EP0477289A4

EP0477289A4 - Anhydrous oil-based liquid suspension for delivering a medicament

Info

Publication number: EP0477289A4
Application number: EP19900910225
Authority: EP
Inventors: Akwete L. Adjei; Saul Borodkin; Richard B. Doyle
Original assignee: Abbott Laboratories
Current assignee: Abbott Laboratories
Priority date: 1989-06-13
Filing date: 1990-06-08
Publication date: 1992-07-22
Also published as: KR920702616A; JPH04506216A; CA2060501A1; IE902109A1; WO1991008734A1; EP0477289A1; AU5934290A; GR900100441A; IE902109L; AU639004B2; IL94710A0; IL94710A; PT94372A; GR1001028B

Abstract

Oil-based non-aqueous liquid suspension drug delivery vehicles, suitable for the administration of drugs which are sensitive to water or which have an unpalatable taste comprise an edible oil, a sugar, and a suspending agent. The average particle size of all solid components of the formulation is 30 mu or less which results in formulations which have excellent physical stability including resistance to particle agglomeration, settling and caking.

Description

ANHYDROUS OIL-BASED LIQUID SUSPENSION FOR DELIVERING A MEDICAMENT

Cross-Reference to Related Applications

This application is a continuation-in-part of copending application U.S. Serial No. 365,40 filed June 13, 1989 which is a continuation-in-part of U.S. Serial No.227,559 filed August 4,

1988, now abandoned, which is a continuation-in-part of U.S. Serial No. 096,892 filed

September 14, 1987, now abandoned.

Technical Field This invention relates to liquid drug vehicles. More particularly, this invention concerns liquid oil-based drug vehicles having improved shelf life and stability.

Background of the Invention

Many useful drugs are available only in solid dosage forms (e.g. capsules and tablets), primarily because the drug is unstable in or incompatible with water. Drugs which are unstable in water cannot be formulated as water-based solutions or suspensions and these convenient dosage forms cannot be used, often leading to complaints among juvenile or elderly patients who have difficulty swallowing capsules or tablets. For example, clorazepate dipotassium (sold by Abbott Laboratories under the trade name of TRANXENE®) is one such drug that is not available in liquid form. Clorazepate dipotassium is a minor tranquilizer used for the management of anxiety disorders and for short-term relief of symptoms of anxiety. It is also used as adjunctive therapy in the management of partial seizures and in the symptomatic relief of acute alcohol withdrawal. A description of this drug and its method of manufacture is found in U.S. Patent No. Re.28,315. Vehicles for clorazepate dipotassium are unavailable in liquid form primarily because the drug has significant aqueous stability problems. In the presence of even minute quantities of moisture greater than about 0.3% w/v (i.e.0.3g 100ml) clorazepate dipotassium rapidly hydrolyzes to nordiazepam. This occurs even more rapidly in an acid environment.

In other cases, although a particular drug may be chemically stable in water, liquid formulations such as aqueous solutions and suspensions for oral administration are not used because of the unpalatatability of the particular drug. Unpalatable drugs which are carried in aqueous media are tasted almost immediately upon ingestion and produce an unpleasant taste or after-taste. For example, the antibiotics clarithromycin and erythromycin are valuable therapeutic agents for treating infections and are somewhat unpalatable.

Attempts to solve these problems in the prior art have centered around the formulation of non-aqueous oil-based liquid vehicles for oral administration of such drugs. However, while the formulation of liquid dosage forms of water-sensitive drugs in non-aqueous oil-based vehicles may produce chemically stable suspensions, the suspensions are often not physically stable. That is, such formulations being free of water, do not suffer hydrolysis or other degradation of the active drug component, but are often subject to particle agglomeration, stratification, and caking upon standing and thus have poor shelf life.

There is thus a need in the pharmaceutical formulation arts for a liquid vehicle for drugs which are unstable in water or which produce an unpalatable sensation when administered orally in the form of an aqueous solution or suspension.

United States Patent No.4,080,445 discloses non-aqueous suspensions for oral administration comprising a therapeutically effective amount of a water sensitive drug in an anhydrous vehicle comprising a sugar and a vegetable oil.

Brief Description of the Drawing In the Drawing: FIGURE 1 represents a graph of the particle size distribution of an unmilled prior art drug formulation immediately after formulation and after two weeks of standing at 25°C .

FIGURE 2 represents a graph of the particle size distribution of a milled prior art drug formulation immediately after formulation and after two weeks of standing at 25°c .

FIGURE 3 represents a graph of the particle size distribution of an unmilled prior art drug formulation immediately after formulation and after two weeks of standing at 40°c and 80% relative humidity. FIGURE 4 represents a graph of the particle size distribution of a milled prior art drug formulation immediately after formulation and after two weeks of standing at 40° C and 80% relative humidity.. FIGURE 5 represents a graph of the particle size distribution of a milled drug formulation in accordance with the present invention immediately after formulation and after standing at 25°C for periods of one, two and four weeks . FIGURE 6 represents a graph of the particle size distribution of a milled drug formulation in accordance with the present invention immediately after formulation and after standing at 40°C and 80% relative humidity, for periods of one, two and four weeks . FIGURE 7 represents the stratification rates of prior art milled and unmilled drag formulations and milled and unmilled drug formulations in accordance with the present invention after eight weeks' storage at room temperature. Summary of the Invention

The present invention relates to a pharmaceutical formulation comprising an essentially anhydrous liquid vehicle containing a therapeutically effective amount of a water-sensitive or unpalatable drug. The essentially anhydrous liquid vehicle comprises an oil, a sugar, and a suspending agent. The average particle size of all solid components of the formulation is 30μ or less.

In a preferred embodiment, the formulation also contains a drying agent to help bind any residual water that would otherwise degrade the active therapeutic agent. It is also preferred that buffer be present to stabilize the suspension at a pH favorable to the drug being delivered. In another preferred embodiment the suspension also contains one or more ingredients such as sa and flavor to aid the palatability of the formulation.

The suspension of the present invention provides an environment for water-sensitive or unpalatable drugs which is both chemically and physically stable. Furthermore, there is no oily taste or mouthfeel or bitter after-taste of the suspension made according to the embodiments containing sugar, salt and flavorings.

The foregoing features and advantages of the present invention will be further understood upon consideration of the following description of the preferred embodiments.

Description of the Preferred Embodiments Generally, the suspension of the present invention is an anhydrous oil-based liquid suspension for delivering a medicament As used herein, the term "anhydrous" means having les than about 0.8% w/v moisture. In the preferred embodiments, the suspension contains less than about 0.3% w/v moisture. In addition to oil, the suspension contains a suspending agent which forms a protective colloid around the drug to protect the drug from moisture and assure that the medicament is uniformly dispersed within the suspension.

The oil is preferably one that is considered safe for oral consumption, and is relatively stable. Furthermore, the oil should not be incompatible with the drug being delivered. Preferred oils are selected from mixed triglycerides derived from capric, caproic, and caprylic acids. Furthermore, the vegetable oils containing glycerides of saturated or unsaturated aliphatic acids, such as stearic, palmitic, lauric, margaric, linoleic, linolenic, and myristic acids are suitable for u in the present invention. The most preferred embodiments presently use a winterized safflower o available from California Oils, Richmond, California.

Generally, suspending agents function to suspend the drug uniformly in the oil-based vehicle so that dosages of the drug are uniform. Suitable suspending agents for use in the fomulations of the present invention include bentonite (a finely powdered montmorillonite aluminum silicate which is available under the tradename Bentone® from American Colloid Corporation); finely powdered sodium calcium alginate (available under the trade name Kelset® from Kelco, a division of Merck & Company); trihydroxystearin and hydrogenated castor oil (available under the tradename Thixcin® from NL Chemicals, Highstown, New Jersey); cellulose derivatives; silicates; bentonites; stearates; silicon dioxide; and acacia. In a preferred embodiment of the present invention, the suspending agent is finely powdered sodium calcium alginate. Suspending agents act to slow down stratification and sedimentation of suspended particles by increasing the viscosity of the liquid and thereby improving the bouyancy of the solids suspended in the liquid. It is theorized that the powdered sugar and finely powdered sodium calcium alginate react with the drug to form a protective colloid around the drug particles in the oil-based vehicle resulting in a dispersed system that is highly stabilized. Further, the complex formed by the drug, suspending agent, and sugar provides a complex pathway for moisture to diffuse through. In those cases where the active drug component of the formulation is moisture sentsitive, the drug is shielded by the protective colloid and any moisture that is present in the oil-based vehicle is kept away from the drug. In those cases where the active drug component of the formulation has an unpalatable taste, the protective colloidal shield formed around the drug diminishes the undesirable taste effect while the liquid formulation is in the mouth cavity.

In one preferred embodiment, a drying agent is also included in the suspension. The drying agent is a hygroscopic compound that absorbs or adsorbs water found in the suspension and which may degrade the drug. The drying agent may, in some circumstances, also function as the suspending agent For example, silica gel has been found to have good suspending properties as well as good water absorbing properties. A preferred drying agent in formulations of the present invention is silica gel.

Virtually any sweetener or sugar that is physically and chemically compatible with the drug being delivered is suitable for use in the formulations of this invention.. The preferred sweetener used is sucrose, and is most advantageously micronized and superfine so as to disperse easily in the suspension. Other sugars, however, such as maltose, fructose, sorbitol and xylitol may also be used.

Other preferred embodiments also contain flavor and salt. These ingredients help to make the otherwise unpalatable oil-based suspension palatable, in cases where the oil employed has an unpleasant taste or the active drug component of the formulation is bitter or has an unpalatable taste. A preferred flavoring agent is a mixture of vanilla and peppermint extracts, but may also include other oil compatible flavoring agents, such as cherry, chocolate, cinnamon, coconut, coffee, orange, lemon, lime, strawberry, banana and peanut In preferred embodiments the flavoring agents are free of glycol and alcohol, both of which degrade some drugs such as clorazepate dipotassium. The salt is believed to function primarily as a flavor enhancer to avoid a bland tasting product. The salt also masks the oiliness of the vehicle. It should be present in an amount sufficien to mask the oiliness of the oil based suspension without producing a noticeable salty taste. Sodium chloride is the preferred flavor masking agent Another suitable masking agent is potassium chloride.

In other preferred embodiments, the formulations of the present invention contain an alkaline buffer and a preservative. The alkaline buffer maintains the pH at a level at which the drug is stable. Clorazepate dipotassium, for example, is most stable at a pH greater than about 9.0. In such cases, potassium carbonate is the preferred buffer; however, other carbonates, hydroxides, oxides and organic amines may be used. Suitable preservative agents include the paraben class of compounds. Most preferred is a combination of parabens, such as those marketed under the tradename Aseptoform-M® (methylparaben) and Aseptoform-P® (propylparaben) available from Mallinckrodt, Inc. of St. Louis, Missouri. Any biologically acceptable benzoate or other preservative system that does not complex with or solubilize the drug to be delivered is also suitable.

The presence of surfactants has also been found to be advantageous to the physical stability of the suspension. Most surfactants that are compatible with the drug to be delivered as well as the oil vehicle are deemed suitable for use in the present invention. The preferred surfactant is marketed under the tradename Emulphor EL 719P® by GAF Corp., Wayne, N.J., a polyoxyethylated vegetable oil having low dioxin levels.

Generally, the ingredients of the suspension of the preferred embodiments of the present invention are present in the following amounts: a therapeutically effective amount of a medicament, about 30% w/v to about 75% w/v sugar, about 30% w/v to about 75% w/v oil, about 0.05% w/v to about 5% w/v suspending agent, about 0.05 w/v to about 2% w/v salt, about 0.01% w/v to about 2% w/v alkaline buffer, about 0.01% w/v to about 3% w/v preservative, less than about 5% w/v surfactant, and about 0.01% w/v to about 5% w/v flavor. Formulations having less than about 30% w/v sugar are generally unpalatable, while those having more than about 75% w/v generally have a consistency that is too thick.

More preferably, the ingredients are present in the following ranges: a therapeutically effective amount of a medicament about 40% w/v to about 65% w/v sugar, about 45% w/v to about 65% w/v oil, about 0.1% w/v to about 2% w/v suspending agent about 0.2% w/v to about 1% w/v salt, about 0.05% w/v to about 1% w/v alkaline buffer, about 0.1% w/v to about 1% w/v preservative, less than about 2% w/v surfactant, about 0.01% w/v to about 3% w/v flavoring.

It has been found, in accordance with the present invention, that even with the use of a suspending agent to help maintain the uniformity of the suspension over time, there is still a tendency for the suspensions to stratify, cake, and/or undergo particle agglomeration over time. To counteract this tendency, the formulations in accordance with the present invention are subjected to milling to reduce the average particle size of all solid contained in the mixture to less than about 30μ, preferably to less than 10μ-20μ. The milling step may be performed by any conventional technique known to those skilled in the pharmaceutical formulations arts as, for example, liquid milling. In the illustrative Examples presented below, the preformulations were passed through either a Fryma MZM- Vk7 Delmix mixer or a Manton-Gaulin homogenizer. In most cases a single pass is sufficient to reduce the average particle size of the solids contained in the formulations to a value below the desired level of 30μ, often below about 20μ. If needed, the material can be subjected to two or more passes through the mill to obtain the desired average particle size.

As shown by Examples 16 - 20 below, when this is not done, the rate of stratification, particle agglomeration and caking is accelerated with attendant decrease in the shelf life of the finished formulation.

Example 1 Neobee® oil (320 g) was combined with 5 g of Bentone 34 and 290 g sugar. Sodium chloride powder (1.84 g) was then added. To 100 ml of the above mixture was added 180 mg of clorazepate dipotassium. The ingredients were mixed well. The resulting formulation tasted slightly saline, moderately sweet, with an oily and slightly bitter aftertaste.

Example 2

To 244 g of the mixture of Example 1 was added 4 g surfactant PVP K30 (polyvinyl pyrolidone having an average molecular weight of about 30,000). The resulting mixture was smooth, thin, and free flowing. To this mixture was then added 0.59 g of vanilla flavor. The taste was good, but the mixture turned very thick. An additional 244 g of the mixture of Example 1 was added to thin out the suspension. The resulting mixture was thick but pourable and had excellent taste.

Example 3

Clorazepate dipotassium (375 mg )was mixed with 250 ml of a vehicle produced in accordance with the method of Example 2. The taste of the resulting formulation was excellent, but some bitterness of the drug was noted.

Example 4

Neobee oil M5, (300 g), 300 g powdered sugar 12X and 8.85 g of Bentone 34 were combined. Some evidence of thixotropy was noted at final volume. Vanilla flavor (1.0 g) was added, causing the suspension to thicken significantly. The ingredients were mixed well at high speed for 15 minutes. An additional 70.38 g of Neobee oil M5 was added to 2.0 g sodium chloride which had been reduced to a fine powder in a mortar/pestle before addition to the suspension. In order to formulate a suspension containing 7.5 mg drug per 5ml of suspension, 300mg of clorazepate dipotassium was added to 200 ml of a vehicle produced as above and then mixed well. The resulting mixture was heavy, thixotropic and tasted good.

Example 5 Neobee oil M5 (600 g) and 8.85 g of Bentone 34 were mixed together well. Powdered sodium chloride (3.60 g) was added with good mixing. Powdered sugar 12X (517 g) was added and mixed until smooth. The resulting mixture was allowed to deaerate. An additional 34 g of Neobee M5 oil was then added to bring the volume of the mixture to 1.0 liter, and then mixed until uniform. A small amount of vehicle was removed and mixed with 1.50 g of clorazepate dipotassium until smooth, and then added back into the main batch and mixed well. Vanilla flavor (1.80 g) was added. The mixture became thixotropic after the addition of vanilla. The taste of the suspension was good.

Example 6 To 6.30 kg Neobee M5 oil was mixed 86.0 g of Bentone-34® . Powdered potassium carbonate (10.0 g) and 35.0g of powdered sodium chloride were mixed with above oil mixture to make a smooth paste. The paste was diluted with additional oil and mixed until uniform consistency was attained. The diluted paste was then added to the main batch. Clorazepate dipotassium was mixed with a small amount of oil until smooth, and then diluted further and added to the main batch. 5.20kg powdered sugar 12X was slowly added to the main batch and mixed for approximately 1 hour. Immediately after all the sugar was added the suspension showed thixotropic character. After 1 hour of mixing the mixture became smooth and uniform, and lost its thixotropic character. Flavor (15 ml) was then added. Emulphor El 719P surfactant was added to thicken the mixture. The mixture was passed through a Manton-Gaulin homogenizer at 1500 psi to yield a smooth and uniform product. The product was placed in a vacuum for 1 hour to deaerate. The taste of the suspension was good.

Example 7 From an initial amount of 1833 g Neobee oil, 1 liter Neobee oil was taken and mixed with 39 g Emulphor EL 719P. Bentone 34 (25 g) was blended with Neobee oil and added to the main batch. Powdered sodium chloride (10 g) was blended with a small amount of Neobee oil and then added to the main batch. A preservative agent having 6.8 g Aseptoform M and 3.4 g Aseptoform P was mixed in 40 g of oil and heated until completely in solution, and then added to the main batch. The balance of the oil was then added and blended with a small amount of oil and added to the main batch. Clorazepate dipotassium (4.46 g) was blended with a small amount of oil and added to the main batch. The balance of the oil was added and blended. Powdered sugar (1513.0 g) was mixed in and deaerated. Natural and artificial vanilla/peppermint extract (4.5 ml, obtained from Florasynth, Des Plaines, Illinois) was also mixed in. The entire mixture was passed through a Manton & Gaulin homogenizer to obtain a mixture with an average particle size below about

30 μ. The mixture was smooth, uniform and had good taste.

Example 8 A placebo vehicle was prepared by mixing a small amount of Neobee M5 oil with 85.5 g of Bentone 34. The Bentone 34/Neobee oil mixture was then added to approximately 6.0 kg of Neobee oil. Powdered sugar 12X (6.17kg ) and 36.00 g powdered sodium chloride were mixed in. The resulting mixture was thick after the first hour of mixing with a turbine blade, but thinned out after 3 hours mixing. The taste of the suspension was good.

Example 9 A prototype stability batch was prepared by mixing 2.95 kg safflower oil with 5.0 g Aseptoform-M® and 1.0 g Aseptoform-P®. The mixture was heated to approximately 80°C and 45.0 g and 12.5 g Thixcin-R were added. After dissolving the ingredients, the mixture was cooled to room temperature, and vacuum placed on the vehicle. Clorazepate dipotassium (7.5 g) and 10 g potassium carbonate were then added while the vehicle was being mixed under vacuum. Sodium chloride (17.5 g) and 3.0 kg of powdered sugar were added and homogenized using a Fryma MZM-Vk7 Delmix mixer while still under vacuum. Flavor (7.5 g) was then added and the resulting mixture mixed for approximately 15 minutes. The resulting mixture was milled using a Fryma M5-18 Coball mill (obtained from Fryma, Inc., 40 Ethel Road, Edison, N.J.) to obtain a smooth, uniform formulation having the desired average particle size and acceptable taste and stability requirements.

¹ The preparation and use of 8-chloro-6-phenyl-4H-[l,2,4]triazolo[4,3-a][l,4]benzodiazepine, having the generic name estazolam, is disclosed in United States Patent No. 3,701,782.

Neobee M5 oil (400 ml) was heated to approximately 90°C and then allowed to stand for approx. 1 hour to equilibrate. Aseptoform M and P powders were mixed in until dissolved. Kelset,® Thixcin®, and Tween 80 were mixed to form an uniform dispersion. Estazolam was added and homogenized in a beadmill or a high energy mill. Flavors were then added until the resulting product was uniform. The volume of the resulting product was adjusted to 1 liter with Neobee Oil as required.

The formulations of Examples 11-16 were prepared using the general method detailed in Example 9.

² The preparation of clarithromycin is disclosed in United States Patent No. 4,331,803. Example 13

³ N-2-[benzo[b]thien-2-yl]ethyl-N-hydroxyurea is an inhibitor of the lipoxygenase enzymes and is useful in the treatment of inflammatory and allergic disease states. Its preparation and use is disclosed in United States Patent No. 4,873,159.

Example 14

Ingredient w/v Percent

8-Chloro-6-phenyl-4H-[l,2,4]- triazolo[4,3-a][l,4]benzodiazepine 5.00

Methylparaben 0.20

Propylparaben 0.10

Sodium chloride 0.35

Kelset® 0.90

Powdered sugar, 12X 45.00

Flavor enhancer, Prosweet® 0.25

Safflower oil, q.s. 100.00

Example 15

Ingredient w/v Percent

Valproic acid 5.00 Methylparaben 0.20 Propylparaben 0.10 Sodium chloride 0.35 Kelset® 0.90 Powdered sugar, 12X 45.00 Flavor enhancer, Prosweet® 0.25 Safflower oil, q.s. 100.00

Example 16

Ingredient w/v Percent

α-Methyl-4-(2-methylpropyl)benzeneacetic acid⁴ 5.00 Methylparaben 0.20 Propylparaben 0.10 Sodium chloride 0.35 Kelset® 0.90 Powdered sugar, 12X 45.00 Flavor enhancer, Prosweet® 0.25 Safflower oil, q.s. 100.00

The preparation and use of α-methyl-4-(2-methylpropyl)benzeneacetic acid, having the generic name ibuprofen, is disclosed in United States Patents No.'s 3.228,831 and 3,385,886.

Example 17 An oil-based aspirin suspension was prepared in accordance with the teachings of United States Patent 4,080,445 to Lin, et al. The composition of the formulation was as follows:

Ingredient Weight (g)

Aspirin 6.0

Sucrose, powdered 27.5

Syloid® 1.0

Sesame oil 100.0

The sample was not milled following thorough mixing. The composition was tested for particle size distrinbution just after formulation and two weeks later at two different temperatures (25°C and 40°C ) . The particle size distribution graphs for this formula at 25°C and 40°C and 80% relative humidity appear in Figures 1 and 3, respectively. As can be seen from those graphs, considerable separation was noted after two weeks standing. Particle agglomeration and caking was noted since thorough shaking of the bottle and its contents after two weeks standing did not yield a uniform suspension. Gross separation and caking was noted in the formulation after standing for four weeks.

Example 18

A formulation having the same composition as Example 17 was prepared with the exception that, following thorough mixing of the ingredients, the formulation was subjected to milling to reduce the average particle size to a value below 30μ in accordance with the teachings of this invention. The formulation was subjected to particle size analysis immediately after formulation and again after two weeks standing at 25°C and at 40°C and 80% relative humidity . The results of these particle size analyses appear in Figures 2 and 4, respectively.

As can be seen by the data appearing in those graphs, the formulation had considerably greater physical stability than the similar formulation which had not been subjected to milling.

Example 19 A formulation containing clorazepate dipotassium was made having the same composition as that given in Example 11 above, but omitting the milling step. The formulation was subjected to particle size analysis immediately after formulation and again after two weeks and four weeks standing at 25°C and at 40°Cand 80% relative humidity. The results of these analyses appear in

Figures 5 and 6. As can be seen by those data, the formulations are quite stable with even a slight, but unexplainable decrease in average particle size upon standing. Example 20

The tendency of each of the formulations of Examples 11 (present invention, milled), 17

(prior art formulation, unmilled), 18 (prior art formulation, milled) and 19 (present invention, unmilled) to undergo stratification upon standing was measured by checking the average stratification rate and main separated solid volume at different levels in the formulation after standing. The results of these tests appear in Figure 7 where it can be seen that formulations made in accordance with the present invention have exceptional physical stability.

The foregoing examples are provided to enable one skilled in the art to practice the present invention, but are merely illustrative thereof and are not to be read as limiting the scope of the invention as defined by the appended claims.

Although the present invention has been described in connection with the presently preferred embodiments, those skilled in the art will recognize many modifications to sequence, arrangement, portions, elements, and materials which can be used in the practice of the invention without departing from its scope. It is intended that such changes and modifications can be covered by the following claims.

Claims

1. A non-aqueous liquid suspension drag delivery system for water-unstable or unpalatable drugs having improved physical stability comprising a therapeutically effective amount of a water-unstable or unpalatable drug; an edible oil; a sugar, and a suspending agent; said liquid suspension drag delivery system characterized by an average particle size of all solid components of less than about 30 μ

2. A non-aqueous liquid suspension drug delivery system for water-unstable or unpalatable drugs as defined by Claim 1 characterized by an average particle size of all solid components of less than about 20μ.

3. A non-aqueous liquid suspension drag delivery system in accordance with Claim 1 comprising a therapeutically effective amount of a medicament; between about 30% w/v to about 75% w/v sugar; between about 30% w/v to about 75% w/v oil; between about 0.05% w/v to about 5% w/v suspending agent between about 0.05 w/v to about 2% w/v salt; between about 0.01% w/v to about 2% w/v alkaline buffer, between about 0.01% w/v to about 3% w/v preservative; less than about 5% w/v surfactant; and about 0.01% w/v to about 5% w/v flavor.

4. A non-aqueous liquid suspension drug delivery system in accordance with Claim 2 comprising a therapeutically effective amount of a medicament; between about 40% w/v to about 65% w/v sugar; between about 45% w/v to about 65% w/v oil; between about 0.1% w/v to about 2% w/v suspending agent; between about 0.2% w/v to about 1% w/v salt; between about 0.05% w/v to about 1% w/v alkaline buffer, between about 0.1% w/v to about 1% w/v preservative; less than about 2% w/v surfactant; and between about 0.01% w/v to about 3% w/v flavoring.

5. A non-aqueous liquid suspension drag delivery system in accordance with Claim 1 wherein said medicament is clorazepate dipotassium.

6. A non-aqueous liquid suspension drag delivery system in accordance with Claim 1 wherein said medicament is clarithromycin or a pharmaceutically acceptable salt thereof.

7. A non-aqueous liquid suspension drag delivery system in accordance with Claim 1 wherein said medicament is erythromycin or a pharmaceutically acceptable salt thereof. 8. A non-aqueous liquid suspension drag delivery system in accordance with Claim 1 wherein said medicament is N-2-[benzo[b]thien-2-yl]ethyl-N-hydroxyurea or a pharmaceutically acceptable salt thereof.

9. A non-aqueous liquid suspension drag delivery system in accordance with Claim 1 wherein said medicament is α-methyl-4-(2-methylpropyl)benzeneacetic acid or a pharmaceutically acceptable salt thereof.

10. A non-aqueous liquid suspension drag delivery system in accordance with Claim 1 wherein said medicament is valproic acid or a pharmaceutically acceptable salt thereof.

11. A non-aqueous liquid suspension drag delivery system in accordance with Claim 1 wherein said medicament is 8-chloro-6-phenyl-4H-[l,2,4]triazolo[4,3-a][l,4]benzodiazepine or a pharmaceutically acceptable salt thereof.