KR101746500B1 - Loratadine composition for soft capsule formulation and soft capsule containing the same - Google Patents

Abstract

The present invention relates to a loratadine composition for soft capsule preparation having excellent dissolution rate and quick-release stability, and a loratadine-containing soft capsule containing the same.

Description

TECHNICAL FIELD [0001] The present invention relates to a loratadine composition for soft capsule preparation, and a soft capsule containing the same. BACKGROUND OF THE INVENTION [0002]

The present invention relates to a loratadine composition for soft capsule preparation having excellent dissolution rate and quick-release stability, and a loratadine-containing soft capsule containing the same.

Histamine can be classified into four types of histamine that act on the receptors of H-1, H-2, H-3 and H-4, respectively. Of these, H-1 receptors are involved in bronchoconstriction, vascular endothelial cell shrinkage, and vasodilatation, resulting in allergic rhinitis, asthma, atopic dermatitis, and urticaria. When an antihistamine acts on the H-1 receptor and converts the receptor to an inactive form, it may play a role of alleviating the various symptoms listed above.

Lauratadine is a second-generation antihistamine, and its structural formula is Ethyl 4- (8-chloro-5,6-dihydro-11H-benzo [5,6] cyclohepta- [ 1,2-b] pyridine-11-ylidene) -1-piperidinecarboxylate. Lauretadine has an activity of selectively inhibiting the H-1 receptor and is mainly used for allergic diseases. First-generation antihistamines cause side effects such as drowsiness, but second-generation antihistamines are used more often because they have fewer side effects than the first-generation antihistamines and have more excellent effects.

Tablets, as an oral dosage form such as a capsule, a syrup containing as a main component such loratadine may include Schering-Plough's ^{Claritin ®, Claritin Reditabs ®, Claritin} -D 24-Hour ® sold commercially. These products are described in detail in U.S. Patent Nos. 4,282,223, 4,659,716, 4,863,931, and 6,132,758.

In particular, soft capsules have been used for rapid absorption of loratadine in vivo. Generally, soft capsules are formulations in which one or more active ingredients are packed in a gelatin capsule in a liquid or slurry state. The coating of the soft capsule used herein is composed of gelatin, one or more plasticizers, water, etc., and if necessary, a coloring agent, a flavoring agent, an antiseptic, an opacifying agent and the like are added. For example, Korean Patent Application No. 2003-0013309 discloses a plasticizer composition for preventing blooming and a coating containing the same.

Gelatin used in the capsule of soft capsules is a substance obtained by hydrolyzing collagen, and has a polymer structure in which polypeptide chains are entangled. When gelatin alone is used in the capsule of the soft capsule, since the elasticity is not formed, a problem of breaking after molding occurs. Generally, a certain amount of plasticizer is added to control the hardness of the capsule. Plasticizers are used to impart moisturizing effects to soft capsules, examples of which include glycerin and sorbitol. When a large amount of glycerin is used as a plasticizer, the water content of the coating increases, the outer shape of the capsule changes, and the main component of the filler is transferred to the coating, resulting in disintegration. When a large amount of sorbitol is used as a plasticizer, sorbitol precipitates outside the coating film, causing a blooming phenomenon that turns white.

International application WO 2003/101378 discloses a soft capsule filling comprising triglyceride heavy chain fatty acids, one or more solubilizing agents, and an emulsifying agent. In addition, U.S. Patent No. 6,720,002 discloses a soft capsule filling comprising a lipophilic solvent, a dispersant, and a surfactant comprising mono- and di-glyceride heavy chain fatty acids, and in the case of a composition using a hydrophilic solvent, lauratadine precipitates .

When the soft capsule filler is prepared using only a fat-soluble solvent as described above, it can be formulated stable, but has a problem of low dissolution rate and bioavailability. In addition, when a soft capsule filling material is prepared using a hydrophilic solvent and a surfactant without using a fat-soluble solvent, the stability of the filling material itself is good, but when the soft capsule is molded, the moisture of the coating moves to the filling material, There is a drawback that precipitation occurs. Accordingly, there is a need to develop a loratadine composition which improves the stability of the soft capsule filling containing loratadine, the dissolution rate and the bioavailability.

When a fat soluble solvent is used alone as a solvent for a soft capsule filling, the dissolution rate and bioavailability are low, and when a hydrophilic solvent is used alone, crystals of loratadine precipitate. When they are simply mixed, they are not mixed well, It has been necessary to develop a loratadine composition for a soft capsule preparation that is stable in composition without layer separation or precipitation while using a hydrophilic solvent and a hydrophilic solvent.

Accordingly, the present invention provides a loratadine composition for a soft capsule preparation which is stable and hardly separated from a layer while using a fat soluble solvent and a hydrophilic solvent at the same time, and a soft capsule containing the loratadine composition.

However, the problems to be solved by the present invention are not limited to the above-mentioned problems, and other problems not mentioned can be clearly understood by those skilled in the art from the following description.

The first aspect of the present application relates to a pharmaceutical composition comprising as an active ingredient loratadine; Hydrophilic solvents; Fatty acid mono-, di-, tri-glycerides, and combinations thereof; And a loratadine composition for a soft capsule preparation comprising a dispersant or a surfactant.

According to one embodiment of the present invention, the loratadine may be contained in an amount of 6.6 to 10.0% by weight based on the weight of the total composition.

According to one embodiment of the present invention, the hydrophilic solvent may be contained in an amount of 6.9 to 41.2 wt% based on the weight of the total composition.

According to one embodiment of the invention, the hydrophilic solvent may be selected from the group consisting of polyethylene glycol, propylene glycol, polyethylene glycol esters of tetrahydrofurfuryl alcohol, and combinations thereof.

According to one embodiment of the present invention, the fat-soluble solvent may be contained in an amount of 41.1 to 76.2 wt% based on the weight of the total composition.

According to one embodiment of the present application, the oil-soluble solvent is selected from the group consisting of glycerol monocaprylocaprate (Imwitor 742), glyceryl monocaprate (Imwitor 308), glyceryl dicaprate, Propylene glycol monocaprylate (CAPRYOL ™ 90), propylene glycol caprylate (CAPRYOL ™ PGMC), propylene glycol laurate (LAUROGLYCOL ™ FCC), propylene glycol monolaurate (propylene glycol monolaurate) glycol monolaurate (LAUROGLYCOL ™ 90), glyceryl tricaprylate / caprate, glycerol caprylate / caprate, caprylic / capric triglyceride (Miglyol 812), and combinations thereof.

According to one embodiment of the present invention, when the loratadine composition comprises a dispersant, the dispersant may be contained in an amount of 6.2 to 6.4 wt% based on the weight of the total composition.

According to one embodiment of the disclosure, the dispersant may comprise povidone.

According to an embodiment of the present invention, the K value of the povidone may be from 17 to 30.

According to one embodiment of the present invention, when the loratadine composition comprises a surfactant, the surfactant may be contained in an amount of 1.9 to 10.0 wt% based on the weight of the total composition.

According to one embodiment of the invention, the surfactant may comprise a sorbitan fatty acid ester.

A second aspect of the present invention provides a loratadine-containing soft capsule comprising a loratadine composition according to the first aspect of the present disclosure.

The above-described task solution is merely exemplary and should not be construed as limiting the present invention. In addition to the exemplary implementations described above, there may be additional implementations and embodiments described in the drawings and detailed description of the invention.

The loratadine composition for a soft capsule preparation of the present application is excellent in dissolution rate and quick effect because it contains a hydrophilic solvent in addition to a fat soluble solvent and can be used as a lauratadine as a fat soluble solvent, Or the surfactant is mixed at a specific ratio, so that the layer separation and the precipitation of loratadine do not occur well and are stable.

1 is a graph comparing dissolution rates of a loratadine-containing soft capsule prepared according to one embodiment of the present invention and a control group.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily carry out the present invention. It should be understood, however, that the present invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In the drawings, the same reference numbers are used throughout the specification to refer to the same or like parts.

Throughout this specification, when an element is referred to as "including " an element, it is understood that the element may include other elements as well, without departing from the other elements unless specifically stated otherwise.

The terms "about "," substantially ", etc. used to the extent that they are used throughout the specification are intended to be taken to mean the approximation of the manufacturing and material tolerances inherent in the stated sense, Accurate or absolute numbers are used to help prevent unauthorized exploitation by unauthorized intruders of the referenced disclosure. The word " step (or step) "or" step "used to the extent that it is used throughout the specification does not mean" step for.

Throughout this specification, the term "combination thereof" included in the expression of the machine form means one or more combinations or combinations selected from the group consisting of the constituents described in the expression of the machine form, And the like.

Throughout this specification, the description of "A and / or B" means "A, B, or A and B".

Hereinafter, the loratadine composition for soft capsule preparation of the present invention and the loratadine-containing soft capsule containing the same will be described in detail with reference to the embodiments and examples and the drawings. However, the present invention is not limited to these embodiments and examples and drawings.

The first aspect of the present application relates to a pharmaceutical composition comprising as an active ingredient loratadine; Hydrophilic solvents; Fatty acid mono-, di-, tri-glycerides, and combinations thereof; And a loratadine composition for a soft capsule preparation comprising a dispersant or a surfactant.

When a hydrophilic solvent is used alone as a loratadine composition for a soft capsule preparation, loratadine can be precipitated when packed in a soft capsule, and when a fat-soluble solvent such as a medium chain fatty acid mono-, di-, or tri-glyceride is used alone, the dissolution rate and bioavailability Therefore, the loratadine composition for the soft capsule preparation of the present application is prepared by mixing a hydrophilic solvent such as a medium-chain fatty acid mono-, di-, tri-glyceride and a hydrophilic solvent, using a dispersant or a surfactant, A composition having the characteristics of spontaneous emulsification to be dispersed was prepared.

When the dispersing agent and the surfactant are used together, the dispersing agent may be precipitated in the soft capsule and stored in the refrigerator. Therefore, it may be preferable to use only one kind of dispersing agent or surfactant.

According to one embodiment of the present invention, the lauratadine may be included in the composition in an amount of 6.6 to 10.0% by weight, but may not be limited thereto.

According to one embodiment of the present invention, the hydrophilic solvent may include, but is not limited to, 6.9 to 41.2% by weight of the total composition.

According to one embodiment of the present invention, the hydrophilic solvent may be selected from the group consisting of polyethylene glycol (Polyethyleneglycol 400 and / or Polyethyleneglycol 600), propylene glycol, polyethylene glycol esters of tetrahydrofurfuryl alcohol, and combinations thereof, But may not be limited thereto.

According to one embodiment of the present invention, the fat-soluble solvent may include, but is not limited to, 41.1 to 76.2 wt% based on the weight of the total composition.

When the ratio of the oil-soluble solvent is higher, the soft capsules show good properties when filled, but when water is added, the layer separation may occur. This is because, when the loratadine composition is filled in the soft capsule, the hydrophilic solvent contained in the composition reacts with the capsule of the soft capsule, and the moisture of the capsule is attracted toward the packing.

When the ratio of the oil-soluble solvent is lower or not at all, the properties of the composition itself are good at room temperature and refrigeration. However, when the soft capsule is filled, the moisture of the coating moves to the filler, Stability can be deteriorated because this crystal can be precipitated.

According to one embodiment of the present application, the oil-soluble solvent is selected from the group consisting of glycerol monocaprylocaprate (mono & diglyceride) (Imwitor 742), glyceryl monocaprate (Imwitor 308), glyceryl dicaprate ), Propylene glycol monocaprylate (CAPRYOL ^TM 90), propylene glycol caprylate (CAPRYOL ^TM PGMC), propylene glycol laurate (LAUROGLYCOL ^TM FCC), propylene glycol monolaurate (LAUROGLYCOL ^TM Glyceryl tricaprylate / caprate, glycerol caprylate / caprate, caprylic / capric triglyceride (Miglyol 812), glycerol / capric triglyceride ), And combinations thereof. However, the present invention is not limited thereto.

According to one embodiment of the present invention, when the loratadine composition comprises a dispersant, the dispersant may include, but is not limited to, 6.2 to 6.4 wt% based on the weight of the total composition.

According to one embodiment of the present disclosure, the dispersant may include, but is not limited to, povidone.

According to one embodiment of the invention, the K value of the povidone (a function of the intrinsic viscosity and degree of polymerization of the polymer) may be from 17 to 30, but is not limited thereto. When the K value of povidone is lower than the above range, the viscosity is low and it can be precipitated in the refrigerator.

According to one embodiment of the present invention, when the loratadine composition includes a surfactant, the surfactant may be contained in an amount of 1.9 to 10.0 wt% based on the weight of the total composition, but may not be limited thereto.

According to one embodiment of the present invention, the surfactant may include a sorbitan fatty acid ester, and the sorbitan fatty acid ester may have a hydrophilic lipophilic balance (HLB) value of 14 to 16, but the present invention is not limited thereto. For example, the sorbitan fatty acid ester may be selected from the group consisting of sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate, Polysorbate (Tween) 20 , Polysorbate 40, polysorbate 60, polysorbate 80, polysorbate 120, ethoxylated aliphatic alcohols (Oleth-20), capylocaproyl macrogol-8 glycerides (LAUOGLYCOL ^TM 90), and combinations thereof. The term " a "

For example, the loratadine composition for the soft capsule formulation herein may comprise, but is not limited to, water of up to 5.6 wt%, for example, 4.8 to 5.6 wt%, based on the weight of the total composition. If the water is contained in excess of the above range, since the water moves from the composition to the capsule of the capsule, the drying time is long and the shape of the capsule may change.

A second aspect of the present invention provides a loratadine-containing soft capsule comprising a loratadine composition according to the first aspect of the present disclosure.

For example, gelatin having a large reactive group (-COOH, -NH ₂ , -SH, -OH) in the polypeptide chain may be used as a main component of the soft capsule, but the present invention is not limited thereto . The functional group can be introduced into the raw material by acid or alkali treatment, or by treating the functional group with succinic acid. As the film of the soft capsule of the present invention, gelatin having been subjected to acid treatment may be used, but it may not be limited thereto. The method for producing the soft capsule can be employed by those skilled in the art without limitation, from those methods commonly used in the art for the production of soft capsules.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[Example]

1. Preparation of loratadine composition for soft capsule preparation and characterization

(Imwitor 742) and a hydrophilic solvent (polyethylene glycol, PEG) according to the composition of the present invention in order to observe the properties of the loratadine composition in the composition state before administration to the capsules The loratadine composition for soft capsule preparation of Rx1 and Rx2 and the loratadine composition for soft capsule preparation of Comparative Example 1 (Rx3) containing relatively less fat-soluble solvent were prepared with the compositions shown in Table 1 below.

Specifically, in the case of Examples Rx1 and Rx2, Imwitor 742, PEG 400, and water were added and heated to 60 DEG C, followed by lauratadine and povidone, respectively, in turn to dissolve them. The dissolved contents were cooled to room temperature, filtered through 200 mesh, and depressurized to 640 mmHg to prepare a loratadine composition. In the case of Comparative Example 1 (Rx3), Imwitor 742, PEG 400, Tween 80, and water were added, and the mixture was heated to 60 ° C and then lauratadine was added thereto to dissolve all. The dissolved contents were cooled to room temperature, filtered through 200 mesh, and depressurized to 640 mmHg to prepare a loratadine composition.

The prepared loratadine compositions were stored at room temperature and in a refrigerator for 14 days. As a result, both Examples Rx1 and Rx2 and Comparative Example 1 showed good properties at room temperature and refrigeration conditions (Table 1).

Next, a loratadine composition for soft capsule preparation of Comparative Example 2 (Rx4) using only polyethylene glycol (PEG) and propylene glycol (PG) as a hydrophilic solvent without a fat soluble solvent was prepared with the composition shown in Table 2 below.

Specifically, PEG 400, propylene glycol, Tween 80 were mixed at room temperature. Subsequently, the mixture was gradually warmed to 60 DEG C, and then Cremophor RH40 and loratadine were dissolved in succession. The completely dissolved mixture was cooled to room temperature, filtered at 200 mesh, and defoamed at 640 mmHg.

The prepared loratadine composition was stored at room temperature and in a refrigerator for 14 days. As a result, Comparative Example 2 showed satisfactory properties at both room temperature and refrigeration conditions (Table 2).

2. Preparation of loratadine-containing soft capsules

(La 2 O 3) and a hydrophilic solvent (PEG (hydrophilic solvent)) in accordance with the compositions shown in Tables 3 and 4, and a loratadine composition for soft capsule preparation of Examples Rx5 and Rx6 containing a lipid soluble solvent (Imwitor 742) and a hydrophilic solvent And PG) of Comparative Examples 3 and 4 were prepared, and loratadine-containing soft capsules containing the same were prepared.

For the preparation of soft capsules, the film was made into a thin and wide ribbon, and then two ribbons and a composition were put in between the molds to be molded. The coating film used herein was formed using gelatin, water and a plasticizer, and sorbitol (POLYSORB 85/70/00) was used as the plasticizer. Gelatin was used in an amount of 58.4 wt% based on the weight of the film, 8.0 wt% of water, and 33.5 wt% of POLYSORB 85/70/00, and 0.1 wt% of a colorant was used. Unless otherwise described, all of the examples were molded into soft capsules of the same size using coatings of the same composition. The capsule size unit "minim" is one of the volume units of liquid, and 1 minim is equal to 0.0616 mL.

Further, according to the composition shown in Table 5 below, a soft capsule was prepared by preparing a loratadine composition for a soft capsule preparation using a lipid soluble solvent (Imwitor 742) and a hydrophilic solvent (PEG).

For the preparation of the loratadine composition, Imwitor 742, PEG 400 and water were added and the mixture was heated to 60 DEG C and then lauratadine was added thereto to dissolve completely. The dissolved mixture was cooled to room temperature, and Tween 80 was added thereto. When mixing was complete, the mixture was filtered through 200 mesh and defoamed to 640 mmHg. The completed loratadine composition was made into soft capsules.

3. Change in content of loratadine composition for soft capsule preparation

(Imwitor 742) with a hydrophilic solvent (PEG) in comparison with the composition of the present invention in order to confirm whether there is a change in the content of lauratadine, which is the main component, depending on the presence or absence of the oil soluble solvent (Imwitor 742) Comparative Example 3 (Rx7) and Comparative Example 4 (Rx8) containing only hydrophilic solvents PEG and PG without oil-soluble solvent were observed and the changes in the content of the lauratadine compositions according to the conditions were observed.

For the test, the contents prepared in Comparative Example 3 (Rx7) and Comparative Example 4 (Rx8) were stored in a transparent polyethylene (PE) bottle and then placed in a room temperature (25 DEG C, 60% RH) and refrigerated (5 DEG C) Respectively. The content test was based on the content test of USP 'Loratadine Tablets'.

As a result, no change in the content of loratadine was observed, even if the ratio of the oil-soluble solvent was small or the oil-soluble solvent was not used.

7. Stability test according to use of surfactant and dispersant

To compare the properties of a loratadine composition comprising both the present loratadine composition comprising only one dispersant or a surfactant and a dispersant and a surfactant, a soft capsule containing a loratadine composition of Example Rx5 and a soft capsule containing a surfactant of Example Rx5 The properties of Comparative Examples 5 to 7 (Rx 12 to 14) prepared by adding Tween 80 as a surfactant to the lauratadine composition were observed and the results are shown in Table 7.

To prepare the lauratadine composition of Example Rx5, Imwitor 742, PEG 400, and water were added and heated to 60 DEG C, followed by lauratadine and povidone, respectively, in turn to dissolve them. The dissolved contents were cooled to room temperature, filtered through 200 mesh, and depressurized to 640 mmHg to prepare a loratadine composition. To prepare the loratadine compositions of Comparative Examples 5 to 7, Imwitor 742, PEG 400, Tween 80, and water were added and heated to 60 ° C, followed by lauratadine and povidone, respectively, in turn to dissolve them. The dissolved contents were cooled to room temperature, filtered through 200 mesh, and depressurized to 640 mmHg to prepare a loratadine composition. The prepared composition was placed in a polyethylene bottle and stored for 84 days at room temperature, refrigeration and accelerated conditions, and the properties thereof were observed. The composition was uniformly injected into a blank capsule and stored for 14 days at room temperature, refrigeration and acceleration conditions.

As a result of the test, Example Rx5 showed good properties at room temperature, refrigeration and accelerating conditions even after 84 days, and opacity was observed only in the accelerated condition after 14 days from the injection into the capsule. In Comparative Examples 5 to 7, white band formation was observed during refrigerated storage for 84 days, and opacity was observed under refrigeration and acceleration or accelerated conditions 14 days after being introduced into capsules (Table 7).

From these results, it can be confirmed that when the loratadine composition contains both a dispersant and a surfactant, the stability is lowered when soft encapsulated, while the stability is relatively high when only a dispersant is used.

Next, properties of Example Rx15, Example Rx16, and Example Rx17 in which Tween 80, a surfactant, were added to the lauratadine composition of Example Rx5, except for the dispersant povidone, were observed over time and the results are shown in Table 8 Respectively.

For the preparation of the loratadine composition, Imwitor 742, PEG 400, Tween 80, and water were added, heated to 60 ° C, and lauratadine was added to dissolve them all. The dissolved contents were cooled to room temperature, filtered through 200 mesh, and depressurized to 640 mmHg to prepare a loratadine composition. The prepared composition was placed in a polyethylene bottle and stored for 84 days at room temperature, refrigeration and accelerated conditions, and the properties thereof were observed. The composition was uniformly injected into a blank capsule and stored for 14 days at room temperature, refrigeration and acceleration conditions.

As a result of the test, Examples Rx15 and Rx16 showed good properties at room temperature, refrigeration and acceleration conditions even after 84 days, and showed good properties even after 14 days of capsule injection. In Example Rx17, white band formation was observed during refrigerated storage for 84 days, but good characteristics were obtained even after 14 days of being added to capsules (Table 8).

From these results, it was confirmed that the loratadine composition was stable in the capsules even when a surfactant alone was used instead of the dispersant.

Next, Twain 80, a surfactant, was added to the lauratadine composition of Example Rx6 except for povidone as a dispersant, and the composition of the oil-soluble solvent and hydrophilic solvent was changed to Comparative Example 11 (Rx21), The properties of Comparative Example 12 (Rx22) and Comparative Example 13 (Rx23) over time were observed, and the results are shown in Table 9.

For the preparation of the loratadine composition, Imwitor 742, PEG 400, Tween 80 and water were added and heated to 60 ° C, followed by lauratadine and povidone, respectively, in turn to dissolve them. The molten mixture was cooled to room temperature, filtered at 200 mesh, and defoamed at a pressure of 640 mmHg. The prepared composition was placed in a polyethylene bottle and stored for 84 days at room temperature, refrigeration and accelerated conditions, and the properties thereof were observed. The composition was uniformly injected into a blank capsule and stored for 14 days at room temperature, refrigeration and acceleration conditions.

As a result of the test, in Comparative Examples 11 to 13, crystals were formed at room temperature when stored for 84 days, and white bands were observed under refrigerated conditions. In addition, in Comparative Examples 11 to 13, layer separation was observed under refrigerated and accelerated conditions 14 days after the capsules were added (Table 9).

Therefore, even when only one type of surfactant or dispersant is used, when a composition of a hydrophobic solvent and a lipophilic solvent different from the lauratine composition of the present invention is adopted, crystals are formed upon introduction into the capsule and layer separation occurs. Respectively.

4. Stability test of loratadine-containing soft capsules

The soft capsules prepared to contain the compositions of Examples Rx5 and Example Rx6 and Comparative Examples 3 (Rx7) and Comparative Example 4 (Rx8) were stored at room temperature for 47 days, and the crystal precipitation was confirmed and shown in Table 11 . Comparative Example 4 was further divided into Comparative Examples 4-1 and 4-2 according to the composition of the soft capsule coating. Claritin ^® Liqui-Gels ^® was used as a control.

As a result of the test, in Example Rx5 and Example Rx6, a transparent liquid state was maintained even after storage at room temperature for 47 days, and crystals were not observed. However, in Comparative Example 3, it was observed that crystals were formed after 40 days (Table 10).

The soft capsules prepared to contain the compositions of Examples Rx5 and Example Rx6, and Comparative Examples 4-1 and 4-2, in which no crystals were produced in the above experiment, After storing in a Petri dish for 40 days, the presence of crystal precipitation was confirmed and is shown in Table 11.

As a result of the test, Rx5 and Rx6 of Example Rx5 remained transparent without being determined even after storage for 40 days in a brown bottle at 30 DEG C and 75% RH. When stored in a Petri dish, layer separation was performed after 28 days and 15 days, respectively But no crystals were formed. On the other hand, in Comparative Example 4-1, crystals were formed in 5 days in both brown bottle and petri dish when stored at 30 ° C and 75% RH, and in Comparative Example 4-2, (Table 11).

Next, the contents of the soft capsules prepared according to Example Rx24 and Example Rx25 were stored in a brown bottle or a Petri dish at a temperature of 30 DEG C and 75% RH for 53 days to confirm whether or not the crystals were precipitated.

As a result of the test, both Example Rx24 and Example Rx25 retained transparency even after storage at 30 ° C and 75% RH for 53 days, and crystals were not formed (Table 12).

5. Changes in Properties of Lauratadine Composition with Water Addition

Although the lauratine composition itself is stable, crystallization may occur as the water component of the coating moves into the composition when it is molded into a soft capsule form. Therefore, in order to examine whether the water component of the coating film can maintain a stable property even if the water component of the coating film moves during the molding of the soft capsule, water is added to the loratadine composition at a certain ratio, and then the composition change of the composition is observed.

Specifically, Example A according to the composition of the present invention and Comparative Example 14 (Rx9) containing no hydrophilic solvent, unlike the composition of the present invention, and Comparative Example 15 (Rx 10) containing both a dispersant and a surfactant were produced And the properties of these materials were compared under various conditions.

 For Example A, Imwitor 742, PEG 400 and water were mixed at room temperature. Subsequently, the mixture was slowly heated to 60 DEG C, and povidone and loratadine were respectively added in turn to dissolve. The completely dissolved contents were cooled to room temperature and then filtered at 200 mesh and defoamed at 640 mmHg. In the case of Comparative Example 14 (Rx 9), Imwitor 742 was gradually heated to 60 ° C, and povidone and loratadine were respectively added and dissolved in turn. The completely dissolved contents were cooled to room temperature and then filtered at 200 mesh and defoamed at 640 mmHg. Comparative Example 15 (Rx10) In the case of Imwitor742, PEG 400, Tween 80 and water were mixed at room temperature. Subsequently, the mixture was slowly heated to 60 DEG C, and povidone and loratadine were respectively added in turn to dissolve. The completely dissolved contents were cooled to room temperature and then filtered at 200 mesh and defoamed at 640 mmHg.

Water was added to the compositions of Example A, Comparative Example 14, and Comparative Example 15 under various conditions and mixed. The mixture was allowed to stand at room temperature to observe changes in the properties thereof.

As a result of the test, Example A showed transparency for 1 hour to 1 day when 5.0%, 7.0% and 9.0% of water were administered, and when 15.0% of water was administered, it became opaque on leaving for one day. Respectively. In Comparative Examples 14 and 15, opaque properties were observed when water was administered at 9.0% for 1 hour. When water was administered at 15.0%, opacity became clear during daytime and layer separation was observed (Table 13).

6. Elution test of loratadine-containing soft capsules

The soft capsules prepared according to Examples Rx5 and Example Rx6 were subjected to a dissolution test according to USP 'Loratadine Tablets', and the results are shown in Table 14. The test was carried out at 50 rpm in the second method (paddle) and 900 ml of water at 37 ° C. The eluted test liquid was analyzed at 272 nm using UV. As a result, the loratadine in accordance with the present invention was found to show a faster dissolution rate when compared to the soft capsule containing a commercially available Claritin ^®.

Next, the soft capsules of Example Rx24 and Example Rx25 were used to conduct a dissolution test according to USP 'Loratadine Tablets', and the results are shown in Table 15. [ Claritin ^® Liqui-Gels ^® was used as a control. The test was carried out at 50 rpm in the second method (paddle) and 900 ml at 37 ° C in the eluent. The eluted test liquid was analyzed at 272 nm using UV.

The test results, confirms that the call has shown over 80% in 30 minutes fast 15 minutes the dissolution rate compared to the control group of Claritin ^® whereas inde two hours showed over 80% dissolution 45 minutes embodiment Rx24 and capsules of Example Rx25 is Claritin ^® (Table 15). This implies that the loratadine-containing capsules according to the embodiments of the present invention are able to absorb in the body faster than conventional products (Fig. 1).

It will be understood by those of ordinary skill in the art that the foregoing description of the embodiments is for illustrative purposes and that those skilled in the art can easily modify the invention without departing from the spirit or essential characteristics thereof. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed in a similar fashion may also be implemented.

The scope of the present invention is defined by the appended claims rather than the detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included within the scope of the present invention.

Claims (12)

From 6.6 to 10.0% by weight of lauratadine as an active ingredient;
6.9 to 41.2% by weight polyethylene glycol 400 based on the weight of the total composition;
From 41.1 to 76.2% by weight, based on the weight of the total composition of glycerol monocaprylocaprate;
6.2 to 6.4 wt% of povidone or 1.9 to 10.0 wt% of sorbitan fatty acid ester based on the weight of the total composition; And
By weight, based on the weight of the total composition, of water,
A loratadine composition for soft capsule preparation. delete A loratadine-containing soft capsule comprising the loratadine composition of claim 1. delete delete delete delete delete delete delete delete delete

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