WO2015170939A1 - Pharmaceutical preparation for masked taste oral administration, containing clomipramine - Google Patents

Abstract

The present invention relates to: a pharmaceutical preparation for oral administration, containing, as active ingredients, clomipramine or a pharmaceutically acceptable salt thereof, and a cation exchange resin and an anionic polymer as taste masking agents; and a preparation method therefor, wherein the pharmaceutical preparation can be orally administered even while containing a pharmaceutically effective amount of clomipramine since the specific taste of clomipramine, particularly, all of the bitter taste, spicy taste and sharp taste are effectively masked, and thus the convenience of drug administration and portability is improved.

Description

Pharmaceutical preparations for taste masking oral administration containing clomipramine

The present invention relates to a pharmaceutical preparation comprising clomipramine or a pharmaceutically acceptable salt thereof as an active ingredient. More specifically, clomipramine-specific tastes, particularly bitter, spicy and arine tastes are all effectively shielded and contain a pharmaceutically effective amount of clomipramine and can be administered orally, thereby ensuring ease of taking It relates to a pharmaceutical preparation for oral administration using a pramin or a pharmaceutically acceptable salt thereof as an active ingredient, and a preparation method thereof.

This application claims the priority based on Korean Patent Application No. 10-2014-0054970 filed on May 8, 2014 and Korean Patent Application No. 10-2015-0064918 filed on May 8, 2015, All content disclosed in the specification and drawings of an application is incorporated in this application.

Clomipramine is a type of selective serotonin reuptake inhibitor (SSRI).

Clomipramine is a representative tricyclic antidepressants (TCAs) and is also used as a treatment for premature ejaculation (product name: Annafranil). The diagnostic criterion for premature ejaculation is DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision), which by definition defines premature ejaculation on a continuous, repetitive basis, with minimal sexual stimulation. When inserted, it is the situation immediately after insertion.

Clomipramine may be administered in the blood, but an oral dosage form is preferable in view of the condition in which premature ejaculation treatment and / or antidepressant is used, and the convenience of carrying and taking due to the nature of the disease. In addition, clomipramine hydrochloride is commercially available in tablets containing 10 mg, 15 mg, 25 mg, 50 mg or 75 mg, and a small amount of administration is reported to have little therapeutic effect unlike placebo, for example, to treat effective OCD. 250 mg of clomipramine hydrochloride is recommended daily for a single dose. However, clomipramine hydrochloride has a characteristic bitter taste and spicy and arine taste, which not only cause discomfort during oral administration but also cause local paralysis symptoms in the oral cavity. Oral dispersible formulations in which the taste is directly felt, such as oral soluble films, oral disintegrating tablets, suspensions, suspension tablets, fast disintegrating tablets, oral disintegrating capsules, oral disintegrating granules, oral disintegrating troches, sublingual tablets, It is not easy to prepare powders and / or chewable tablets.

More specifically, the reason why the formulation for oral administration containing clomipramine hydrochloride as an active ingredient is limited is as follows.

Clomipramine hydrochloride, along with its characteristic bitter taste, has a strong spicy and astringent taste, as well as a symptom of tongue paralysis.

First, in order to mask the unique taste due to clomipramine hydrochloride (Taste Masking, TM) and to predict the absorption pattern (eg, Cmax, Tmax), a considerable amount of taste masking agent (Taste Masking Agent) ) And the amount of coating is inevitably required, resulting in an increase in loading weight in the formulation.

Second, in order to load a high dose of TM agent in a formulation of limited size, the amount of addition of clomipramine hydrochloride and other additives is limited, in which case satisfactory activity, physical properties and handleability It is not easy to prepare a formulation with.

Third, in order to prepare clomipramine hydrochloride into a film formulation, it is necessary to use a certain amount of polymer to maintain the shape of the film. However, in order to load a considerable amount of the taste masking agent (Taste Masking Agent) and the coating amount in a limited size film, the amount of the polymer is very small. If the amount of polymer is not sufficient, the formed film is difficult to have suitable physical properties for handling (eg, flexibility, tensile force).

Finally, the biggest problem is the use of TM masks (Taste Masking Agents), which are commonly used to mask the taste of pharmaceutical preparations, although masking of the bitter and spicy tastes caused by clomipramine hydrochloride is possible. It is impossible to completely mask all the unpleasant tastes.

Therefore, the problem to be solved by the present invention is to provide a pharmaceutical preparation for oral administration and a method for preparing the same effective for oral administration by effectively masking all the unpleasant taste caused by clomipramine hydrochloride in a small amount (Taste Masking).

In order to solve the above technical problem, in one aspect the present invention comprises a clomipramine or a pharmaceutically acceptable salt thereof as an active ingredient, together with a cation exchange resin and an anionic polymer as a taste masking agent (Taste Masking Agent) It provides a pharmaceutical formulation comprising oral administration and a method for producing the same.

More specifically, in one embodiment, the present invention includes clomipramine or a pharmaceutically acceptable salt thereof as an active ingredient, and includes oral administration including a cation exchange resin and an anionic polymer as a taste masking agent. Provide a pharmaceutical formulation.

The present invention confirms that the combination of the cation exchange resin and the anionic polymer produces a synergistic effect and is very effective in masking the unique taste of clomipramine (particularly clomipramine hydrochloride) in a small amount. Completed.

The pharmaceutical preparations according to the invention may comprise clomipramine derivatives in place of or in combination with clomipramine as an active ingredient. Therefore, the pharmaceutical preparations according to the present invention may include derivatives having pharmaceutical activity equivalent to clomipramine.

In the present invention, the term 'clomipramine' includes a free base or a pharmaceutically acceptable salt.

In the present invention, a 'pharmaceutically acceptable salt' is a concentration that is relatively nontoxic and harmless to the patient, and any organic or inorganic side effects caused by this salt do not degrade the beneficial efficacy of clomipramine. As an addition salt, for example, organic acids, inorganic acids or non-toxic salts can be used as the free acid, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. can be used as the inorganic acid, and methanesulfonic acid, p-toluene as the organic acid. Sulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid acid), glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, as Corbic acid, carbonic acid, vanic acid, hydroiodic acid, and the like may be used, and may be preferably hydrochloride. Acid addition salts can be prepared by conventional methods such as dissolving the compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equivalent molar amounts of the compound and acid or alcohol in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered. The non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, iodide, fluoride , Acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suverate, sebacate, Fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitro benzoate, hydroxybenzoate, methoxybenzoate phthalate , Terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylene Sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, beta-hydroxybutyrate, glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, Naphthalene-2-sulfonate, or mandelate.

The cation exchange resin may be used without limitation as long as it does not adversely affect the pharmaceutical activity of clomipramine or a pharmaceutically acceptable salt thereof, and both polyacrylic and polystyrene may be used, for example, meta Cross-linked polymers of methacrylic acid and divinylbenzene (carboxylic acid functional groups and potassium of methacrylic acid form weakly acidic salts) (eg C100HMR ^® , C108DR ^® , C115HMR ^® , C115KMR ^® , IRP64 ^® , IRP88 ^® , INDION204 ^® , INDION214 ^® , INDION234 ^® , INDION234S ^® , INDION264 ^® , INDION414 ^® , INDION464 ^® or INDION294 ^® (Polycryline Potassium)), cross-linked polymers of styrenesulfonic acid and divinylbenzene (sulfonic acid groups and sodium in styrenesulfonic acid form strong acid salts) (eg IRP69 ^® , INDION224 ^® , INDION254 ^® , INDION404 ^® , INDION284 ^® ), or cross-linked polymers of styrene and divinylbenzene (eg AP143 / 1083 ^® , INDION244 ^® ). I am not limited to this.

The 'anionic polymer' may be used without limitation so long as it does not adversely affect the pharmaceutical activity of clomipramine or a pharmaceutically acceptable salt thereof, and includes both natural anionic polymers and synthetic anionic polymers, for example, alginic acid, As polymers having functional groups of carboxylic acid, sulfonic acid, sulfate ester, phosphate ester, phosphonic acid and salts thereof, pectin and derivatives and salts thereof, cellulose (eg carboxymethylcellulose (CMC)) and derivatives and salts thereof, poly Acrylic acid (eg Eudragit ^® ) and its derivatives and salts, galactomannan gums (eg cassia gum, locust bean gum, tara gum, guar gum), carrageenan gum, xanthan gum, tragacand gum, agar, queens Seed gum, starch and derivatives and salts thereof, karaya gum, gum arabic, alginate (eg sodium alginate, propylene glycol eggs) Propyleneglycol alginate) and derivatives thereof and salts thereof, chondroitin sulfate, dextran sulfate, fucoidan, gellan gum, heparin, hyaluronic acid, xylan, polystyrene sulfonate, collagen, polyphosphonic acid, polyphosphate, poly (lactide) and Poly (lactide-co-glycolic acid) and the like, and the like.

In order for the cation exchange resin and the anion polymer to exhibit a synergistic effect as a taste masking component, the weight ratio of the anion polymer to the cation exchange resin is preferably about 1: 0.07-23, about 1: 0.0.07-22, and about 1: 0.07-21. , About 1: 0.07-20, about 1: 0.07-19, about 1: 0.08-23, about 1: 0.0.08-22, about 1: 0.09-21, about 1: 0.1-20, or about 9: 1 -1 may be 19. If the weight ratio is less than about 1: 0.07 or greater than about 1:23, it is difficult to exert a taste masking effect.

The combination of the cation exchange resin and the anionic polymer can effectively mask all the unpleasant tastes of clomipramine in a small amount. The total weight ratio of the cation exchange resin and the anionic polymer as the taste masking component is preferably clomipramine or a pharmaceutical thereof. About 1: 0.5 or more 1: 10 or less, about 1: 0.6 or more 1: 10, about 1: 0.7 or more 1: 10 or less, about 1: 0.8 or more 1: 10 or less, about 1: 0.9 1 or less than 10, about 1: 1 or more, less than 1: 10, about 1: 2 or more, less than 1: 10, about 1: 3 or more, less than 1: 10, about 1: 4 or more, less than 1: 10, about 1: 5 1: less than 10, about 1: 6 or more, less than 1: 10, about 1: 7 or more, less than 1: 10, about 1: 8 or more, less than 1: 10, about 1: 9 or more, and less than 1: 10. If the weight ratio is less than about 1: 0.5, it is difficult to exert a taste masking effect.If the weight ratio is greater than about 1:10, the total weight is increased, which significantly reduces the texture and dosage convenience in the oral cavity. In particular, portability is likely to be offset.

Preferably, the pharmaceutical preparations according to the invention may comprise about 2-150 mg of clomipramine or a pharmaceutically acceptable salt thereof per unit dosage, based on a single unit dose. More specifically, one unit dosage of clomipramine or a pharmaceutically acceptable salt thereof included in the pharmaceutical formulation may vary depending on the specific pharmaceutical use, but the use of clomipramine or a pharmaceutically acceptable salt thereof may vary. A combination of a cation exchange resin and an anionic polymer as a taste masking component within a range of about 2-250 mg of a single dose dose effectively masks the unique taste. Thus, for example, even if it includes all the clomipramine or a pharmaceutically acceptable salt thereof corresponding to the daily dosage in the unit dosage form, it can be taken without a sense of rejection, so that the daily dosage is 1 without having to divide the daily dosage into multiple doses. Can be taken in a single dose, can be taken just before sexual intercourse, can be changed from a continuous treatment to take the drug at regular intervals from the daily treatment to change the treatment method, so if the problem in the continuous treatment every day There is an effect that can eliminate the side effects that are, but the present invention is not limited to these effects.

The pharmaceutical preparations according to the present invention can be used without limitation as long as they are a medicinal use of all diseases, disorders and / or symptoms treated by administering clomipramine or a pharmaceutically acceptable salt thereof as an active ingredient, eg, premature ejaculation, OCD, depressive disorder, panic disorder, metamorphosis disorder, aggression, narcolepsy, dysentery, chronic pain, nocturnal enuresis and / or hair growth walls and the resulting symptoms, but may preferably be used for the treatment of premature ejaculation. .

In the present invention, 'treatment' refers to any action that improves or advantageously changes a disease, a disorder, and the symptoms caused by administration of a pharmaceutical preparation. In addition, the 'treatment' broadly includes the meaning of 'prevention', 'prevention' refers to any action that is suppressed or delayed onset of the disease and the symptoms caused by the administration of the pharmaceutical preparation.

The pharmaceutical preparations according to the invention can be formulated for oral administration, for example tablets, films, suspensions, granules, gels, pills, tinctures. ), Decoction, infusion, spirit, fluid, extract, elixir, extract, syrup, powder, fragrance aromatic water), lemonade (lemonade) and the like can be formulated in various forms. In addition, the tablet may be, for example, orally disintegrating tablets, mucoadhesive tablets, dispersible tablets, sublingual tablets, buccal tablets, chewing tablets Chewable tablets, dispensing tablets, multilayered tablets, press-coated tablets, effervescent tablets, solution tablets, etc. Can be. And those skilled in the art can be used to variously modify the various tablets as needed. More preferably, a formulation that immediately feels the unique taste of clomipramine upon oral administration, such as a liquid form or a disintegrating formulation in the oral cavity (ie, disintegrating in the oral cavity), such as an orally dispersible formulation such as oral dissolution. It may be a formulation such as a film, oral disintegrating tablet, suspension, suspension tablet, fast disintegrating tablet, oral disintegrating granule, oral disintegrating troche, sublingual tablet, powder and / or chewable tablet, and the situation to be portable In addition, in consideration of various purposes such as taste masking (Taste masking), the formulation of the pharmaceutical preparation according to the present invention may be preferred oral dissolution film formulations, fast-acting disintegrating tablet formulation or oral disintegrating granule formulation. The orally dissolving film may be used interchangeably with terms such as film, strip, orally disintegrating film, oral cavity, buccal mucosa, sublingual It refers to the dosage form to paste inside and take. Pharmaceutical formulations for oral administration of oral dispersible film formulations according to the present invention has the advantage that it can be taken without water.

When the pharmaceutical formulation for oral administration according to the present invention is formulated into an oral dissolving film, a polymer must be included for film formation in the present invention. The pharmaceutical preparations for oral administration according to the present invention contain a large amount of ionic components, so compatibility with the polymer is important. Thus, preferably, pullulan, hydroxypropylcellulose (HPC), hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), starch, polyethylene Glycol-polyvinyl alcohol copolymers, copovidone, hydroxyethyl cellulose, hydroxypropyl p-starch, polyvinylcaprolactam-polyvinylacetate-polyethyleneglycol copolymers, poloxamers or mixtures thereof may be used. Can be. The polymer may include 10 to 50% by weight based on the total weight of the dried film, but is not limited thereto.

In preparing a pharmaceutical formulation for oral administration according to the present invention, the pharmaceutical formulation may further include a pharmaceutically acceptable carrier that can be added to the pharmaceutical formulation. The pharmaceutically acceptable carrier includes additives such as excipients, disintegrants, binders, lubricants, emulsifiers, suspending agents, stabilizers and the like commonly used in the pharmaceutical field, and if necessary, sweeteners, flavoring and / or coloring agents, etc. It may be added additionally.

When the pharmaceutical composition of the present invention is used for treating premature ejaculation, other drugs may be used as an active ingredient in addition to clomipramine or a pharmaceutically acceptable salt thereof, as long as the purpose of the present invention is not impaired. For example, serotonin One or more selected from the group consisting of agonists, cetoronin antagonists, adrenergic agonists, adrenergic antagonists, adrenergic nerve blockers, erectile dysfunction agents, PDE 5-inhibitors, erectile agents and combinations thereof. In addition to the drugs described above, a person skilled in the art may further select and use various drugs as necessary.

In another embodiment, the present invention includes a clomipramine or a pharmaceutically acceptable salt thereof as an active ingredient, and includes a cation exchange resin and an anionic polymer together as a taste masking agent. Provided are methods for preparing a formulation.

Preferably, when preparing a pharmaceutical preparation for oral administration comprising adding and stirring a cation exchange resin and an anionic polymer to a liquid clomipramine hydrochloride dissolved, it is possible to take without water and clomipramine hydrochloride as an active ingredient It can provide a method for producing a pharmaceutical formulation for oral administration comprising a.

The present invention includes a step of adding a mixture of a cation exchange resin and an anionic polymer to a clomipramine or a pharmaceutically acceptable salt thereof in a solvent, and having a taste masking effect having excellent taste masking effect. Formulations are possible.

Hereinafter, examples and the like will be described in detail to help understand the present invention. However, embodiments according to the present invention can be modified in many different forms, the scope of the invention should not be construed as limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

Experimental Example 1. Preparation of film formulation containing clomipramine hydrochloride as an active ingredient

Using the components according to Table 2 was prepared a film formulation containing clomipramine hydrochloride as an active ingredient according to the following method, and confirmed the taste masking effect and the film formulation forming ability.

A cation exchange resin and an anionic polymer were added to the liquid clomipramine hydrochloride dissolved and stirred for at least 1 hour. Next, a plasticizer, flavoring agent, coloring agent, sweetening agent, surfactant, and / or diluent is added to the purified water, followed by stirring to dissolve or disperse the same. Homogenizer (Ultra turrax T-25, IKA) was used to homogenize. After adding the polymer (flurane) and homogenizing again using the same homogenizer, the gas in the film preparation was removed under vacuum conditions, and coated on the PET film to have an appropriate thickness. After drying at 60 ~ 80 ℃ to prepare a film formulation containing clomipramine hydrochloride.

The taste masking effect of the film formulation was confirmed by the following method. TM sensory test was carried out with the same weight formulation prepared. The subject placed a sample of the formulation containing the same unit equivalent amount of clomipramine hydrochloride into the mouth, dissolved and spit out for the same time, and simply rinsed the mouth with the same amount of water. After that, the bitter taste and burning time were recorded separately. The interval between tests for each formulation and sample was set to 3 hours or more and the subject was excluded from the next test when the bitter taste or burning effect was maintained for 3 hours or more. In addition, specific evaluation criteria were as follows:

Table 1

1-poor	Retension time of Bitter, burning effects: NLT 60min.
2-not good	Retension time of Bitter, burning effects: NLT 20min.
3-not bad	Retension time of Bitter, burning effects: NMT 20min.
4-excellent	Retension time of Bitter, burning effects: NMT 5min.

In addition, the criteria for evaluating film formulation forming ability were as follows:

Not formed: Difficult to agitate and apply due to the strong viscosity of the film solution.

Bad appearance: Viscosity enough to stir and apply the film solution but uneven and rough appearance of dried film.

Not bad appearance: The stirring and coating of the film solution is good, but the property of the dried film is rough.

Excellent: The stirring and coating of the film solution is very good and the property of the dried film is uniform and flat.

According to the method, there is an excellent effect that effectively prevents API vitrification while simultaneously removing free active pharmaceutical ingredients (APIs) without going through a filtration step, a washing step and / or a drying step. , Taste Masking effect was achieved because cost, effort, etc. were reduced.

TABLE 2

Experimental Example 1-1. Comparison of Effect of Cation Exchange Resin, Anionic Polymer and Clomipramine Hydrochloride Mixing Ratio]

As shown in Table 3, the film preparation was prepared by varying the weight ratio of the cation exchange resin, the anionic polymer and the clomipramine hydrochloride to be mixed, and the taste masking effect and the film formulation forming ability were confirmed.

The film preparation method and the method of confirming taste masking and film formulation formation ability effect were performed as described in Experimental example 1.

TABLE 3

Experimental Example 2. Preparation of fast-acting disintegrating tablet containing clomipramine hydrochloride as an active ingredient

Tablet formulations containing clomipramine hydrochloride as an active ingredient were prepared according to the following method using the components according to Table 4, and the taste masking effect and the film formulation forming ability were confirmed.

A cation exchange resin and an anionic polymer were added to the liquid clomipramine hydrochloride dissolved and stirred for at least 1 hour.

Then, the liquid was filtered and dried to obtain a solid. A binder, a disintegration agent, a diluent, and a lubricant are added to the obtained solid, and then mixed, and a tablet is prepared using a tablet press.

Table 4

Experimental Example 2-1. Comparison of Effect of Cation Exchange Resin, Anionic Polymer and Clomipramine Hydrochloride Mixing Ratio]

As shown in Table 5, the tablets were prepared by varying the weight ratio of the cation exchange resin, the anionic polymer and the clomipramine hydrochloride to be mixed, and the taste masking effect was confirmed.

Tablet manufacturing method and the method of confirming the taste masking effect was carried out as described in Experimental Example 1.

Table 5

Experimental Example 3. Preparation of Granules Containing Clomipramine Hydrochloride as an Active Ingredient

Using the components according to Table 6, according to the following method was prepared a granule formulation containing clomipramine hydrochloride as an active ingredient, and confirmed the taste masking effect and the film formulation forming ability.

A cation exchange resin and an anionic polymer were added to the liquid clomipramine hydrochloride dissolved and stirred for at least 1 hour.

Then, the liquid was filtered and dried to obtain a solid. Separately, a binder, a disintegration agent, and a diluent were added to prepare a liquid, and the obtained solid was placed in a fluidized bed granulator and spray dried to prepare granules.

Table 6

Experimental Example 3-1. Comparison of Effect of Cation Exchange Resin, Anionic Polymer and Clomipramine Hydrochloride Mixing Ratio]

As shown in Table 7, granules were prepared by varying the weight ratios of the cation exchange resin, the anionic polymer, and the clomipramine hydrochloride to be mixed, and the taste masking effect was confirmed.

The granulation method and the method of confirming the taste masking effect were performed as described in Experimental Example 1.

TABLE 7

Claims (12)

1. A pharmaceutical formulation for oral administration comprising clomipramine or a pharmaceutically acceptable salt thereof as an active ingredient and including a cation exchange resin and an anionic polymer as a taste masking agent.
2. The pharmaceutical preparation for oral administration according to claim 1, wherein the active ingredient is clomipramine hydrochloride.
3. The pharmaceutical preparation for oral administration according to claim 1, wherein the cation exchange resin is a polyacrylic cation exchange resin, a polystyrene cation exchange resin, or a mixture thereof.
4. The pharmaceutical preparation for oral administration according to claim 1, wherein the cation exchange resin is a crosslinked polymer of methacrylic acid and divinylbenzene, a crosslinked polymer of styrenesulfonic acid and divinylbenzene, or a mixture thereof.
5. The pharmaceutical preparation for oral administration according to claim 1, wherein the anionic polymer is anionic gum, alginate, polyacrylic acid or a mixture thereof.
6. The pharmaceutical preparation for oral administration according to claim 1, wherein the weight ratio of the anionic polymer to the cation exchange resin is about 1:19-9: 1.
7. The pharmaceutical preparation for oral administration according to claim 1, wherein the total weight ratio of the cation exchange resin and the anionic polymer to the clomipramine or a pharmaceutically acceptable salt thereof is about 1: 0.5 or more and less than 1:10.
8. The pharmaceutical formulation for oral administration according to claim 1, wherein the pharmaceutical formulation for oral administration is for treating premature ejaculation.
9. The pharmaceutical formulation for oral administration according to claim 1, wherein the pharmaceutical formulation for oral administration is formulated into a formulation that is dissolved or dispersed in the oral cavity.
10. The pharmaceutical formulation for oral administration according to claim 9, wherein the formulation is an oral soluble film, fast disintegrating tablet or oral disintegrating granule.
11. A method of preparing a pharmaceutical formulation for oral administration comprising clomipramine or a pharmaceutically acceptable salt thereof as an active ingredient, and including a cation exchange resin and an anionic polymer as a taste masking agent.
12. A method for preparing a pharmaceutical preparation for oral administration comprising clomipramine hydrochloride as an active ingredient, comprising adding and stirring a cation exchange resin and an anionic polymer to a liquid clomipramine hydrochloride lysate.