Rapidly dissoluble medicinal dosage unit and method of manufacture

A melt spinnable carrier agent such as sugar is combined with a medicament then converted into fiber form by melt spinning with "cotton candy" fabricating equipment. The as-spun product is converted to compacted individual dosage units. For certain medicaments a binding agent is added to the carrier agent. Examples are presented for oral administration, topical application, systemic and non-systemic, intravenous and intra-muscular infusion via multicameral containers. All applications utilize the extraordinarily rapid entry into solution upon contact with a solvent.

The present invention relates to a medicinal dosage unit, e.g., a tablet or 
the like, and to a method of producing the same. More particularly, it 
relates to a non-liquid dosage unit that is rapidly dissoluble for use in 
administering a medicinal substance either orally, topically or by 
infusion. 
It is well known that a substance placed in the oral cavity of an animal, 
if absorbable by body tissue, is absorbed much more effectively than if 
the same substance were introduced directly into the stomach or digestive 
tract. Therefore, many medicinal substances are administered either 
lingually, sublingually or buccally. However, some medicinal substances, 
while for the sake of effectiveness and economy would best be administered 
lingually, sublingually or buccally, cannot be so administered because of 
an undesirable taste attribute and/or a slowness to dissolve. 
In pediatric practice, when oral administration is desired, there exists 
the additional problem of insuring that the medication remains in the 
mouth and is swallowed and not expelled even if there is no antagonistic 
taste characteristic. In animal husbandry much the same problem exists 
regardless of taste. 
Consequently, there is a great need for some form by which medication can 
be administered orally and be rapidly dissolved and absorbed with 
sufficient speed as to avoid significantly the foregoing problems. Others 
have recognized and worked on the problem. In Gregory et al. U.S. Pat. No. 
4,371,516 issued Feb. 1, 1983, there is described a shaped article or 
pharmaceutical dosage form carrying a pharmaceutical in which the article 
comprises an open matrix network of carrier material which is prepared by 
subliming solvent from a composition comprising the pharmaceutical and a 
solution of the carrier material in a solvent, e.g., a hydrolyzed gelatin 
solution. According to the patent some embodiments dissolve in the saliva 
of the mouth in one or two seconds. The patent describes the open matrix 
network as being similar in structure to a solid foam. Unfortunately, the 
Gregory et al. product is still too slow to dissolve for many purposes and 
has other drawbacks. 
Certain drugs in solid or tablet form or the like are intended to be 
ingested and are therefore taken with water or other liquid. Among such 
drugs, the therapeutic value is a function of the speed with which they 
dissolve. While some are deliberately designed with a delayed action, 
others should dissolve as rapidly as possible. Ideally, the medicament 
should dissolve so rapidly that when taken with a liquid it is swallowed 
practically as a solution. 
There are various forms for administering a medicament topically. Salves 
and ointments immediately come to mind. However, there are various 
situations where the medicament is required only when the dermal area 
becomes moist such as when a wound bleeds or produces a secretion. Also, 
release of the active agent from a salve or ointment is comparatively slow 
whereas there are occasions when rapid delivery is desirable. Moreover, 
salves and ointments tend to be messy, the major constituent is the 
vehicle and not the active agent, and they are difficult if not impossible 
to spread uniformly over the skin. The amount of material and therefore 
the concentration of medicament is greatest at the point of direct 
application, and then, as with a snowplow, gradually thins out as it is 
spread from the point of application over the surface of the skin. 
In another area, packaging of generally unstable dry medicaments for 
production of intravenous solutions currently involves use of a costly 
production technique whereby the medicament is lyophilized using a freeze 
drying procedure. A bicameral container is then employed to isolate the 
dry freeze dried pharmaceutical from a solvent such as distilled water or 
the like, until immediately prior to infusion. Immediate sediment-free 
dissolution in the solvent is required. 
SUMMARY OF THE PRESENT INVENTION 
It is an object of the present invention to provide a rapidly dissoluble 
medicinal dosage unit that is more rapidly dissolved and absorbed and is 
more palatable than anything known heretofore. 
It is another object of the present invention to provide a rapidly 
dissoluble medicinal dosage unit of controllable potency that is 
relatively inexpensive to produce. 
Another object is to provide a dry medicinal form that is less expensive to 
manufacture than freeze dried product yet dissolves at least as rapidly if 
not more rapidly than lyophilized material. 
Other objects will occur to those skilled in the subject art after reading 
the following detailed description. 
In accordance with one aspect of the present invention there is provided a 
spun fibrous pharmaceutical composition comprising a mass of spun fibers 
of a readily water-soluble material capable of being spun into fibers and 
a medicament distributed on or incorporated in said fibrous mass. 
In accordance with another aspect of the present invention there is 
provided a system for topical transdermal delivery of a medicament 
comprising a wafer containing a mass of fibers, and means for securing 
said wafer in contact with a dermal area to be treated, said mass of 
fibers comprising a soluble fiber forming ingredient and a medicament 
where at least said fiber forming ingredient has been spun into fibers, 
and in said fiber form said ingredient has a solubility characteristic 
corresponding to that of spun sugar fibers in water. 
In accordance with a further aspect of the present invention a bicameral 
container for intravenous administration is provided with a first 
compartment containing a pharmaceutically acceptable solvent, and a second 
compartment containing a spun fibrous pharmaceutical composition 
comprising a mass of spun fibers of a readily water-soluble material 
capable of being spun into fibers and a medicament distributed on or 
incorporated in said fibrous mass. 
Yet, in accordance with another aspect of the present invention there is 
provided a method for preparing a rapidly dissoluble medicinal dosage unit 
for administering medication orally, comprising in combination the steps 
of combining a medicament with a melt spinnable compatible carrier agent 
to provide an intermediate product, and producing a mass of medicament 
bearing fibers by melt spinning said intermediate product. 
The invention will be better understood after reading the following 
detailed description of the presently preferred embodiments thereof.

DETAILED DESCRIPTION OF THE 
PRESENTLY PREFERRED EMBODIMENTS 
The spun sugar fiber confection of sucrose, commonly referred to as cotton 
candy, is well known to children and most adults. Also, it should be 
obvious to all who have eaten cotton candy that the sucrose sugar 
literally melts in the mouth and seems very quickly to disappear to 
nothing. In its spun form the sugar is very fragile. However, the sugar 
fibers can be compacted to form a sheet-like body that can be handled more 
readily. Two patents describe methods for producing compacted confections 
from spun sugar, namely Warning et al. U.S. Pat. No. 3,930,043 and Oiso et 
al. U.S. Pat. No. 4,526,525. 
In U.S. Pat. No. 4,496,592 of Kuwahara et al. a chewing gum is described 
that is produced in the form of composite fibers by fiberizing a sugar 
and/or a candy and a chewing gum base or composition through a fiberizing 
section, such as a rotating cylinder, of a candy floss making machine. 
Of the foregoing patents, none considers or suggests the possibility of 
using any form of fibrous sugar or cotton candy as a carrier for a 
medicament, a pharmaceutical component. 
With that as background, it has been discovered that many pharmaceutical 
compounds useful as medicaments can, in fact, be combined with a spinnable 
readily dissoluble material, such as sugar, in such manner that the 
resultant composition can still be spun into fiber form by melt spinning 
and without deteriorating the medicament or reducing its effectiveness. 
Generally speaking, the particular sugar or other material used as a 
carrier agent should have a melting point that is a safe distance below 
that temperature at which the medicament might decompose or otherwise 
break down, but not necessarily below the melting point of the medicament. 
Subject to that requirement, any material, such as sugar or a sugar-like 
substance that can be melt spun to produce a fibrous structure which 
substance dissolves rapidly in water, the saliva of the mouth, or other 
sera, is non-toxic, and is compatible with the particular medicament, is 
suitable in the practice of the present invention. 
From a dosage standpoint, it has also been discovered that the method to be 
described is able to produce with acceptable reliability consistent and 
uniform distribution of the medicament throughout the carrier agent. This 
is essential for medicinal use where the quantity of effective medicament 
in each dosage unit should be known or ascertainable. 
The present invention can best be explained by considering a series of 
examples. First, a pediatric formulation was prepared using acetaminophen 
(abbreviated APAP). The objective was to provide a product containing 60 
mg acetaminophen per gram of product. A thick slurry of acetaminophen was 
prepared consisting of 60-70% w/v acetaminophen in isopropyl alcohol. A 
measured quantity of common granular sugar was added to the slurry and the 
sugar granules were coated uniformly with the slurry. The coated sugar 
granules were then dried for 3-4 hours at a temperature that varied 
between 45.degree. C. and 65.degree. C. (113.degree. F.-149.degree. F.), 
the target control temperature being about 50.degree. C. (122.degree. F.). 
Next, using conventional "cotton candy" spinning equipment, operating at a 
melt temperature that ranged between 90.degree. C. and 130.degree. C. 
(194.degree. F.-266.degree. F.), the coated granules were converted to 
spun fiber form having the consistency and physical appearance of cotton 
candy. In order to determine the uniformity of the resultant product, 
three different portions of the fibrous product were sampled from 
different sections of the batch and each portion was analyzed to determine 
the acetaminophen content. The results are in Table I. 
TABLE I 
______________________________________ 
Sample mg of Acetaminophen per 
Percent Acetaminophen 
No. gram of fibrous product 
per dosage unit 
______________________________________ 
1 54.6 mg 91.0% 
2 57.0 mg 95.0% 
3 52.2 mg 87.0% 
______________________________________ 
The results indicate that the medicament has been uniformly distributed. 
The samples were also tested for taste and were found to be slightly 
bitter but in the acceptable range. 
Next, a formulation for animal husbandry was attempted using 
diethylcarbamazine citrate (abbreviated DCM citrate) for which the target 
dosage was 200 mg per gram of fibrous product. This medicament is useful 
as an anthelmintic. 
A thick slurry of the medicament was prepared with 60% w/v of 
diethylcarbamazine citrate in isopropyl alcohol. Sugar granules were added 
and coated with the slurry and then dried for 3-4 hours at a temperature 
that varied between 45.degree. C. and 65.degree. C. (113.degree. 
F.-149.degree. F.), the target control temperature being about 50.degree. 
C. (122.degree. F.). Upon drying it was observed that the medicament did 
not adhere effectively to the sugar granules which could result in lack of 
uniformity in the final product. 
The isopropyl alcohol (abbreviated (IPA) was then replaced with purified 
water but it was impossible to obtain completely dry granules. 
Finally, good adhesion was obtained by adding a promoter of adhesion to the 
isopropyl alcohol before mixing with the drug. Specifically, a 2-3% 
solution by weight of polyvinylpyrrolidone (abbreviated PVP) in isopropyl 
alcohol was prepared, and this solution was used to prepare a thick slurry 
with diethylcarbamazine citrate, again incorporating about 60% w/v of the 
medicament in solution. A measured quantity of common granular sugar was 
then coated with the slurry and dried for 1-3 hours at a temperature 
similar to that used with the prior examples. This product was then spun 
in the "cotton candy" apparatus to produce an end product from which 
samples were taken and assayed using spectrophotometric procedures. The 
results were presented in Table II. 
TABLE II 
______________________________________ 
mg of diethylcarbamazine 
Percent of 
Sample citrate per gram of 
diethylcarbamazine 
No. fibrous product citrate per dosage unit 
______________________________________ 
1 174 mg 87% 
2 166 mg 83% 
3 188 mg 94% 
______________________________________ 
While PVP is specifically mentioned as an adhesion promoter, it is intended 
merely as an example of a non-toxic, compatible, pharmaceutically 
acceptable, ingestible film former. 
The results of additional tests to produce a number of medicaments (drugs) 
in fiber form are tabulated below in Table III. In the column headed 
"DRUG", the letters identify the drug in accordance with the following 
list while the numbers indicate the weight in grams. 
A=acetaminophen (APAP) 
C=chlorpheniramine maleate (CPM) 
D=diethylcarbamazine citrate (DCM) 
M=metoclopramide hydrochloride 
P=phenylpropanolamine (PPA) 
Z=mucopolysaccharide 
In the column headed "SUGAR" the numbers indicate the weight in grams of 
common table sugar, i.e., granulated sucrose, unless noted otherwise. 
Unless otherwise noted, the "SOLVENT" was isopropyl alcohol (IPA) in 
approximately the volume indicated in milliliters. Drying temperatures are 
approximate and given in degrees Celsius, and unless indicated otherwise, 
was accomplished at approximately 40.degree. C. for 1/2 hour. Unless a 
different procedure is mentioned under "REMARK", the drug was dissolved in 
the solvent to produce a slurry to which the sugar was added and coated 
uniformly. The coated sugar was then dried and spun into fibers. 
TABLE III 
__________________________________________________________________________ 
TEST DRUG SUGAR SOLVENT 
NO. (gms) (gms) (ml) DRYING REMARK 
__________________________________________________________________________ 
1 A-8 100 12 
2 D-10 50 15 
3 D-10 50 H.sub.2 O - 5 
45-60.degree. C. 
Never 
obtained 
dry mass 
4 D-10 50 0.4 g PVP 
40-45.degree. C. 
in 15 ml 
for 1/2 hr. 
IPA 
5 A-5 50 12 
6 Coated 
50 12 
A-5 
7 A-5 50 IPA-12 + 
4 drops of 
peppermint 
oil 
8 D-10 50 15 
9 A-5 50 15 
micron- 
ized 
10 M-1.182 
100 10 
11 A-8 100 12 
12 C-0.4 100 10 
13 P-3.75 + 
295.65 
20 
C-0.6 
14 C-0.6 299.4 20 
15 Z-5 95 Mixed drug and 
sugar and spun 
fibers 
16 C-0.4 99.6 10 
__________________________________________________________________________ 
The spinning process for producing "cotton candy" is a melt extrusion 
process in which the stock material is melted and forced through 
spinnerettes. The conventional equipment uses a rotating spinning head 
surrounded by a bowl into which the fibers are spun. Using a medicated 
sugar formulation, medicated fibers are obtained. In order to convert the 
cottonlike mass to a form that can be packaged and handled, the aspun 
product generally must be compacted to produce a compact body being 
careful not to squeeze too much. It is important that the final dosage 
form retains its fibrous character so that it will dissolve rapidly in the 
saliva of the mouth or other solvent. At present, it is believed desirable 
for "tablet" production to reduce the initial spun volume by approximately 
two thirds or until the threshold is reached beyond which the fibers would 
fracture or coalesce. Preferably, the material is compacted as much as 
possible to produce a wafer-like structure while avoiding fracturing of 
the fibers or loss of the discrete fibrous identity. However, it will 
become apparent from the ensuing description that there will be occasions 
when a lesser degree of compaction or even no compaction is desirable. 
When compaction is employed, it preferably is performed to produce a body 
with an enclosed volume that is at least 30% less than the as-spun 
enclosed volume. 
Various procedures can be followed to produce discrete dosage units. It is 
assumed that the medicament is uniformly distributed on or incorporated in 
the fibrous mass. A measured weight or volume of the as-spun product can 
be compacted as discrete units and sealed within a moisture proof package 
or wrapper. Alternatively, the as-spun product can be compacted on a 
continuous basis to produce a sheet or web which is subsequently 
subdivided to produce the individual units. These units can be packaged, 
preferably individually, using any known and appropriate technique that 
will exclude moisture since, depending upon the sugar, the fiber products 
have varying degrees of stability under normal humidity conditions. 
Compaction of the fibrous mass can be accomplished before or during 
packaging or both. Partial compaction can be achieved between rollers or 
the like, with the resultant fibrous web entering between layers of 
packaging film. Then platens or the like can be applied to seal the 
individual units with squeezing of the film layers further compacting the 
fibers. The units can be severed either before, after or during the 
sealing step. Ultrasonic devices can be used to accomplish sealing and 
severing, or die cutters can be employed. It is contemplated that any 
suitable packaging technology can be employed so long as the packaging 
material excludes moisture and does not compress the fibrous mass to the 
point of destroying its fibrous structure. 
At present, it is preferred to use a foil laminate material and allow the 
fiber product to cool to ambient temperature under controlled dry 
conditions before encapsulating in a foil laminate pouch. It has been 
found that attempts to seal the fiber product while still warm were 
unsatisfactory because of the tendency for moisture in the atmosphere to 
condense on the cool foil and remain trapped within the pouch to cause 
deterioration of the fiber structure. An acceptable packaging laminate is 
a mylar-foil laminate. 
Any material capable of being spun into fibers and readily dissoluble in 
water may be used as the carrier agent. Presently preferred materials are 
sugars such as sucrose, fructose, dextrose, mannitol, sorbitol, flucose, 
lactose and maltose; and water soluble cellulosic materials such as methyl 
cellulose, ethyl cellulose, hydroxy methyl or ethyl cellulose and alkali 
metal salts of carboxy methyl cellulose. Particularly useful, for example, 
is a mixture of sucrose and lactose, in which the useful ratio of sucrose 
to lactose may vary from 90:10 to 50:50. Lactose is a preferred sugar by 
reason of its relative stability under humid conditions. However, lactose 
is less sweet than sucrose and it is generally desirable to combine it 
with a sweetener. 
Additives, such as coloring agents, flavoring agents, artificial 
sweeteners, having acceptable food and drug approval, and which are 
compatible with the carrier agent and medicament, can be included in the 
product that is melt extruded. For example, lactose has been spun 
successfully after having been combined with saccharin and aspartane. 
While the components discussed herein have been produced by coating the 
granules of the carrier agent with the medicament, it is contemplated that 
the medicament can be distributed within the carrier by co-crystallization 
from a solution containing both the carrier agent and the medicament, or 
by any other known technique. 
There are a number of drugs presently available which are given 
intravenously but which are unstable for storage in a liquid state. In 
order to package and supply such drugs in convenient form, bicameral or 
multicameral containers are used with the dry drug constituent in one 
compartment and a solvent such as distilled water or saline solution in 
another compartment isolated from the first compartment until, immediately 
prior to infusion, an intercompartmental seal is pierced or broken. For 
obvious reasons the FDA has stringent guidelines as to particulate residue 
that might remain undissolved at time of infusion and create a risk if 
such residue were to enter the veins or muscle mass of a patient. 
Consequently, current practice is to subject the drug to an expensive and 
difficult freeze drying or lyophilization process which produces particles 
with sponge-like pores fostering rapid entry into solution. Typical drugs 
presently packaged in this fashion are corticosteroids such as 
methylprednisolone sodium succinate sold under the "Solu-Medrol" brand 
name by The Upjohn Company, antibiotics such as cefazolin sodium sold 
under the "Kefzol" brand name by Eli Lilly and Company, vitamins such as B 
vitamins sold under the "Solu-B" brand name by The Upjohn Company, and 
numerous drug/parenteral-fluid preparations packaged by Baxter Travenol. 
It has been discovered, however, that producing the drugs in fiber form as 
described in this application results in a dry quantum of the drug that is 
easier to manufacture, much less costly to produce, and that functions in 
the bicameral or multicameral environment as well if not better than 
lyophilized material. Since the fibrous product is hermetically sealed in 
a glass vial or other container until use, it has adequate shelf life. 
In order to test this concept four glass vials of methylprednisolone sodium 
succinate produced by Abbott Pharmaceuticals, Inc. under its "A-Methapred" 
trademark, and containing 125 mg/vial, were emptied and the solid contents 
(the liquid diluent was discarded) were mixed with 20 grams of crystalline 
Lactose USP (hydrous), and granulated with isopropanol. The resulting 
material was dried on paper toweling and spun using commercial cotton 
candy apparatus at the high heat setting. A quantity of the resultant 
floss was rolled into a mass weighing approximately 0.5 gram and capable 
of being placed in the Abbott Pharmaceutical, Inc. vial. Thus, the dosage 
contained 0.0125 gm of medicament. This test obviously only establishes 
the feasibility of the concept and is not intended to produce an 
injectable product. For commercial production the compounding should be 
accomplished in a clean-room environment with the use of highly refined 
sugar and drug. In order to duplciate the original dosage level, either 5 
grams of fiber material would have to be included in the vial or 10 times 
the concentration of drug would have to be used when compounding. It 
should be understood that in all cases appropriate steps must be taken to 
establish and insure sterility of the product. 
Additional experiments have been performed with other drugs. Tablets of 
"Dramamine" (dimenhydrinate) of 50 mg concentration were crushed in a 
mortar and pestle, 8 tablets being granulated with 20 grams of a berry 
flavored floss sugar using isopropanol. The product was air dried 
overnight and spun using commercial cotton candy apparatus at a medium 
heat setting. The resultant material was packaged in various packaging 
material in 1 gram doses to test shelf life. 
The experiment was repeated using 10 tablets of chlorpheniramine maleate, 4 
mg/tablet, which were granulated with 20 grams of berry flavored floss 
sugar using isopropanol. The product was air dried overnight and spun 
using the commercial cotton candy apparatus at a medium heat setting. 
Doses of 1 gm each were packed in various pouches and sealed. 
A sinus preparation consisting of acetaminophen, phenylpropanolamine and 
phenyltoloxamine, and marketed by H. L. Moore Co. under the brand name of 
"Sinu-Prep", was used, 8 tablets being crushed and granulated with 20 
grams of berry flavored floss sugar using isopropanol. The granulation was 
dried overnight and spun utilizing commercial cotton candy apparatus. 
Pouches were filled and segregated for testing of longevity. 
The result of this series of packaging tests revealed that a sucrose 
carrier produced an unstable product unless it could be stored in an 
impermeable hermetically sealed enclosure and was produced in a controlled 
low humidity environment. 
The following additional tests were performed as set forth in Table IV, 
each following the same procedure of granulating, drying and spinning as 
described above, using a lime flavored floss sugar in the specified 
quantities, with small quantities of isopropanol, the product being spun 
at medium heat setting. 
TABLE IV 
______________________________________ 
QUANTITIES 
DRUG DRUG SUGAR 
______________________________________ 
acetaminophen 4 gm 50 gm 
phenylpropanolamine 
300 mg 50 gm 
chlorpheniramine maleate 
100 mg 50 gm 
aspirin* 4 gm 50 gm 
______________________________________ 
*Some degradation of the aspirin occurred as evidenced by excessive 
smoking and the characteristic odor of acetic acid. However, the fiber 
product had the characteristic taste of aspirin. 
Various considerations enter into the choice of sugar, or sugars for use as 
the carrier for a given drug. As mentioned previously, the spin 
temperature must not exceed the deterioration temperature for the specific 
drug or active agent. Table V lists the melting points of various sugars, 
all of which can be spun into fibers. 
TABLE V 
______________________________________ 
MELTING POINT 
SUGAR .degree.C. 
.degree.F. 
______________________________________ 
maltose R 103 217.4 
fructose USP 105 221.0 
sorbitol USP 110 230.0 
dextrose USP 146 294.8 
mannitol USP 166 330.8 
sucrose USP 186 366.8 
lactose R 202 395.6 
______________________________________ 
As a result of storage tests it has been discovered that sucrose is 
extremely susceptible to deterioration in the presence of moisture. 
However, it has been discovered that combining as little as 10% lactose 
with the sucrose produces a fibrous product after spinning that is 
significantly more stable. Apparently, the lactose has the physical 
ability of absorbing moisture without crumbling and functions as an active 
antidessicant. The lactose over time merely becomes softer and smoother. 
This becomes evident when pure lactose is spun and observed. Of course, 
pure lactose, with or without a separate sweetening agent, is an excellent 
carrier agent. 
Adding lactose to the composition has another salutary effect. The spun 
fibers of sugar dissolve very rapidly in the mouth although unspun sugar 
dissolves rather slowly. As seen from Table V above, lactose has a much 
higher melting point and, therefore, spin temperature than sucrose. It has 
been discovered that by adding approximately 10% of a flavored lactose 
mixture to the sucrose and drug coprecipitate and spinning the resultant 
mixture at the sucrose temperature, the sucrose drug combination develops 
into fibers while the lactose, having a higher spin temperature, disperses 
uniformly throughout the fibrous mass as lactose granules. When 
administered orally the lactose dissolves more slowly in the mouth, taking 
perhaps one minute, and tends to eliminate any unpleasant aftertaste 
inherent in the drug. An example of a drug that would benefit from this 
treatment is acetaminophen. 
Certain drugs or medicaments cannot be heated above their melting point 
without experiencing excessive deterioration. In such case a sugar should 
be chosen that can be spun effectively at a temperature below the melting 
point of the medicament, and the medicament should be able to disperse 
throughout the fibrous mass similar to the dispersal of the lactose 
throughout the sucrose mass as described above. 
Of the various sugars, maltose and lactose when spun into fibers are much 
more stable than sucrose, that is, they are less affected by humidity. 
Consequently, it is presently preferred to include at least a small 
quantity of either lactose or maltose in any sugar carrier. 
Experience to date has shown that sucrose and lactose can be spun with 
excellent results. Maltose because of its low melting point is ideal for 
certain drugs. However, it has been discovered that when maltose is spun 
using present equipment that is capable of rotating its spinnerette at 
4000 R.P.M., the resultant fibers are much shorter than those obtained 
with sucrose or lactose. It is believed, however, that longer fibers of 
maltose can be obtained by using higher spinnerette speed. 
Attempts to spin methyl cellulose with present equipment at 4000 R.P.M. 
have been met with gumming and charring of the material. It is believed 
that this problem also will be overcome by using higher spinnerette speed. 
Because of the rapid release of a medicament when exposed to moisture, the 
instant product form is ideally suited for use in topical transdermal 
delivery of a medicament. For this purpose, the spun fibrous product can 
be compressed into thin sheets for production of wafers that can be 
combined with adhesive strips to produce bandage strips or patches. When, 
for example, the active agent or ingredient is an antibiotic or a clotting 
factor, it is released upon contact with a wound that emits blood or sera. 
On a burn, appropriate medicament will be released by tissue fluid. The 
invention is also applicable to patch technology in which sweat or skin 
moisture or even ambient moisture causes controlled release of a 
medicament or antigen from a fibrous layer held in contact with or in 
proximity to the skin. 
In another area, certain pediatric suspension drugs, for example, 
amoxicillin, are provided to the pharmacists as a flavored powder in a 
sealed bottle. When the particular drug is to be dispensed, the pharmacist 
adds distilled water and shakes. However, the dissolution of the powder 
takes a long period of shaking wich is counterproductive and irritating to 
the pharmacist. When the present invention is employed and the drug is 
combined with a sugar carrier in fiber form, dissolution in distilled 
water is very rapid and occurs without shaking. 
It is significant that drugs administered through the digestive tract are 
absorbed through the stomach and drain through the portal veins passing 
through the liver before entering into circulation. This reduces the drug 
concentration available in the blood stream and must be compensated by 
high dosage levels. This is avoided by the present invention when the 
fiber form of the medication is placed in the mouth either sublingually or 
buccally because it is absorbed, to a large degree, directly into the 
bloodstream bypassing the liver. This can be a significant advantage with 
drugs such as chlorpheniramine, nitroglycerin and methyltestosterone. 
The present invention has a number of additional advantages. If medication 
in fiber form is placed on the tongue and taken with water, it behaves as 
if you were taking a solution, i.e., a liquid product. It eliminates the 
gagging phenomenon experienced by many individuals with pills or capsules. 
On the other hand if taken on the tongue without water, the dosage form 
manifests the combined characteristics of a buccal and oral dosage form. 
Numerous examples have been mentioned above. However, the fundamental 
concept of transforming a drug or medicament into fiber form, wherein a 
fiber producing material acts somewhat as a scaffold to support the 
medicament for entry into solution almost instantaneously, can be applied 
to an extensive array of materials. In table VI below, the useful 
categories are set forth in the lefthand column in terms of pharmaceutical 
application, while the various forms which the fiber form product can take 
are specified in the righthand column using the following coding scheme: 
A=fiber form for oral administration, including pre-dissolution in a liquid 
vehicle. 
B=fiber form for incorporation in an adhesive bandage or patch. 
C=fiber form for dissolution in H.sub.2 O or other liquid for topical 
application as a solution. 
D=fiber form for bicameral or multicameral vials or pouches to replace 
lyophylized product. 
TABLE VI 
______________________________________ 
CATEGORY FORM 
______________________________________ 
ACNE PREATIONS A,C 
ANALGESICS A,B,C,D 
ANTIPYRETICS A,C,D 
ANTACIDS A 
ANTIFLATULENTS A 
ANTHELMINTICS A,D 
ANTIANGINAL A,D 
ANTIANXIETY A,B,D 
ANTI-ARRYTHYMICS A,D 
ANTIARTHRITICS A,B,C,D 
ANTICOAGULANTS/THROMBOLYTICS 
A,D 
ANTICONVULSANTS/ANTIKINSON 
A,D 
ANTIDEPRESSANTS A,D 
ANTIDIARRHEAL/ELECTROLYTE SOLUTIONS 
A,D 
ANTIFUNGAL A,B,C,D 
ANTITRICHOMONAL A,B,C,D 
ANTIVIRAL AGENTS A,B,C,D 
ANTIGOUT A,B,C,D 
ANTIHISTAMINES A,B,C,D 
ANTIPRURITICS A,B,C,D 
ANTIHYPERTENSIVES A,D 
ANTIINFECTIVES 
(AMINOGLYCOSIDES, SULFONAMIDES, 
CEPHELOSPORINS, PENICILLINS, 
ERYTHROMYCINS, TETRACYCLINES) 
SYSTEMIC OF ABOVE A,D 
LOCAL OF ABOVE A,B,C,D 
ANTIMIGRAINES A,B,D 
ANTINAUSEANTS/ANTIEMETICS A,B,D 
ANTINEOPLASTICS A,D 
ANTIULCER A,D 
ANTIREFLUX A,D 
ANTISPASMODIC A,D 
BRONCHIAL DILATERS/ANTIASTHMATICS 
A,D 
CARDIAC AGENTS A,D 
CONTRACEPTIVES A,D 
HORMONALS A,B,C,D 
STEROIDS A,B,C,D 
COUGH/COLD REMEDIES A,D 
DIURETICS A,D 
HYPOGLYCEMICS A,D 
HYPOLIPIDEMICS A,D 
LAXATIVES A 
TRANQUILIZERS MAJOR & MINOR A,B,D 
MUSCLE RELAXANTS A,D 
OPTHALMIC PREATIONS A,C,D 
POTASSIUM SUPPLEMENTS A,D 
SEDATIVES AND HYPNOTICS A,D 
URINARY ANTINFECTIVES & OTHER 
URINARY AGENTS A,D 
VITAMINS AND MINERALS A,D 
______________________________________ 
The foregoing tabulation is not intended to be exhaustive, but merely 
suggestive and illustrative of the vast area of application of the present 
invention. 
It should be understood that reference herein to topical application of a 
material encompasses both those materials intended to act externally on 
the skin and those having the ability of being absorbed through the skin 
for transdermal systemic activity. 
The term "medicament" and, therefore, "pharmaceutical" as used herein and 
in the appended claims means any drug, pharmaceutical, analytic reagent, 
or other ingredient having therapeutic activity or having utility in 
treating, testing or analyzing physiological conditions or body elements. 
It is intended to encompass ingredients that function as reagents in the 
analysis of substances that are indicative of physiological condition. For 
example, pyridoxal phosphate as used in LDH determination. Pyridoxal 
phosphate was prepared with lactose using IPA as a solvent substantially 
as described above with reference to the compounding of other materials 
with lactose. The composition was spun satisfactorily into a fibrous mass. 
It is advantageous in that it will dissolve in solution much more rapidly 
than existing tablet form of the reagent. 
Having described the present invention with reference to the presently 
preferred embodiments thereof, it will be apparent to those skilled in the 
subject art that various changes and modifications can be incorporated 
without departing from the true spirit of the invention as defined in the 
appended claims.