JP2528946B2 - Composition for drug delivery - Google Patents

Description

FIELD OF THE INVENTION The present invention relates to drug delivery compositions, and in particular to the delivery of comfortable, non-flavored drugs or drugs in which solid state intake is undesirable.

Background of the Invention It is well known to use flavors to mask the flavor of drugs. However, flavor components are not sufficient to mask certain drugs and vitamins. As such, physical methods have been developed to provide encapsulation and chemical barriers, masking their undesirable flavor properties.

Certain methods used for vitamins are described in US Pat.
911, 3080292, 3080293 and 3379994. These methods produce a product in the form of a beadlet. While effective at masking flavors, these beadlets can cause additional problems for certain drugs and certain types of patients.
For example, patients who have problems when taken in solid dosage forms
The drug produced by this beadlet method cannot be used.

Also, products such as potassium chloride cannot be effectively ingested in the beadlet form described in the prior art.
Solid potassium chloride is known to deposit along the inner walls of the stomach and intestines, causing ulcers in the gastrointestinal wall. This ulcer or bleeding on the stomach is a highly undesirable side effect, especially for younger patients. That is, the treatment of one disease causes another serious medical problem.

The present invention is advantageous in that the flavor mask particles can be administered in liquid form. The present invention is also advantageous in that it can produce products that exhibit economically and commercially desirable properties. Furthermore, the compositions of the present invention are advantageous in that they do not affect the active properties of the administered drug. Another advantage is that
Particularly, it can be administered in a solid drug form to a patient who cannot take a large amount of the drug. Finally, the compositions of the present invention solve the long-felt need in the art.

(Summary of the Invention) The composition for drug delivery of the present invention can mask the taste of an active agent (also referred to as an active agent) and prevent gastric ulcer. The composition comprises a solid active agent that has been rendered taste-masked and hydrophilic such as bitterness, the density of the taste-masked active agent having a density approximately equal to the density of the liquid carrier in which the active agent is suspended. However, its action can be explained as follows.

The drug delivery composition of the present invention is a heterogeneous system, which is subject to gravity. That is, since the individual solid particles constituting the composition have densities slightly different from each other, when dispersed in a liquid, they move at different velocities according to the densities, and have a density smaller than that of the liquid carrier. Solid particles gradually rise in the carrier to reach the top of the liquid surface, while solid particles having a large density descend and move to the bottom. This phenomenon can be shown by Stokes' law below.

To administer the masked activator particles of the invention,
Usually, the particles are added to a liquid, stirred, and then drunk. Therefore, by equalizing the densities of the masked active agent particles and the liquid carrier, the masked active agent particles can maintain a uniform and stable suspension state for a relatively long period of time. As a result, the particles are
For a predetermined period of time (for example, about 60 seconds after suspension formation),
It is possible to maintain a uniform and stable suspension state without being dissolved in the carrier, so that the patient can easily ingest the active drug without feeling the bitter taste of the active drug itself.

DETAILED DESCRIPTION OF THE INVENTION The beads used in the present invention are formed by first pulverizing the active agent. Preferred active agents are approximately 20
It is potassium chloride powdered to 0 mesh. The wax or, preferably, a mixture of mono and diglycerides is dissolved in the molten state. Melting temperature of glyceride is about 60-80 ℃
Is. The active agent is then added to this molten mixture to 40-60% of the total amount.

Waxes and glycerides provide a taste masking coating over the active agent. According to the present invention, the respective densities of the flavor masking coating and the active agent are balanced, such as through selection of the active ingredient having the desired density.
For example, if the material forming the taste masking coating is a low density material, such as a wax or a monoglyceride or diglyceride, the low density material reduces the overall density of the taste masked active agent. On the other hand, dense materials such as calcium sulfate increase the overall density of the taste-masked active agent.

The density of the taste-masked active agent of the present invention should be equal to the density of the liquid carrier in which the active agent is suspended. That is, if the flavor-masked active agent is suspended in, for example, water, the overall density of the resulting mixture will be approximately 1. Also, the flavor masking coating: active agent ratio should be adjusted so that the solubility of the agent is reduced during the first 60 seconds. For example, the following composition may reduce the solubility of the drug.

Example 1 Active Agent 50% Mono and Diglycerides 25% Paraffin Wax 25% 100% Example 2 Active Agent 55% Mono and Diglycerides 40% Carnauba Wax 15% 100% Suitably, flavors, modifiers and / or air Add to the mixture. The mixture is then placed in a spinner from which liquid beads of the mixture are released, which solidifies while cooling. The beads are usually 30-100 mesh. These can be compressed into tablets.

The beadlets float on water because the flavor masking coating is hydrophobic. To make the mixture hydrophilic or improve workability, a surfactant or a surface modifier is added to the mixture. A preferred surfactant is sodium lauryl sulfate, which forms 0.25 to 2% by weight of the beadlets, preferably 1%. Surfactants can be added before or after spinning the beads.

Also, additional colorants and flavors can be added. Advantageously, an anti-cake forming agent such as silicon dioxide may be contained in 1 to 3% by weight of the beads. In addition, other materials can be incorporated into the beads that do not compromise the basic properties of the material. Initially reduces solubility but gastric acid pH
It is particularly desirable to add a pH adjusting agent that is neutralized with. This allows rapid dissolution in the stomach. As the pH adjusting agent, dicalcium phosphate or the like can be used, and examples of the composition containing the pH adjusting agent include the following.

Example 1 Active Agent 45% Mono and Diglyceride 40% Dicalcium Phosphate 15% 100% Example 2 Active Agent 40% Mono and Diglyceride 40% Magnesium Oxide 20% 100% The composition containing other pH regulators is as follows: Is.

Example 3 Active Agent 55% Mono and Diglycerides 40% Citric Acid 5% 100% Furthermore, another class of pH modifiers is used in the present invention such that the bead particles have a more or less effect on the pH of the physiological fluid. It can be, for example, the following composition including a pH adjusting agent.

Example 4 Active Agent 45% Mono and Diglycerides 40% Magnesium Oxide 15% 100% Beads can be packaged in a single dose package.
If the patient needs to take a single dose, the contents of the package are poured into a full glass of liquid. The beads form a suspension and do not dissolve immediately. However, within 15 minutes 90% dissolves very rapidly, preventing gastric ulcers and allowing the patient to drink the liquid.

The composition of the present invention has various advantages. First, the active agent can be taste masked in a solid dosage form.
Second, it can be administered in liquid form to patients who cannot take it in solid form. Thirdly, the side effects of solid dosage forms, such as intestinal ulcers, can be prevented. Such intestinal ulcers are more painful than gastric ulcers and often require more intense and long-term pharmaceutical treatment. Fourth, there is no gastric ulcer due to the rapid dissolution of the product. Fifth, it has succeeded in producing a consumer-acceptable pharmaceutical composition that satisfies the needs of patients when taking a drug, especially when a large dose is required. That is, when the administered drug has an unpleasant taste, or when a large amount of administration or a long-term administration is required, whether or not the patient accepts the prescribed drug treatment becomes a problem. The use of the taste-masked pharmaceutical composition of (1) can mask the unpleasant taste of the drug and can provide a suitable dosage form, thereby facilitating patient compliance.

(Examples) Next, the present invention will be described in more detail with reference to Examples, but the invention is not limited thereto.

Example 1 Anlubuterol sulfate / release control liquid A liquid having the following composition was produced.

Albuterol Sulfate 7.5% Hydrogenated vegetable oil 92.5% Fat base was dissolved and albuterol sulfate powder was added carefully. The resulting melt was solidified with a spinning disk or other suitable spray solidification equipment. The obtained beads were mixed with silicon dioxide and sodium lauryl sulfate to obtain a liquid having the following composition.

Albuterol sulphate beads 99.25% Silicon dioxide 0.25% Sodium lauryl sulphate 0.50% Example 2 Theophylline release controlling liquid A liquid having the following composition was produced.

Theophylline 40% Carnauba wax 60% Wax base was dissolved and theophylline powder was added carefully.

The resulting melt was solidified with a spinning disk or other suitable spray solidification equipment.

The obtained beads were mixed with silicon dioxide and sodium lauryl sulfate to obtain a liquid having the following composition.

Theophylline beads 99.25% Silicon dioxide 0.25% Sodium lauryl sulphate 0.50% Example 3 Antacid liquid The antacid liquid consists of three separate types with the following compositions.

Beads # 1 wt% Magnesium hydroxide 21.31 Aluminum hydroxide dry gel 24.03 Na Azulene sulfonate 0.19 NaCu Chlorophylline 0.21 Mono and diglycerides 26.40 Carnauba wax 26.40 Sodium lauryl sulphate 1.46 100.00 Beads # 2 Scopolia 10% extract 60.00 Mono and Diglyceride 39.90 FD & C Blue # 1 0.06 FD & C Yellow # 5 0.04 100.00 Beads # 3 NaCu Chlorophylline 33.00 Stearic acid 67.00 100.00 Carnauba wax, mono- and diglycerides and stearic acid were used as the base materials, these were melted and the active ingredient was carefully added. . The resulting melt was solidified with a spinning disk or other suitable spray solidification equipment.

 The obtained beads were mixed in the following ratio.

Bead # 1 13.5 parts Bead # 2 2.0 parts Bead # 3 1.0 parts The following materials were added to the above mixture and the whole mixture was remixed.

Silicon dioxide 0.50% Menthol flavor 0.40% Peppermint flavor 0.07% Sodium lauryl sulphate 0.50% Test Example 1 Solubility of composition The composition containing potassium chloride active agent of the present invention was tested and the following results were obtained.

5 minutes 83% 10 minutes 96% 15 minutes 99% 30 minutes 100% Test Example 2 In-vivo test of composition The pharmaceutical composition of the present invention was evaluated by several flavor test panelists, and the composition of the present invention was obtained. Has been proved to be extremely satisfactory, with the excellent effects described above.

Claims (20)

(57) [Claims] 1. A drug delivery composition comprising a flavor-masked solid active agent rendered hydrophilic, the density of which is about the same as the liquid carrier in which the active agent is suspended. 2. The composition of claim 1 which contains a flavor. 3. A composition according to claim 1, which contains a surfactant which promotes wettability. 4. The composition according to claim 1, which contains a pH adjusting agent. 5. The active agent is calcium chloride.
The composition as described. 6. A composition according to claim 1 wherein the active agent is taste masked by wax. 7. A composition according to claim 1 wherein the active agent is taste masked by a mixture of mono and diglycerides. 8. A composition according to claim 1, which contains a pH regulator which improves the physical / chemical stability of the composition. 9. A composition for drug delivery, comprising a flavor-masked solid active agent rendered hydrophilic.
Agent for administration to the tongue surface in the mouth of a human or animal, characterized in that the density of the active agent is about the same as the density of the liquid carrier in which the active agent is suspended, the liquid carrier being saliva A composition for delivery. 10. Hydrophilic beads consisting of a suspension in a liquid carrier, said beads comprising active agent, 0.25 to 2% by weight based on the total amount of said beads, wax, and wax.
A coating selected from the group consisting of monoglycerides, diglycerides and mixtures thereof, the density of the beads being approximately the same as the density of the liquid carrier, whereby the active agent is It does not substantially dissolve in the liquid carrier until after about 60 seconds,
As a result, a liquid characterized by the inability to taste the active agent when ingested the pharmaceutical composition and that about 90% or more of the active agent dissolves within about 15 minutes after suspension formation. Shape-masking pharmaceutical composition. 11. The active agent is calcium chloride.
11. The pharmaceutical composition according to 10. 12. The pharmaceutical composition according to claim 10, wherein the beads further comprise 1-3% by weight of anti-cake forming agent. 13. The pharmaceutical composition according to claim 12, wherein the anti-cake forming agent is silicon dioxide. 14. The pharmaceutical composition according to claim 10, wherein the beads further contain one or more substances selected from the group consisting of flavors, colorants and pH adjusting agents. 15. Hydrophilic beads consisting of a suspension in water, the beads comprising an active agent, 0.25 to 2% by weight, based on the total amount of the beads, of sodium lauryl sulphate surfactant, a wax, A coating selected from the group consisting of monoglycerides, diglycerides and mixtures thereof, the density of the beads being approximately the same as the density of water, so that the active agent has a concentration of about 60 after formation of the suspension. It does not substantially dissolve in water until after a second, resulting in the inability to taste the active agent upon ingestion of the pharmaceutical composition, and about 90% or more of the active agent after suspension formation. A flavor-masked pharmaceutical composition in liquid form, which dissolves within about 15 minutes. 16. The active agent is calcium chloride.
16. The pharmaceutical composition according to 15, wherein 17. The pharmaceutical composition according to claim 15, wherein the beads further comprise 1-3% by weight of an anti-cake forming agent. 18. The pharmaceutical composition according to claim 17, wherein the anti-cake forming agent is silicon dioxide. 19. The pharmaceutical composition according to claim 15, wherein the beads further comprise one or more substances selected from the group consisting of flavors, colorants and pH modifiers. 20. Hydrophilic beads comprising an active agent, 0.25-2% by weight based on the total amount of the beads, a wax, and a wax.
A coating selected from the group consisting of monoglycerides, diglycerides and mixtures thereof, the density of the beads being approximately the same as the density of the liquid carrier, whereby the active agent is It does not substantially dissolve in the liquid carrier until after about 60 seconds,
As a result, the inability to taste the active agent when ingested the pharmaceutical composition, and about 90% or more of the active agent are characterized by dissolution within about 15 minutes after suspension formation, Hydrophilic beads for making a pharmaceutical suspension suspended in a liquid carrier.