid action.
However, both the tablet-within-a tablet and the layered tablet constructions have serious limitations. For example, in the tablet-within-a-tablet the inherent geometry of the Construction is such that the quantity of mea that the tablet-within-a-tablet Construction avoids this dicinal ingredient or ingredients forming the outer shell of the tablet is always substantially greater than the quantity of material forming the inner core of the table-t. In a typical instance, the dosage content in the outer shell may be as much as twice as great as the dosage content of the inner core tablet. Moreover, in the tablet-withina-tablet Construction it is necessarily the outer shell portion of the tablet which is first released and assimilated in the gastrointestinal traot. It will readily be understood that these limitations may frequently restrict the scope and utility of this tablet form.
In the layered tablet, the chief disadvantages are an undesirable merging of the ingredients at the interface between the layers and also a poor degree of control over the relative quantities of the ingredients in the respective layers. These disadvantages are occasioned by the necessity of producing a layered tablet in a single compression step so as to o btain a unitary tablet having the required mechanical strength and coherence. Generally speaking, the layered tablet is formed 'by successively introducng into a die cavity measured amounts of the respective granulated ingredients so as to form two or more superirnposed layers of the several ingredients. After the die cavity is filled, a plunger compresses latter difliculty because the inner core 'portion is preformed in a first tabletting or compression operation and thereafter the outer shell is compressed around the preformed core so that there is 'no merging under pressure of the separate granulations.
In View of the foregoing discussion, it will be seen that there is a decided need for an improved tablet form which afiords the advantages of both the tablet-within-atablet and the layered tablet constructions without the disadvantages inherent in each of these known therapeutic forms.
Accor-dingly, a primary object of the invention is to provide a novel and improved form of medicinal tablet of the type adapted to contain substantially segregated quantities of ingredients.
A further object of the invention is to provide a novel and improved medicinal tablet of the aforementioned type which combines the advantages of the prior `art tablet forms without the disadvantages thereof.
Another object of the invention is to provide a novel and improved medicinal tablet which is particularly adapted to contain incompatible ingredents which must be protected from each other.
' for production on modern high speed taljletting equipment.
Other objects and advantages of the invention will become apparent from the subsequent detailed description taken in conjunction with the accompanying drawing, wherein:
FIG. l is a plan view of a tablet comprising one specific embodiment of the present invention;
FIG. 2 is an edge view 'of the tablet shown in FIG. 1;
FIG. 3 is a transverse sectional view as seen along the line 3--3 of FIG. 1;
FIG. 4 is a view similar to FIG. 3 but showing a modilied form of the invention;
FIG. 5 is a sectional view similar to FIG.. 3 but showing another embodiment of the invention; and
EIG. 6 is a sectional View of still another emb odiment of the invention Referring first to FIGS. 1 to 3 and 5, a tablet 10 is shown of a conventional overall configuration and having a main body portion 11 with an outwardly opening cavity or recess i?. in one side thereof and an inlay portion 13 contained in the `cavity 12 so as to form a unitary tablet construction with the main body portion 11. A modification is shown in FIG. 5 wherein the main body portion 11' extends radially inwardly to a slight extent around the marginal edge of the opening of the cavity 12 in the side of the tablet so as to provide `an overlying peripheral lip portion 14- for retaining and mechanically interlocking with the inlay tablet portion 13. In manufacturing the tablet, the inlay portion 13 is first compressed in a tabletting machine in the usual manner to provide a compressed preform. This preform is then subjected to a further tabletting operation of a conventional character wherein another granulation is compressed around the preform 13 to provide the surrounding body portion lili.
Inasmuch as both the inlay portion 13 and the main body portion 11 of the tablet are formed by independent compression or tabletting steps, it will be understood that highly accurate control can be exercised over the quantities of ingredients which form the two parts of the tablet. Furtherrnore, since both the inlay portion 13 and the main body portion 11 have exposed outer surfaces, it can readily be arranged to permit either the portion il or the portion 13 to be released first in the gastrointestinal tract with any desired degree of time delay in the release or assirnilaton of the other portion of the tablet. in the present emhodiment as seen in FIG. 3, dilferential releasability between the portions 11 and 13 of the tablet is realized by using a coated granulation for one portion and an uncoated granulation for the other portion of the tablet. For example, assuming that the inlay portion 13 comprisng the smaller dosage of ingredients is to be assrnilated first, the portion 13 may be preformed from an uncoated granulation so that this portion is immediately dissolved in the gastrointestinal tract. However, the main body portion 11 of the tablet comprising a larger dosage of the same ingredients may be formulated as coated granulation in which each granular particle has a time delay or enteric coating designed to resist assimilation in the gastrointestinal fluids. Such coated granulations are well known in the art and require no detailed description. It will also be understood that the same technique of coated and uncoated granulations for the inlay and main body portions of the tablet may be utilized where the tablet portions contain different medicinal ingredients which have an adverse effect on each other and must, therefore, be protected from each other. Also, it will be appreciated that the larger portion 11 may be formed from an uncoated granulation so as to be assimilated first and the smaller inlay portion 13 may be formed from a coated granulation for delayed assimilation thereof.
In FIG. 4, a modification of the invention is shown wherein segregaton of the inlay and main body portions of the tablet, for purposes of time delay or positive separation of incompatible ingredients, is realized without the necessity of employing `a coated granulation for one of the tablet portions. Thus, the preformed inlay portion of the tablet, designated at 16, may be formulated from an uncoated granulatior and is then surrounded by a thin enteric coating or envelope 17 of a conventional character. The main body portion is desgnated at 18 and may also consist of an uncoated granulation which is conipressed around the enteric coated inlay portion lid-17. In this modification of the invention the main body portion 18 of the tablet is first released and assimilated in the gastrointestinal tract while the enteric coating 17 protects the inlay portion 16 for a predetermined period of time so as to provide time delayed or sustained medication.
Of course, in addition to the provision of a separate enteric coating or envelope for the inlay portion of the tablet as illustrated in FIG. 4, the particles of the granulation in either or both portions of the tablet may be coated to any desired degree so 'as to provide a further degree of control over the time release feature and positive segregation feature of the tablet construction.
Various enteric coating materials are well known to those skilled in the art and extended discussion thereof is, therefore, unnecessary. :For example, the more common enterc coating materials include cellulose acetate phthalate, tolu balsam, carnauba wax, alcoholic shellac solutions, hydrogenated fats, etc. It will he understood that the same general types of enteric coating materials may be used for coating either an entire compressed tablet portion or the individual particles of a granulation prior to compression.
In FG. 6, a further modification of the invention is shown comprisng a tablet having a main body portion and two separate inlay portions at opposite sides of the tablet. Thus, the two oppositely disposed inlay portions are designated at 19 and Zi wit i the main body portion being designated at 22. It will be noted that the inlay portons 19' and 21 have exposed surfaces at opposite sides of the tablet and that the material comprising the main body portion 22. extends around the peripheral edges of the inlay portions and is also disposed as a thin layer between the inlay portons so that the latter are completely segregated from' each other. As will readily be understood, the previously discussed advantages of the invention are extended even further by means of the double inlay arrangement. For example, the inlay portions 19 and 21 may conprise the same or dierent pharmaceutical compositions and they may be `coated or uncoated so as to provide any desired sequence of delayed or concurrent release between the respective portions 19, Zi, and'ZZ of the tablet in accordance with the means heretofore described.
Merely by way of illustration, the following specific examples represent typical inlay tablets which may be made in accordance with the present invention.
Example I An appetite depressant tablet is formulated in the manner shown in FIGS. 1-3. In the outer layer the particles of the granulation are enteric coated to provide slow release over a period of ten to twelve hours. The inlay portion is formed from an uncoated readily disintegratable granulation for immediate therapeutic eifectiveness.
The formula for the outer layer is as fcllows:
d-Amphetamine sulfate mg 10 Amobarbital rng 30 Excipients q.s. Enteric coating solution for coatng granulation q.s.
The formula for the inlay portion is as follows:
d-Amphetamine sulfate "mg" 5 Amobarbital mg 15 Excipients q.s. Standard granulating solution q.s.
Example H An oral decongestant tablet is formulated as in Example I with the outer layer comprising a coated granulatior and the inlay portion an uncoated granulation.
The formula for the outer layer is as follows:
with an enteric coating or envelope around the inlay portion. Thus, the outer layer is promptly disintegratable for immediate hypnotic efect and the inlay portion begins to disintegrate after three to four hours to maintain or continue the desired effect.
Pharmaceutical glaze shellac granulating solution q.s. Enteric eoating materials for coating inlay portion of tablet q.s.
Although in the illustrated embodiments the invention has been described in connection with tablets having the conventional round shape, it is to be understood that the features of the invention may also be utilized in tablets of different and less conventional shape such as triangular, rectangular, or capsule shaped tablets.
As described above, it will be seen that the invention provides a novel tablet Construction which provides wide flexibility in the compositing of segregated quantities of medicinal ingredients either for purposes of time delayed medication or protection of inconpatible ingredients from each other. At the same time, the tablet form permits of positive separation of the segregated areas with accurate control over the relative amounts of the several portions of the tablet. The -final tablet is readily adapted for varying relative dosages of difierent ingredients and varying orders of releasability depending upon the therapeutic effects desired. Moreover, in most cases conventional tabletting and compression coating machines will require only relatively minor modifications to adapt them to the production of inlay tablets as herein described, particularly with respect to FIGS. 1-4. Finally, the inlay construction of the tablet aiords a unique and distinctive appearance, particularly if the inlay portion of the tablet is of a eontrasting color with respect to the surrounding body portion thereby contributing significant advantages to the tablet constructon both during production and merchandising. For example, during production the presence of an exposed inlay portion of contrasting color with the remainder of the tablet provides instant visual proof that a complete tablet has been made and thereby greatly facilitates inspection of the final product before ackaging and shippng.
Although the invention has been illustrated and described with respect to certain specific embodiments thereof, it is to be understood that various modifications and alternatives may be resorted to without depart'ng from the scope of the invention as defined in the appended claims. r
1. A method of making an oral dosage tablet form which comprises; compressing a finely divided medicinal ingredient portion to form a compressed tablet inlay portion having smaller dimensions than the desired finished tablet form, positioning the preformed compressed tablet inlay portion in contact with a second finely divided medicinal ingredient portion, compressing said second medicinal ingredient portion about only a part of said compressed tablet inlay portion to form a compressed main body portion and exposing only a single surface of said compressed tablet inlay portion on the outer surface of the finished tablet form, and said single surface lying in substantially a common plane with contiguous portions of said compressed main body portion.
2. An oral dosage tablet form comprising; a compressed tablet inlay portion of a finely divided medicinal ingredient portion with said compressed tablet inlay portion having smaller dimensions :than the desired finished tablet, and a compressed main body portion comprising a second medicinal ingredient portion compressed about only a part of said tablet inlay portion with only a single surface of said compressed tablet inlay portion exposed on the outer surface of the finished tablet form and said single surface lying substantially in a common plane with contiguous portions of said compressed main body portion, and said oral dosage tablet form being made by compressing the first mentioned said finely divided medicinal ingredient portion to form said compressed tablet inlay portion, positioning said compressed tablet inlay portion in contact with said second finely divided medicinal ingredient portion, compressing said second medicinal ingredient portion about only a part of said compressed tablet inlay portion to form said compressed main body portion and expose only said single surface of said compressed tablet inlay portion on the outer surface of the finished tablet form with said single surface lying in substantially a common plane with contiguous portions of said main body portion.
3. An oral dosage tablet form as defined in claim 2, wherein said finished tablet form has a second compressed tablet inlay portion disposed therein with said second compressed tablet inlay portion having only a single surface thereof'exposed on the outer surface of said finished tablet form.
4. A method of treating a human body with a drug which comprises; administerng to a human host an oral dosage tablet form comprising a compressed tablet inlay portion of a finely divided medicinal ingredient portion with said compressed tablet inlay portion having smaller dimensions than the desired finished tablet form, and a compressed main body portion comprising a second medicinal ingredient portion compressed about only a part of said compressed tablet inlay portion With a single surface of said tablet inlay portion exposed on the outer surface of said finished tablet form, and said single surface lying substantially in a common plane with contiguous portions of said main body portion.
References Cited in the file of this patent UNITED STATES PATENTS 109,677 Seitz Nov. 29, 1870 701,438 Whyte June 3, 1902 1,267,320 Fries May 21, 1918 `1,5 16,398 McDowell Nov. 3, 1924 1,855,- Jones Apr. 19, 1932 2,312,381 Bi'ckenheuser Mar. 2, 1943 '2,809,917 Hermelin Oct. 15, 1957 2,951,792 Swintosky Sept. 6, 1960 2,957,804 Shuyler Oct. 25, 1960 2,987,445 Levesque June 6, 1961 2,991,226 Millar et a-l. July 4, 1961 2,966,431 Barry Aug; 15, 1961 FOREIGN PATENTS 1,651 Great Britain 1891 OTHER REFERENCES Drug and Cosmetic Industry, vol. 7 8, No. 1, article Press-Coated and Multi-Layer Tablets, by Tsevdos, January 1956, pages 38, 39, 40, 113 114.