MXPA01004991A - Dispersible phospholipid stabilized microparticles - Google Patents

Abstract

Rapidly dispersing solid dry therapeutic dosage form comprised of a water insoluble compound existing as a nanometer or micrometer particulate solid which is surface stabilized by the presence of at least one phospholipid, the particulate solid being dispersed throughout a bulking matrix. When the dosage form is introduced into an aqueous environment the bulking matrix is substantially completely dissolved within less than 2 minutes thereby releasing the water insoluble particulate solid in an unaggregated and/or unagglomerated state. The matrix is composed of a water insoluble substance or therapeutically useful water insoluble or poorly water soluble compound, a phospholipid and optionally also at least one non-ionic, anionic, cationic or amphipathic surfactant, together with a matrix or bulking agent and if needed a release agent. The volume weighted mean particle size of the water insoluble particle is 5 micrometers or less.

Description

or i X DISPERSAB MICROPARTICLES ARE STABILIZED WITH PHOSPHOLIPID FIELD OF THE INVENTION 5 This invention relates to compositions comprising particles of water insoluble or poorly soluble drugs of a size of about 0.05 to 10 microns having a substance or combination of substances that modify the surface, which at least is a phospholipid, adsorbed on the surface thereof. The • composition includes one or more matrix forming substances which are present in an amount sufficient to allow freeze drying and subsequent release of the drug particles coating the surface upon contact with a watery environment. The small particles coated on the surface are sometimes referred to as microcrystals (U.S. Patent Nos. 5,091,187 and 5,091,188), microparticles (WO 98/07414), nanoparticles (U.S. Pat. 5,145,684 and 5,302,401). This invention further provides methods for making dry compositions of insoluble or poorly water soluble drug particles having substances or combinations of surface modifying substances, which at least one is a phospholipid, adsorbed on the surface of the same and substances that form matrices. The substance or substances forming matrices are present in an amount sufficient to allow drying by • freezing, such as by lyophilization, with the subsequent release of drug particles coated on the surface after contact with an aqueous environment. The method comprises contacting the phospholipid-coated particle with the matrix-forming substance (s) for a time and under conditions sufficient to allow the phospholipid-coated drug particles to dry by freezing. BACKGROUND OF THE INVENTION The poor bioavailability of water insoluble compounds has long been a problem in the pharmaceutical and diagnostic industry. Although compounds with a solubility in water greater than 1 percent weight / volume are not expected to present problems of bioavailability and absorption related to dissolution, many new chemical entities exhibit aqueous solubility much lower than this value (see Pharmaceutical Dosage Forms - 20 Tablets, Vol 1, page 13, Edited by H. Liberman, Marcel Dekker, Inc, 1980). Many extremely useful compounds are set aside in their development or otherwise formulated otherwise undesirable due to their poor solubility in water. A large number of these compounds are unstable in medium watery and some require dissolution in oil, returning the dose form frequently unpleasant to take and painful to be used via the parenteral route of administration. This can lead to poor patient cooperation and potentially a much greater overall expense in treatment due to unnecessary hospitalizations. It is therefore desirable to develop a formulation of these water-insoluble compounds that can be dosed in the simplest manner possible: a solid dosage form that disperses rapidly. There are many methods for preparing solid dosage drugs that disperse rapidly. Traditional approaches to this problem have included the dispersion of an active biological ingredient with pharmaceutically acceptable excipients using blending techniques and / or granulation techniques. Specific functional excipients known in the art can be used to help release the drug, such as effervescent disintegrating substances as shown in U.S. Patent No. 5,178,878. As a method of improving the disintegration of the solid dosage form, thereby releasing the medicament, freeze drying techniques employed as described in US Pat. Nos. 4,371,516; 4,758,598; 5,272,137. Additionally, drying techniques have been used by spray for similar purposes as for example U.S. Patent No. 5,776,491 which discloses the use of a polymeric component, a solubilizing component and a bulking agent as a matrix-forming composition after spray drying. This particulate matrix quickly disintegrates after introduction in an aqueous environment to release the drug. Although these approaches produce solid dosage forms of rapid drug release, they suffer from several disadvantages particularly with drugs that are insoluble in water or poorly soluble in water. In these cases, suspensions of water-insoluble compounds are likely to settle before completing the freeze-drying or spray-drying process leading to the aggregation of particles and potentially non-homogeneous dry dosage forms. Additionally, large macromolecules of polysaccharides, typified by dextrans, when used as matrix formers have been implicated in agglomeration tendencies in reconstituted dry suspensions of liposomes (Miyajima, 1997). Therefore, the proper selection and use of saccharide matrix formers remains difficult to achieve, we believe that it is linked to the physicochemical nature of the surface of the water-insoluble particle under consideration. Additionally, the suspensions of compounds insoluble in water would undergo unwanted particle size growth as a result of the Ostwald maturation process. In order to shorten this process, stabilization of these micronized materials suspended in an aqueous environment can be achieved using compositions of a variety of pharmaceutically acceptable excipients known to those skilled in the art. These approaches can be found as an example, in commonly assigned U.S. Patent Nos. 5,631,023 and 5,302,401 and European Patent EP0193208. For example, U.S. Patent No. 5,631,023 describes a method for preparing tablets that dissolve rapidly (10 seconds) using xanthan gum at a maximum of 0.05 weight percent as the suspending and flocculating substance with gelatin in the which particles of the water-insoluble drug are dispersed. Mannitol is used as the preferred cryoprotectant. The suspension is dried by freezing in molds to generate the solid dosage form. In US Pat. No. 5,302,401 a method for reducing the particle size which increases during lyophilization is described. Describes a composition that contains particles that have a surface modifier adsorbed on the surface together With a cryoprotectant, the cryoprotectant is present in an amount sufficient to form a nanoparticle-cryoprotectant composition. A preferred surface modifier is polyvinylpyrrolidone, a preferred cryoprotectant is a carbohydrate such as sucrose. Methods for making particles having a surface modifier adsorbed on the surface and a cryoprotectant associated therewith are also described. The patent specifically refers to 5 percent danazol with 1.5 percent PVP and sucrose (2 percent) or mannitol (2 percent) as the cryoprotectant. Thus, although several cryoprotectants are available and function adequately to protect the active substance during lyophilization, the resulting solid product is often difficult to redisperse in an aqueous medium. European Patent EP 0193208 describes a method of lyophilizing latex particles coated by reagent to allow reconstitution without aggregation and discusses the need to incorporate a zwitterionic regulator such as an amino acid, a stabilizer such as PVP or bovine albumin and a cryoprotectant such as Dextran. UNCLE or another polysaccharide. SUMMARY OF THE INVENTION This invention is directed to an improvement in the dispersibility of micronized particles through the specific selection of excipients and of the methodology necessary to coat the primary particles. Inherent in this approach is the ability to produce stable aqueous suspensions of micron-sized particles or submicras of water-insoluble or poorly water-soluble compounds. These particles, which are required in the practice of the present invention, can be prepared according to the methods described in U.S. Patent Nos. 5,091,187 and 5,091,188 as well as in International Publication WO 98/07414, the description of which is incorporated herein by reference. Briefly, the water insoluble or poorly soluble compounds are dispersed in an aqueous medium in the presence of substances or combinations of surface modifying substances of which at least one is a phospholipid adsorbed on the surface thereof. Particulate fragmentation occurs when the aforementioned suspension is subjected to stresses as a result of a process with the use of various methods known in the art and includes, but is not limited to, sonification, milling, homogenization, microfluidization, and anti-solvent precipitation. and solvent. The particle thus produced is known as a microparticle which is defined herein as a solid particle of irregular, non-spherical or spherical shape having a nominal diameter of from nanometers to microns on which at least one substance modifying the polymer is adsorbed. surface between which a It is a phospholipid. According to this invention the microparticle suspension thus produced is further mixed with surface modifying substances and / or matrix forming substances which are present in an amount sufficient to allow freeze drying and subsequent release of the drug particles. Coated on the surface after contact with an aqueous environment. The selection of these compounds serves to minimize the tendency of the microparticles to aggregate after drying. These aggregates are extremely difficult to redisperse due to the very large surface area of the particle that facilitates the degree of contact available for the particles to interact resulting in irreversible crosslinks. Small particle sizes of drugs are often needed in drug formulation in order to maximize surface area, bioavailability, and dissolution requirements. The introduction of a suitable substance to form matrix in the process noted above serves to stabilize the phospholipid-coated drug particle during the freeze-drying process and in the freeze-dried product resulting from suppressing any tendency of particle agglomeration or growth of the particles.

DESCRIPTION OF THE INVENTION The present invention provides a solid dosage form of rapid disintegration of water-insoluble compounds, which mainly releases particles stabilized with one or more surface modifiers, including but not limited to phospholipids. Examples of some preferred water insoluble drugs include antifungal substances, immunosuppressive and immunoactive substances, antiviral substances, antineoplastic substances, analgesic and anti-inflammatory substances, antibiotics, antiepileptics, anesthetics, hypnotics, sedatives, antipsychotic substances, heurolépticas substances, antidepressants, anxiolytics , anticonvulsant substances, antagonists, blocking substances of neurons, anticholinergic and cholinomimetic substances, antimuscarinic and muscarinic substances, antiadrenergic and antarrhythmic substances, antihypertensive substances, hormones and nutrients. A detailed description of these drugs can be found in Remington's Pharmaceutical Scienses, 18th Edition, 1990, Mack Publishing Co., PA. The concentration of the water-insoluble ingredient in the aqueous suspension can vary between 0.1 weight / weight percent and 60 weight / weight weight, preferably between 5 weight / weight and 30 weight / weight percent. The water-insoluble compound is first prepared as an aqueous suspension in the presence of one or more substances Surface stabilizers, of which at least one is a phospholipid. The phospholipid can be any natural or synthetic phospholipid, including but not limited to, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinolistol, phosphatidiglycerol, phosphatidic acid, lysophospholipids, egg or soybean phospholipid or a combination thereof. The phospholipid can be salted or desalted, hydrogenated or partially hydrogenated or natural, semi-synthetic or synthetic. The concentration of the phospholipid ingredient in the aqueous suspension can vary between 0.1 weight / weight percent and 90 weight / weight weight, preferably between 0.5 weight / weight and 50 weight / weight weight and more preferably between 1 weight / weight. weight and 20 percent weight / weight. Examples of some second and additional convenient surface modifiers include: (a) natural surfactants such as casein, gelatin, natural phospholipids, tragacanth, waxes, enteric resins, paraffin, acacia, gelatin, and cholesterol, (b) nonionic surfactants such as ethers of polyoxyethylene fatty alcohols, sorbitan fatty acid esters, polyoxyethylene fatty acid esters, sorbitan esters, glycerol monostearate, polyethylene glycols, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, poloxamers, polaxamines, methylcellulose, hydroxycellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, non-crystalline cellulose, and synthetic phospholipids (c) anionic surfactants such as potassium laurate, triethanolamine stearate, sodium lauryl sulfate, alkyl polyoxyethylene sulphates, sodium alginate, dioctyl sodium sulfosuccinate, negatively charged phospholipids ( phosphatidyl glycerol, phosphatidyl inositol, phosphatidylserine, phosphatidic acid and its salts), and negatively charged glyceryl esters, sodium carboxymethylcellulose, and calcium carboxymethylcellulose, (d) cationic surfactants such as quaternary ammonium compounds, benzalkonium chloride, cetyltrimethylammonium bromide , and lauryl dimethylbenzylammonium chloride, (e) colloidal clays such as bentonite and veegum. A detailed description of these surfactants can be found in Remington's Pharmaceutical Scienses, 18th Edition, 1990, Mack Publishing Co., PA; and Theory and Practice of Industrial Pharmacy, Lachman et al., 1986. The concentration of additional surfactants in the aqueous suspension can vary between 0.1 weight / weight percent and 90 weight / weight weight, preferably between 0.5 weight / weight and 50 weight percent. percent weight / weight and more preferably between 1 weight / weight percent and 20 weight / weight percent. These surfactants can be added initially during the composition or added after processing before freeze drying or a combination of both depending on the nature, concentration and number of the surfactants. The resulting coarse dispersion is primarily intended to distribute the surfactants throughout the aqueous medium using traditional mixing methods involving cutting, extrusion, agitation and / or cavitation. The coarse dispersion is known as premix for the purposes of this description. The premix is subjected to a process that facilitates the fragmentation of particles including but not limited to sonification, grinding, homogenization, microfluidization, and anti-solvent precipitation and solvent. The friction time can vary and depends on the physicochemical characteristics of the medication, the physicochemical characteristics of the surfactant and the selected friction process. As an example, high pressure homogenization processes can be employed as typified by the use of equipment such as APV Gaulin E15, Avestin C50 or MFIC Microfluidizer M110EH. In this process, the particles in the premix are reduced in size at a pressure and temperature that do not significantly compromise the stability of the drug and / or the surfactants. The processing pressures of about 140 kilograms / cm2 to 2100 kilograms / cm2, preferably from about 350 kilograms / cm2 to 1400 kilograms / cm2, more preferably from about 700 kg / cm2 at 1260 kilograms / cm2 and operating temperatures of about 2 ° C to 65 ° C, more preferably 10 ° C to 45 ° C are convenient. The processing fluid is cycled through the homogenization chamber to ensure that the entire mixture of the fluid is subjected to discrete homogenization to result in a homogeneous suspension of micron or submicron particles. The weighted average volume of particle size of the resulting suspended therapeutic substance is measured to be between 0.05 microns to 10 microns, preferably between 0.2 microns to 5 microns using the instrument based on laser light diffraction, Malvern Mastersizer Microplus. The resulting homogenous suspension of microparticles stabilized by one or more surface modifiers is then mixed with volume forming and / or releasing substances to form a matrix (dry or as an aqueous solution) and then dried. The matrix-forming or volume-forming substance provides a mass in which the drug particles are embedded or retained. The release substance helps the disintegration of the matrix when it makes contact with aqueous medium. The volume / release forming substances are chosen in order to produce a support matrix which, after drying, will provide rapidly dispersible tablets which release the primary particles after reconstitution in an aqueous medium. Examples of matrix / release forming substances include (a) saccharides and polysaccharides such as mannitol, trehalose, lactose, sucrose, sorbitol, maltose; (b) humectants such as glycerol, propylene glycol, polyethylene glycol; (c) natural or synthetic polymers such as gelatin, dextran, starches, polyvinylpyrrolidone, poloxamers, acrylates; (d) inorganic additives such as colloidal silicon dioxide, tribasic calcium phosphate and; (e) cellulose-based polymers such as microcrystalline cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, methyl celluloses. Matrix forming substances can be added before producing the micronized particles of the therapeutic substance (formulation) or the homogeneous microparticle suspension before freeze drying. The concentration of the matrix forming substances in the aqueous suspension can vary between 0.1 weight / weight percent and 90 weight / weight weight, preferably between 0.5 weight / weight and 50 weight / weight weight and more preferably between 1 weight 100 weight / weight and 20 weight / weight percent. The prepared aqueous suspension can be dried using various methods known in the art. Spray drying, spray coating and freeze drying are among the most common methods. The examples cited in Table 1 also use freeze drying as the drying method but this is not intended to be limiting in any way.

The preferred method of freeze drying is by lyophilization including sublimation of the frozen water of the aqueous suspension medium under reduced pressure. The lyophilization of this suspension can be carried out in 5 convenient containers such as glass jars, open trays, molds of unit solution forms or on-site spraying on a support matrix. By way of example of the lyophilization process, the prepared microparticle suspension containing matrix forming substances is distributed in stainless steel trays that are placed on pre-balanced shelves maintained at a temperature of 5 ° C inside a sealed chamber, with nominal pressure. The prepared suspension is then subjected to a decreasing temperature at a rate of 5 ° C / minute to -50 ° C until all the suspension medium is completely solidified. This procedure uses only moderate temperature gradient due to energy losses between different limits ^ fc (shelf-tray-liquid). As a general rule, the typical time to freeze a layer of one centimeter of a The diluted aqueous suspension is 40-90 minutes at a temperature of -50 ° C. Freezing out of the lyophilization chamber can also be carried out by: (a) freezing on cooled plates, eg, in trays or in the form of small particles on a drum cooler, (b) dripping on nitrogen liquid or in some other liquid cooler, (c) co-sprinkle with C02 liquid or liquid nitrogen, or (d) freeze with cold air circulation. The separate cooling is necessary for the realization of continuous freeze drying. The equipment for producing small granules by dripping the solution in liquid nitrogen is commercially available as the Cryopel® process (Buchmuller and Weyermanns, 1990). Direct freezing inside the lyophilization chamber is advantageous if the product requires handling under aseptic conditions such as the situation in the preparation of injectable dry formulations. The solidified prepared suspension thus obtained is maintained at this temperature for a period of 2 hours to ensure that all crystallization is complete. The pressure inside the chamber is reduced to a pressure of approximately millimeters of mercury and preferably up to about 0.1 millimeter of mercury. Sublimation of the frozen water is carried out by raising the temperature of the lyophilizer shelf to approximately -30 ° C to -10 ° C and keeping the material at this temperature for approximately 20 hours until the primary drying step is completed. The drying time depends on several factors, some of them quite constant and can be approximated as the heat of sublimation of the ice, thermal conductivity of the frozen suspension and, the mass transfer coefficient. Other factors such as temperature or pressure in the chamber can vary considerably. The temperature of the shelves can be increased further to effect a secondary drying which is considered necessary according to the composition of the sample. The material is collected from the lyophilization cycle after returning the chamber to ambient conditions. The collected dry material can be passed through a coarse grinding operation to facilitate handling or other mixing operations with other excipients necessary to complete the required solid dosage form. These may include tamping aids for compression, glidants for the encapsulation of hard gelatin or dispersants for dry powder inhalers. The matrix forming substance used in the present invention must be dissolved or dispersed after contact with an aqueous environment and release the therapeutic substance particle coated with phospholipid. After reconstitution, the product reverts to a suspension having the same degree of dispersion as the previously dry suspension, preferably not more than 20 percent by weight and preferably not more than 10 percent by weight and ideally less than 1 percent by weight. weight percent of primary particles added as revealed by the particle size and methods microscopic ones known in the art. Surprisingly, the freeze dried suspension prepared according to the present invention can be stored for long periods of time, even at high temperature and humidity, without loss of its redispersibility characteristics after reconstitution and thus is essentially devoid of aggregation of particles. The freeze dried suspension prepared according to the composition of Examples 6-10 herein can be stored for at least 60 days at room temperature indicating the possibility of long-term storage consistent with shelf life of the form of pharmaceutical dosage. The solid dosage material prepared according to the present invention is defined as possessing the characteristics of being rapidly dispersible. This characteristic is identified as the time required for the complete disintegration of the dry cake by freezing that arises from this invention when it is subjected to an aqueous medium as occurs after the administration of a dosage form to live systems. The disintegration time can be measured by carrying out in vi tro tests such as observing the disintegration time in water at 37 ° C. The dose material is immersed in water without forcible agitation after which the time required for the material to substantially disperse is observed. In the context of definition of "fast", the disintegration time is expected to be less than 2 minutes and preferably less than 30 seconds and more preferably less than 10 seconds. The rate of dissolution or release of the active ingredient can also be affected by the nature of the medicament and the microparticle composition so that it can be rapid (5-60 seconds) or intermediate (in the order of 75 percent disintegration in 15 minutes) or sustained release. In some cases, visual microscopic observation or micrographs of electron scanning may reveal the presence of aggregates of particles however, these particles are small in size and consist of aggregates of the previously frozen original dry suspension particles. These aggregates are easily dispersed by low energy levels such as short periods of sonification or physical agitation and as such present the key feature of this invention namely the prevention of particle size growth and irreversible aggregation and / or agglomeration. EXAMPLES The present invention of a solid drug, which is rapidly dispersed, is illustrated by way of the examples summarized in Table 1. The compositions noted in this table are expressed on a weight percent basis of the dry product It is understood that the substance by volume can be added to the suspension before the homogenization step or before the drying step. • twenty-one Symbols and Note: CyA = Ciclosporin; E80 = LipoidE80; FEN = Fenofíbrato; ITR = Itraconazole; MAN = Mannitol; NaDeox = sodium deoxycholate; P100H = Phospholipon 100H; PVP17 = Polyvinyl pyrrolidone; SOR = Sorbitol; SUC = Sucrose; TRE = Trehalose Formulations 1 and 2 as shown in the above table illustrate that the reconstitutable particles are obtained from these compositions, indicating that the relatively large size of the particles (approximately 10 microns) has a small problem from an aggregation perspective. These relatively large particles are easily achieved by traditional particle fracturing techniques. However, in order to appreciably affect bioavailability, particles that are an order of magnitude in size are required. These particles are obtained using methods described in U.S. Patent Nos. 5,091,187 and 5,091,188 as microcrystals, International Patent WO 98/07414 as microparticles, and U.S. Patent Nos. 5,145,684 and 5,302,401 as nanocrystals. It is the particles arising from these compositions that require a specific excipient selection and specific processing conditions in order to recover the original suspended particle. Examples 3 to 5 illustrate that certain microparticle compositions are not favorably reconstituted when using traditional freeze-dried cryoprotectants such as lactose or PVP17 as described in U.S. Patent No. 5,302,401. For these examples, large aggregates composed of primary particles are formed adherents Examples 6 to 10 illustrate that the original suspension particle recovers easily and quickly after reconstitution of the dry powder without requiring excessive agitation. These examples require careful selection of the bulking agent which can also act as a cryoprotectant as well as a humectant, such as trehalose in formulation 8 and mannitol in formulation 10. Alternatively, when a single bulking substance forming matrix does not it is convenient, as in the case of sucrose, the composition may include a mixture of volume forming substances selected from pharmaceutically acceptable substances such as sucrose, trehalose, mannitol, sorbitol, or lactose. The formulations of Examples 6, 7, and 9 demonstrate this type of composition. The volume-weighted particle size distribution profiles of fenofibrate formulation 6 are shown in examples 6 and 7, respectively, before and after the lyophilization / reconstitution step. This example demonstrates the same scenario of no change in the profile of particle size distribution after lyophilization and reconstitution. Without intending to propose any particular theoretical explanation, it can be speculated that the compounds of the volume-forming substance mixture can serve simultaneously to inhibit the increase in particle size in lyophilization / reconstitution by one or more mechanisms including cryoprotection, wetting action, dispersibility, and others. These criteria are surprisingly important considerations when attempting to recover the non-aggregated particulate suspension after reconstitution of a dry dosage form comprising a phospholipid as one of the surface stabilizers. In addition to the exemplary compositions mentioned above, the formulations of this invention may additionally contain suitable amounts of pH regulating salts and pH adjusting substances such as sodium hydroxide and / or pharmaceutically acceptable acids. Experts in the chemistry of phospholipids know that a pH less than 4 and greater than 10 phospholipid molecules undergo extensive hydrolysis. Therefore, the pH of the suspension is usually adjusted in this range before homogenization. If necessary, the pH can be readjusted before the drying step. Although the invention and the examples have been described in connection with what is currently considered to be the most practical and preferred embodiment, it will be understood that the invention is not limited to the embodiments described, but on the contrary, is intended to cover various modifications and arrangements. equivalents included within the spirit and scope of the following claims.

Claims (10)

1. A rapidly dispersing solid therapeutic dosage form comprising a water insoluble compound that exists as a solid in nanometric and micrometer particles, which is surface stabilized with one or more surface modifiers of which at least one may be a phospholipid , the particulate solid dispersing through the volume-forming matrix optionally also includes a releasing substance which constitutes a dry therapeutic dosage form which when the dosage form is introduced in an aqueous environment the volume-forming / release matrix is it substantially completely disintegrates in less than 2 minutes whereby the water-insoluble particulate solid is released in a non-aggregated and / or non-agglomerated state.

2. The solid dosage form which is rapidly dispersed according to claim 1, characterized in that the water-insoluble particulate solid component consisting essentially of a composition of a water-insoluble substance comprising particles of an insoluble useful compound in water or poorly soluble in water, a phospholipid and optionally also at least one nonionic, anionic, cationic or amphipathic surfactant, wherein an average volume particle size Weighted particle insoluble in water is 5 microns or less.

3. The solid dosage form that is rapidly dispersed according to claim 1, characterized in that the volume / release matrix component is selected from saccharides, polysaccharides, humectants, natural or synthetic polymers, inorganic additives or polymers based on in cellulose.

4. The solid dosage form that is rapidly dispersed according to claim 3, characterized in that the polyol, saccharide or polysaccharide is mannitol, trehalose, lactose, sucrose, sorbitol, dextrose, mulodextrose or maltose.

5. The solid dosage form that is rapidly dispersed according to claim 3, characterized in that the humectant is glycerol, propylene glycol or polyethylene glycol.

6. The solid dosage form that is rapidly dispersed according to claim 3, characterized in that the natural or synthetic polymer is gelatin, dextran, starches, polyvinylpyrrolidone, a poloxamer or an acrylate.

7. The solid dosage form that is rapidly dispersed in accordance with claim 3, characterized in that the inorganic additive is a colloidal silicon dioxide or tribasic calcium phosphate.

8. The solid dosage form which is rapidly dispersed according to claim 3, characterized in that the cellulose-based polymer is microcrystalline cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose or methyl cellulose.

9. The solid dosage form that is rapidly dispersed according to claim 1, characterized in that the disintegration time in an aqueous medium is less than 2 minutes and preferably less than 60 seconds, more preferably less than 30 seconds, and more preferably less than 10 seconds.

10. The solid dosage form that is rapidly dispersed according to claim 1, characterized in that it also contains an effervescent substance, a binder, a taste, a polymer coating on the external surface of the dosage form, a color or combinations thereof.