Abstract:
A pharmaceutical delivery system for oral administration of a pharmaceutical agent comprises: (a) a squeezable container having an outlet defining a flow channel, (b) a channel closure device adapted to selectively close or open the flow channel; and (c) within the container, at least one dose of a pharmaceutical composition, the composition being a semisolid material that is storage stable, and consists of mutually compatible components, the components comprising (i) an effective amount of an orally active pharmaceutical agent useful for systemic treatment, and (ii) a palatable pharmaceutically acceptable vehicle, comprising a liquid base selected from the group consisting of water, propylene glycol, polyethylene glycol, glycerin, and mixtures thereof, a thickening agent selected from the group consisting of starch, modified starch, sodium carboxymethyl cellulose, microcrystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, other cellulose derivatives, acacia, tragacanth, pectin, gelatin, polyethylene glycol, and water-soluble carboxyvinyl polymers, the pharmaceutical composition having a consistency which allows the composition to be squeezed by manual pressure through the flow channel, whereby in response to pressure on the container when the flow channel is open, a predetermined unit dose of the pharmaceutical composition can be easily squeezed from the container into a receptacle, measured, and administered orally without spilling any of the composition from the container or the receptacle.

Description:
This application is a continuation of application No. 08/114,315, filed Aug. 30, 1993, now U.S. Pat. No. 5,881,926, which is a continuation-in-part of copending application Ser. No. 08/029,443, filed Mar. 11, 1993 now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     This invention is concerned with new formulations of orally active pharmaceutical agents and a device for administration thereof. More particularly this invention is concerned with formulations in semisolid form for oral administration of pharmaceutical agents used for systemic treatment, preferably contained in a single dose packet or in a multi-dose measuring device which can be used to measure as well as to administer the formulation, and to a childproof closure useful for the device. 
     Heretofore, pharmaceutical agents for systemic treatment by oral administration have generally been formulated in solid form as pills or capsules or in liquid form. Children, the elderly and people with motor problems often have problems swallowing pills and capsules. It is also difficult to administer medicine in liquid form to children, even when the liquid has been thickened to a syrup, and the elderly and those with motor problems also have difficulty with the self administration of liquid, especially when it is necessary to measure a specific unit dose. 
     Important requirements for a non-solid pharmaceutical formulation for oral administration include palatability to children and adults, stability, i.e. a long shelf life, compatibility of formulation components with active agent and desirably, ease of administration of the required dose. 
     Pharmaceutical preparations in semisolid form for topical application are well known in the art. Such preparations include gels, pastes, creams and ointments for use on the skin, teeth and mucous membranes. Antacids and anti-ulcer agents in suspension and gel form for coating the mucous lining of the stomach are also well known in the art. 
     In a few instances, systemically useful pharmaceutical agents have been incorporated into gelled vehicles, as for example those disclosed in U.S. Pat. Nos. 4,305,933, 4,576,645 and 4,883,660. However, these vehicles all suffer from one or more disadvantages, such as the presence of a component which is undesirable for administration to children and/or is incompatible with many pharmaceutical agents, the presence of an emulsion which is difficult to manufacture and tends to be unstable and/or inadequate viscosity. 
     There is a need for an economical formulation of systemic pharmaceutical agents in easily-administered form, as well as a need for easily administered non-spill pharmaceutical formulations which can be measured and administered effortlessly to children and by adults with motor problems. There is also a need for a simple to use and easily manufactured device for the measurement and administration of a predetermined dose of a pharmaceutical agent and also for a device of this type which is substantially tamper-proof in so far as young children or individuals with limited mental capacity are concerned. 
     While devices for dispensing a measured amount of a composition have been disclosed, for example in U.S. Pat. Nos. 3,104,032 and 3,383,081, these devices tend to be complicated and are not completely satisfactory for easy delivery and administration of a measured amount of a pharmaceutical composition. 
     SUMMARY OF THE INVENTION 
     An object of the invention is the provision of pharmaceutical agents useful for systemic treatment by the oral route in a form which is convenient to administer to children and which is convenient for self administration of aging adults, as well as adults with motor problems. 
     Another object of the invention is the provision of pharmaceutical agents useful for systemic treatment by oral administration in a composition which is provided in a device from which it is particularly easy to administer and convenient to measure single dosage units of the composition. 
     A further object of the invention is the provision of pharmaceutical agents useful for systemic treatment by oral administration in a form which avoids the problems of liquid formulations, such as spillage. 
     Another important object of the invention is the provision of a device for easily administering pharmaceutical formulations in semisolid form in dosage units. 
     Still another important object of the invention is the provision of a device for easily administering pharmaceutical formulations in semisolid form in dosage units which is substantially tamper proof by young children or individuals with limited mental capacity. 
     A further important object of the invention is the provision of a childproof closure useful for a device for holding pharmaceutical formulations. 
     These and other objects of the invention are achieved by the invention set forth below. 
     It has been discovered that pharmaceutical agents in semisolid form, such as a gel or paste, are much easier to administer to children than liquid and solid dosage forms and are much easier for an aging adult or a adult with motor problems to measure than a liquid and in some cases are easier to swallow than a pill or capsule. It has also been discovered that such compositions can be desirably packaged in a single dosage form or in a multi-dose device which contains measuring and administration means. 
     According to the invention, a pharmaceutical agent useful for oral administration to treat an illness systemically is provided as a semisolid in gel or suspension form, such as a paste, in a composition containing the pharmaceutical agent and a pharmaceutically acceptable vehicle comprising a thickening agent and a liquid base compatible with the pharmaceutical agent and thickening agent in which the pharmaceutical agent is soluble. 
     In a preferred embodiment of the invention, a single dose of the semisolid pharmaceutical composition is contained in a flexible packet which can be opened by tearing or cutting. 
     In another preferred embodiment of the invention, a device for containing the semisolid pharmaceutical composition is provided which comprises a squeezable container with means for measuring and administering therefrom a single dose of the semisolid composition of the invention and resealing the container thereafter. 
     In a particularly preferred embodiment of the invention, a device for containing multiple doses and measuring a single dose of the semisolid composition of the invention comprises a squeezable container for holding the pharmaceutical composition having an open neck with exterior threads for attaching a cap thereto and a cap with interior threads suitable to engage the outer threads of the neck of the squeezable container, a spoon having a shaft with channel means fixed in the cap so that the bowl-shaped end of the spoon projects outside the cap and the shaft projects into the cap and the channel means are in alignment with the open neck of the squeezable container and sealing means in said cap positioned to seal the container when the cap is fully closed and to provide space for the contents of the container to flow through the channel means into the spoon in response to pressure on the container when the cap is partially opened, whereby contents of the squeezable container can be squeezed into the bowl-shaped end of the spoon and administered therefrom. 
     The device of the invention can be resealed after use by including any of a variety of resealing means in the cap, such as pin inside the cap which rests against and closes the neck of the squeezable container when the cap is tightened after use; a rotatable or pivotable valve and a spring activated step valve, which allow passage of the semisolid composition from the tube to the spoon when open and seal off the contents of the squeezable container when in the closed position. 
     Another embodiment of the invention is a closure which cannot be normally opened normally by a child, which is referred to herein as a childproof closure, and which can be used in the device of the invention. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 illustrates a closed tube containing a semisolid composition of the invention; 
     FIG. 2 illustrates a replacement cap of the invention for the tube of FIG. 1 equipped with a spoon for measuring and administering a dose of the semisolid composition of the invention; 
     FIG. 3 illustrates a tube containing the semisolid composition of the invention with attached replacement cap equipped with a spoon and 
     FIG. 4 shows a section of FIG. 3 along lines 4--4. 
     FIG. 5 illustrates an alternate device of the invention having a resealable cap equipped with a spoon. 
     FIG. 6, which illustrates the cap in closed position and 
     FIG. 7, which illustrates the cap in open position with semisolid composition of the invention being squeezed into the spoon, show sections of the cap of FIG. 5 taken along the line 7--7. 
     FIG. 8 is a perspective view of a cap, partially broken away to reveal the inner structure of the resealing mechanism of another embodiment of the device of the invention; 
     FIG. 9 shows a section of the cap of FIG. 8 taken along the line 9--9. 
     FIG. 10 is a perspective view of a cap, partially broken away to reveal the inner structure of the pivoting valve resealing mechanism of another embodiment of the device of the invention; 
     FIG. 11 is a partial side view of the pivoting valve with a phantom outline of the pivoting valve in the upright closed position shown by the dash-dot line and the open position by the dashed line. 
     FIG. 12 is a perspective view of a cap, partially broken away to reveal the inner structure of a cap with a spring-activated mechanism of another embodiment of the device of the invention; 
     FIG. 13 shows a section of FIG. 13 along the line 13-13. 
     FIG. 14 is another perspective view of a cap, partially broken away to reveal the inner structure of resealing means with a spring-activated mechanism of another embodiment of the device of the invention, which is further provided with means to prevent access of the contents of the tube to children and to prevent tampering; 
     FIG. 15 shows a section of FIG. 14 taken along line 15--15 which illustrates means to prevent access of the contents of the tube to children and 
     FIG. 16 also shows a section of Figure taken along line 15--15 which illustrates means to prevent tampering of the device prior to intended use. 
    
    
     DESCRIPTION OF THE INVENTION 
     The pharmaceutical compositions of the invention are comprised of a pharmaceutical agent in an effective amount for systemic treatment by oral administration in admixture with a pharmaceutically acceptable vehicle comprising a thickening agent in a amount which provides a semisolid, such as a gel or a paste suspension. The semisolid has a Brookfield viscosity at of above 2500 cps, preferably 2500 to 70,000 cps more preferably 3500-65,000 cps and most preferably about 7,500-40,000 cps. In the present application, viscosity refers of Brookfield viscosity, measured at 25° C. and a spindle speed of 10 rpm, unless otherwise noted. 
     The semisolid form is generally a gel or a paste suspension which has the required viscosity to be squeezed easily through a small orifice similarly to tooth paste, dermatological creams, ointments and the like. The particular viscosity above 2500 cps is not critical as long as it fulfills the requirement of being a semisolid which is squeezable through a relatively small orifice such as that usual at the mouth of a flexible tube. 
     In general, the viscosity of the compositions of the invention can be varied by the choice and amount of thickening agent used from about 2500 cps to any greater viscosity which still permits the composition to be readily squeezed through a relatively narrow orifice, i.e. of the order of about 1 to 5 mm in diameter, such as that provided by the opening of a single dose packet or a seal-a-spoon device of the invention. 
     By systemic treatment is meant treatment which affects the body as a whole, as compared to topical treatment, which affects only that part of the body to which it is applied, i.e. skin, teeth or particular mucous membrane, such as the lining of the stomach. 
     Orally active pharmaceutical agents which may be present in the semisolid compositions of the invention are those useful for systemic treatment by oral administration and include for example: 
     analgesics, such as acetaminophen, codeine, aspirin and dihydrocodeinone; 
     anti-inflammatory agents, such as ibuprofen, naproxen and diclofenac; 
     anti-histamines including H 1  -blockers, such as chlorpheniramine, terfenadine, loratidine, astemizole and cetirizine and H 2  -blockers, such as cimetidine and ranitidine; 
     anti-infectives including: antibacterials such as sulfa drugs, i.e. sulfisoxazole; quinolones, i.e. ciprofloxacin and ofloxacin; tetracyclines, i.e. tetracycline; anti-virals, i.e acyclovir and amantadine and anti-fungals, i.e. fluconozole; 
     bronchodilators, such as albuterol, metaproterenol and theophylline; 
     cough suppressants, such as dextromethorphan; 
     expectorants, such as guaifenesin; 
     CNS active agents, including: hypnotics, such as triazolam; sedatives, such as phenobarbital; tranquilizers, such as chlorpromazine and diazepam; antidepressants, such as fluoxetine and nortriptylline; anti-convulsants, such as carbamazepine and ethosuximide and anti-Parkinson&#39;s agents, such as L-DOPA; 
     cardiovascular drugs including: diuretics, such as hydrochlorthiazide; anti-hypertensives including: beta-blockers, such as propranolol; ACE inhibitors, such as captopril and enalapril; calcium channel blockers, such as diltiazem; anti-anginals, same as anti-hypertensive agents; cardiac glycosides, such as digoxin; 
     antineoplastics, such as 5-fluorouracil and cyclophosphamide; 
     cholesterol-lowering agents such as lovastatin; 
     anti-emetics, such as metoclopramide; 
     vitamins, such as A, B 1 , B 6 , C, D 3  and E; 
     minerals, such as iron, calcium and zinc salts and fecal softeners, such as docusate. 
     Useful pharmaceutical agents of course include pharmaceutically acceptable salts and esters of the named compositions. 
     The semisolid compositions of the invention have a liquid base, which is a palatable pharmaceutically acceptable solvent, preferably a solvent which dissolves the active pharmaceutical agent. Preferred solvents include water, propylene glycol, glycerin and mixtures thereof. In some instances it may be necessary to include a compound which is effective to solubilize the active pharmaceutical agent in the solvent, for example, lactic acid is used in an aqueous formulation of ciprofloxacin hydrochloride to solubilize this active ingredient. 
     According to the invention, any pharmaceutically acceptable thickening agent can be used in the compositions of the invention, providing of course that the thickening agent is compatible with the active agent and the solvent base. Examples of useful thickening agents include natural occurring thickening agents or thickening agents derived from naturally occurring materials, such as starch and starch derivatives, for example modified starch; cellulose derivatives, for example sodium carboxymethylcellulose, microcrystalline cellulose and hydroxypropyl cellulose; acacia; tragacanth, pectin and gelatin, as well as totally synthetic thickening agents, such as polyethylene glycol and water soluble carboxyvinyl polymers, such as those sold under the names of carbomer and Carbopol™, which is produced by B. F. Goodrich Chemical Group. Gelatin, cellulose derivatives, polyethylene glycols and water soluble carboxyvinyl polymers are preferred. 
     A sweetener is added to the composition of the invention in an amount necessary to make the semisolid palatable. 
     Ingredients such as flavoring, coloring matter, filler, preservative, buffer, sodium chloride and carriers usual in pharmaceutical compositions can also be present in the semisolid compositions of the invention. 
     In one preferred embodiment, a single dose of the semisolid pharmaceutical composition of the invention is contained in a small flexible packet or sachet which is readily torn or cut so that the contents thereof can be squeezed directly into the mouth, or if preferred, into another vehicle for oral administration. Such a containers are commonly used, for example, for single servings of condiments and can be made of flexible plastic and/or of non-corrosive metal film. 
     In another preferred embodiment, multiple doses of the semisolid pharmaceutical composition of the invention are contained in a device of the invention referred to as a seal-a-spoon which is described in detail below and in the accompanying drawings. 
     With reference to FIGS. 1-4, the tube 1 containing a semisolid pharmaceutical composition of the invention is provided with the cap 3, which can be replaced by the cap 5 shown in FIG. 2. The device with attached cap 5 is illustrated in FIGS. 3 and 4. As is usual, the outside of neck 2 of tube 1 and the inside of cap 5 are provided with corresponding threads, so that the cap can be fixed to the neck of the tube. A spoon shaped projection 7, which is preferably sized to contain a single unit dose of the semisolid composition of the invention contained in tube 1, is connected to the cap 5 by means of the shaft 9, which is provided with a channel 11 adapted to be aligned with the opening of the neck 2 of tube 1, so that the semisolid composition in tube 1 can be squeezed directly from the tube 1 through the channel 11 into the spoon shaped projection 7 and administered therefrom. 
     Seal-a-spoon devices of the invention wherein the cap containing the spoon-shaped projection is provided with resealable means are illustrated in FIGS. 5-15. A seal-a-spoon device of the invention with a &#34;child-proof&#34; mechanism and also with tamper-proof means is illustrated in FIGS. 14-16. 
     As illustrated in FIGS. 5-7, the spoon shaped projection 7 set in cap 5a by shaft 9 is provided with a pin 13 which projects into the inside of the cap 5a and is adapted to rest against the neck 2 of tube 1 and seal the tube when the cap 5a is in the fully closed position illustrated in FIG. 6. When the cap is rotated a few notches, as illustrated in FIG. 7, but not separated from tube 1, the pin no longer rests against the neck of tube 1, which is then unsealed and the semisolid composition in tube 1 can be readily forced through the channel 15, which is present between the shaft 9 and the pin 13, into the projecting spoon 7 and administered directly therefrom. 
     Another embodiment of the seal-a-spoon device of the invention is illustrated in FIGS. 8 and 9 wherein the cap 5c is provided with the rotating valve or stopcock 17 having a channel 19 which can be aligned as shown with the channel 11 in the shaft 9 (not shown) or turned to prevent the flow of semisolid composition from the tube 1, as indicated by the dashed line in FIG. 9. 
     Still another embodiment of the seal-a-spoon device of the invention is illustrated in FIGS. 10 and 11, wherein the cap 5d is provided with the pivoting valve 21 connected to the pivoting hinge 23. The pivoting valve 21 has a channel 25 which is in alignment with the channel 11 of the shaft 9 (not shown) when in the down position illustrated, allowing the flow of semisolid composition from the tube 1 (not shown) into the spoon 7; when the pivoting valve 21 is moved to the upright position, as shown by the dash-dot line of FIG. 11, with the aid of the protuberance 27, the contents of the tube 1 are resealed. 
     Further embodiments of the seal-a-spoon device of the invention are illustrated in FIGS. 12-15. As shown in FIGS. 12 and 13, the cap 5e is provided with a spring biased step cylinder 29 having a channel 31; the spring 33 is held in place by a retaining member 35, such as a screw plug. When the step cylinder 29 is in the normal upright position, the contents of tube 1 (not shown) are sealed; when the step cylinder 29 is pressed to compress the spring 33, so that the channel 31 is in alignment with the channel 11 of the shaft 9 (not shown), the contents of the tube 1 (not shown) can be squeezed into the spoon 7. 
     A childproof and tamper proof seal-a-spoon device of the invention is illustrated in FIGS. 14-16, wherein the cap 5f is provided with a rotating spring biased step cylinder 37 having a channel 39 and also having on its side, near the top, the button 41. The cap 5f is also provided on its outside near the step cylinder 37, with a cavity 43 corresponding in size and shape to the button 41. When the step cylinder 37 is in the normal upright position, the contents of the tube 1 (not shown) are sealed. The step cylinder 37 cannot be depressed unless the button 41 is lined up with the cavity 43 in the cap 5f. In addition, the cavity in the cap 5f is initially sealed with a sheet of plastic 45. When the button is aligned with the cavity of corresponding shape in the cap 5f and pushed for the first time, the plastic sheet 45 is broken. An unbroken sheet 45 means that the cap 5f has not been previously used or tampered with. The cap 5f is a permanent cap which can not be removed by normal means or which has special safeguards against removal. 
     Since the rotating spring biased cylinder 37 cannot be depressed unless the button 41 is first lined up with the cavity 43 in the cap 5f, three different motions are required before the contents of the tube 1 (not shown) can be caused to flow into the spoon 7: aligning the button 41 with the cavity 43 by rotating the step cylinder 37, depressing the step cylinder 37 to align the channel 39 with channel 11 and pressing on the tube 1 to effect the flow of semisolid composition from the tube to the spoon 7. Therefore, this embodiment of the seal-a-spoon device of the invention is considered to be child proof, as well as tamper proof. 
     The childproof closure illustrated in FIG. 14, with or without (not illustrated) the projecting spoon, can be applied to other containers of medicine. 
     The following examples further illustrate the invention, but must not be construed as limiting the invention in any manner. 
     EXAMPLE 1 
     Acetaminophen Formulation Thickened with Polyethylene Glycols 
     Acetaminophen was dissolved in a minimum quantity of water and combined with propylene glycol, a mixture of polyethylene glycols (PEG 400, which has an average molecular weight of Boo and PEG 3350, which has an average molecular weight of 1600), preservative, sweetener and flavoring to provide the following composition in percent by weight. 
     
         ______________________________________PEG mixture     72  Acetaminophen 2.5  Propylene glycol 25  Methylparabens 0.22  Sodium Saccharin 0.2  Cherry essence 0.05  Red DC 33 0.005  Water to 100______________________________________ 
    
     PEG mixtures were varied in the foregoing formula to provide compositions with different viscosities as shown in Table 1. The viscosities were measured by means of a Brookfield Viscometer at 20° C. at a spindle speed of 20 to 100 rpm, depending on medium viscosity, or at 25° C. at a spindle speed of 10 rpm. All of these compositions are useful as semisolids for oral administration and can be packed in single dose containers or-in a multiple dose device of the invention. 
     
                       TABLE 1______________________________________PEG 400       PEG 3350 VISCOSITY  % by wt. % by wt CPS______________________________________60            40       62,640  70 30 39,280  80 20 25,040______________________________________ 
    
     EXAMPLE 2 
     Pseudoephedrine HCl Formulation Thickened with Polyethylene Glycols 
     Pseudoephedrine HCl (0.6%) is incorporated into a formulation base consisting of propylene glycol (25%), polyethylene glycols (73.5%) consisting of 75% PEG 400 and 25% PEG 3350, methyl parabens (0.22%) as a preservative, sodium saccharin (0.2%) as a sweetener, coloring and flavoring matter and water to make 100%. 
     This formulation provides a semisolid of desirable consistency and viscosity which can be packed in a single dose container or a seal-a-spoon device of the invention. 
     EXAMPLE 3 
     Acetaminophen Formulation Thickened with Carboxymethylcellulose 
     Acetaminophen (3.2%) is dissolved in a minimum quantity of water; glycerin (4%) and propylene glycol (25%) are added, after which, sodium saccharin (0.2%), methyl parabens (0.22%) and sodium carboxymethylcellulose (2.4%) are incorporated. Water is then added-to make up 100%. 
     This formulation has a viscosity of 15,000 cps when measured in the same manner as the formulations of Example 1 and has a desirable semisolid consistency useful in packaging in single dose packets or in a multiple dose device of the invention. 
     EXAMPLE 4 
     Dextromethorphan Hydrobromide Formulation Thickened with Carbopol™ 
     Dextromethorphan HBr (0.3%) is dissolved in a mixture of propylene glycol (25%), glycerin (4%) and Carbopol 934P (1%) as a thickening agent. Sweetener, preservative, flavor and color as in Example 1 are optionally added and the mixture is made up to 100% with water. This formulation exhibited a viscosity of 15,000 cps, when measured at 20°-21° C. as in Example 1 and had a desirable semisolid consistency suitable for packaging into single dose packets or in a seal-a-spoon device of the invention. 
     EXAMPLE 5 
     Dextromethorphan Hydrobromide Formulation Thickened with Gelatin 
     A pharmaceutical base is prepared by heating gelatin (2.5%) in water. Glycerin (4%), propylene glycol (25%) and dextromethorphan HBr (0.3%) are mixed into the gelatin solution. Sodium saccharin, methyl parabens, flavor and coloring matter are added as in Example 1 and the formulation is made up to 100% with water. This formulation exhibited a viscosity of 7500 which is suitable for packaging into single packets or a seal-a-spoon device of the invention. The viscosity of this formulation can be increased or decreased within the range of 6000-9000 cps by the addition of more or less gelatin. 
     EXAMPLE 6 
     Caridopa/Levidopa Formulation Thickened with Polyethylene Glycols 
     This is a non-aqueous formulation of caridopa/levidopa, which is useful as an anti-Parkinson medicament containing the following ingredients. 
     
         ______________________________________         weight %/volume______________________________________Carbidopa       0.100  Levidopa 1.000  PEG 400 56.524  PEG 3350 29.120  Propylene glycol 13.000  Saccharine Sodium 0.250  FDC Red #40 0.006______________________________________ 
    
     The formulation, which is prepared by combining the polyethylene glycols with propylene glycol, sweetener and coloring matter and then adding the active agents thereto, has a consistency suitable for use in a single dose packet or in a multiple dose device of the invention. 
     EXAMPLE 7 
     Ibuprofen Formulation Thickened with Sodium Carboxymethylcellulose 
     This semisolid suspension, which contains a non-steroidal anti-inflammatory agent, has the following ingredients and is prepared as indicated in Example 6 by combining the components of the semisolid vehicle and then adding the active constituent thereto. 
     
         ______________________________________            Weight %/Volume______________________________________Ibuprofen          2.000  Citric Acid 0.200  ETDA (Disodium) 0.020  FDC red #40 0.006  Cherry flavor 0.150  Vanilla flavor 0.050  Glycerin 20.000  Sodium carboxymethylcellulose 2.400  Sodium benzoate 0.100  Hydrogenated glucose 6.5  Purified water to 100 cc______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention. 
     EXAMPLE 8 
     Terfenadine Formulation Thickened with Sodium Carboxymethylcellulose 
     A semisolid suspension of terfenadine, which is useful for the systemic treatment of allergies, is prepared as in Example 7 with the following ingredients. 
     
         ______________________________________            Weight %/Volume______________________________________Terfenadine        0.600  Sodium carboxymethylcellulose 2.400  Saccharin sodium 0.250  Hydrogenated glucose 65.000  Imitation raspberry flavor 0.150  Methyl paraben 0.200  Propyl paraben 0.050  FDC yellow #10 0.006  Purified water to 100 cc______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention. 
     EXAMPLE 9 
     Ranitidine Formulation Thickened with Sodium Carboxymethylcellulose and Hydroxypropyl Methylcellulose 
     A semisolid formulation of ranitidine, which is an antagonist to histamine H 2  receptors, is prepared as in Example 7 with the following ingredients. 
     
         ______________________________________            Weight %/Volume______________________________________Ranitidine HCl     1.680  (1.5% Ranitidine)  Dibasic sodium phosphate 0.030  Sodium carboxymethylcellulose 2.400  Hydroxypropyl methylcellulose 0.900  Peppermint flavor 0.100  FDC yellow #10 0.006  Monobasic potassium phosphate 0.020  Butyl paraben 0.180  Propyl paraben 0.500  Sodium chloride 0.050  Sorbitol 70% 30.000  Purified water to 100 cc______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention. 
     EXAMPLE 10 
     Ciprofloxacin HCl Formulation Thickened with Sodium Carboxymethylcellulose 
     A semisolid formulation of ciprofloxacin HCl, which is an antimicrobic agent, is prepared according to Example 7 with the following ingredients. In this formulation lactic acid is used to solubilize Ciprofloxacin HCl and the pH is adjusted to between 3.5-4.6 with HCl. 
     
         ______________________________________            Weight %/Volume______________________________________Ciprofloxacin HCl  10.000  (200 mg Ciprofloxacin)  Saccharin sodium 0.250  Lactic acid 0.020  Sodium carboxymethylcellulose 2.400  Blackberry flavor 0.150  FDC red #40 0.006  FDC red #5 0.002  Dextrose solution 100 cc  (5%) in purified  water to______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention 
     EXAMPLE 11 
     Triazolam Formulation Thickened with Sodium Carboxymethylcellulose 
     A semisolid formulation of triazolam, a hypnotic useful against insomnia, is prepared according to Example 7 with the following ingredients. 
     
         ______________________________________            Weight %/Volume______________________________________Triazolam          0.005  Sodium Benzoate 0.250  FDC yellow #6 0.008  Imitation orange flavor 0.120  Sodium Saccharin 0.220  Sodium carboxymethylcellulose 2.800  Hydrogenated glucose 20.000  Purified water to 100 cc______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention. 
     EXAMPLE 12 
     Fluconazole Formulation Thickened with Sodium Carboxymethylcellulose 
     A semisolid formulation of fluconazole, a broad spectrum antifungal agent, was prepared as in Example 7 with the following ingredients. 
     
         ______________________________________            Weight %/Volume______________________________________Fluconazole        2.000  Sodium carboxymethylcellulose 2.400  FDC red #40 0.006  Cherry flavor 0.150  Sodium saccharin 0.240  Sodium chloride 0.050  Purified water to 100 cc______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention. The formulation should be stored at a temperature below 25° C., but not lower than 5° C. and must be supplied in a container made of polyvinyl chloride, Baxter Viaflex. 
     EXAMPLE 13 
     Acyclovir Formulation Thickened with Sodium Carboxymethylcellulose and Microcrystalline Cellulose 
     A semisolid formulation of acyclovir, an anti-viral agent, is prepared according to Example 7, with the following ingredients. 
     
         ______________________________________            Weight %/Volume______________________________________Acyclovir          4.000  Methyl paraben 0.100  Propyl paraben 0.020  Sodium carboxymethylcellulose 2.400  Peppermint flavor 0.150  Glycerin 20.000  Microcrystalline cellulose 0.900  Sorbitol 70% 20.000  Sodium saccharin 0.30  FDC yellow #6 0.008  Purified water to 100 cc______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention. 
     EXAMPLE 14 
     Fluoxetine HCl Formulation Thickened with Sodium Carboxymethylcellulose 
     A semisolid formulation of fluoxetine hydrochloride, and anti-depressant drug, is prepared according to Example 7 with the following ingredients. 
     
         ______________________________________            Weight %/Volume______________________________________Fluoxetine HCl     0.400  Benzoic acid 0.200  Imitation cherry flavor 0.150  FDC red #40 0.006  Glycerin 30.000  Sodium saccharin 0.200  Methyl paraben 0.160  Hydrogenated glucose 65.000  Sodium carboxymethylcellulose 2.500  Purified water to 100 cc______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention. 
     EXAMPLE 15 
     Propranolol HCl Formulation Thickened with Sodium Carboxymethylcellulose and Microcrystalline Cellulose 
     A semisolid formulation of propranolol hydrochloride, which is a synthetic beta adrenergic receptor blocker, is prepared according to Example 7 with the following ingredients. 
     
         ______________________________________          Weight %/Volume            20 mg/5 cc  40 mg/5 cc______________________________________propranolol HCl  0.400       0.800  Cherry flavor 0.150  Peppermint flavor  0.100  FDC red #40 0.006  FDC yellow #6  0.008  Microcrystalline cellulose 0.900 0.900  Sodium carboxymethylcellulose 2.400 2.400  Methyl paraben 0.200 0.200  Propyl paraben 0.050 0.050  Sodium saccharin 0.250 0.250  Purified water to 100 cc 100 cc______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention. 
     EXAMPLE 16 
     Enalapril Maleate Formulation Thickened with Sodium Carboxymethylcellulose 
     A semisolid formulation of enalapril maleate, which is useful for treatment of hypertension and heart failure, is prepared according to Example 7 with the following ingredients. 
     
         ______________________________________            Weight %/Volume______________________________________Enalapril maleate  0.100  FDC red #40 0.007  Saccharin sodium 0.250  Imitation cherry flavor 0.150  Sodium carboxymethylcellulose 2.800  Methyl paraben 0.220  Purified water to 200 cc______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention. 
     EXAMPLE 17 
     Diltiazem HCl Formulation Thickened with Sodium Carboxymethylcellulose, Hydroxypropyl Cellulose and Polyethylene Glycol 
     A semisolid formulation of diltiazem hydrochloride, which is a calcium antagonist, is prepared according to Example 7 with the following ingredients. 
     
         ______________________________________            Weight %/Volume______________________________________Diltiazem HCl      0.600  FDC yellow #6 0.006  Peppermint flavor 0.100  Hydroxypropyl cellulose 0.900  Sodium carboxymethylcellulose 2.400  Hydrogenated glucose 60.000  Saccharin sodium 0.220  Polyethylene glycol 1500 10.000  Purified water to 100 cc______________________________________ 
    
     The consistency of this formulation is suitable for use in a single dose packet or in a multiple dose device of the invention. 
     EXAMPLE 18 
     Lovastatin Formulation Thickened with Sodium Carboxymethylcellulose and Polyethylene glycol 
     A semisolid formulation of lovastatin, a cholesterol lowering agent, is prepared according to Example 7 with the following ingredients. 
     
         ______________________________________            Weight %/Volume______________________________________Lovastatin         0.200  Butylhydroxy toluene 0.200  Sodium carboxymethylcellulose 2.500  FDC red #40 0.006  Peppermint flavor 0.100  Sodium saccharin 0.250  Polyethylene glycol 1500 25.000  Methyl paraben 0.200  Purified water to 100 cc______________________________________