AU2013263795B2 - A fast dissolving pharmaceutical composition - Google Patents

Abstract

H:\rec\Intenvoven\NRPo1' \DCC\REC\ii5 27 DOC-2/I/2013 The subject invention is directed to a pharmaceutical composition comprising an open matrix network carrying a pharnaceutically active ingredient, wherein the open matrix network comprises levan.

Description

H:rcnevv RP \DCC\REC\58527DOC-7 / A FAST DISSOLVING PHARMACE UTTICAL COMPOSITION This application is a divisional of Australian Patent Application No. 2011234637, the entire content of which is incorporated herein by reference. FIELD OF THE INVENTION The subject invention relates to fast dissolving pharmaceutical compositions, to methods of making them and to their use in the treatment and prophylaxis of diseases in mammals, particularly humans. BACKGROUND OF THE INVENTION Fast dissolving pharmaceutical dosage forms which are designed to release an active ingredient in the oral cavity are well known and can be used to deliver a wide range of drugs (Critical Reviews in Therapeutic Drug Carrier Systems, 21(6),:433-475 (2004); Seager H. (1998), J Phar, Pharmacol 50:375-382; Bandiri et al. (January 2008), Asian Journal of Pharmaceutics 2-11). In a fast dissolving dosage form, a drug may physically be trapped in a matrix composed of e.g. mannitol and fish gelatin (EP 1501534; EP1165053), modified starch (US6509040), pullulan in combination with an amino acid (EP 1803446), or maltodextrin in combination with sorbitol (US2004 0228919). The solution, suspension or dispersion of the drug and the carrier material may be filled into blister cavities, frozen and thereafter lyophilized. However, dosage forms produced in this manner are mostly fragile and brittle, have limited physical strength, and cannot withstand any pressure. In addition, dosage units so produced are difficult to pack and unpack. SUMMARY OF TI- INVENTION The subject invention provides new fast dissolving oral pharmaceutical compositions typically in a unit dosage form, typically oral lyophilisates (also named orally disintegrating tablets). Fast dissolving dosage forms of the invention have relatively high tensile strength (i.e. force required to break a tablet in a three-point bending test) on the - 1 - H:\rec\Interwoven\NRPortbl\DCC\REC\8327007 Ldocx-1/09/2015 one hand and a fast disintegration/dissolution time on the other hand. This relatively high tensile strength permits, amongst others, to easily remove the composition from its container, typically a blister pack, without disintegration. The unit dosage form of the invention can typically be handled in a manner similar to that of a conventional compressed tablet, with disintegration occurring only upon contact with an aqueous liquid or with saliva within the mouth. In one aspect, the present invention provides a pharmaceutical composition comprising: (a) at least one matrix-forming agent that is levan to form an open matrix network; and (b) at least one pharmaceutically active ingredient chosen from desmopressin and desmopressin acetate, carried by the open matrix network, wherein at least 80% of the composition dissolves within 30 seconds upon contact with an aqueous solution or with saliva, and the composition is an orodispersible pharmaceutical dosage form. In another aspect, the present invention provides a pharmaceutical composition prepared by a process comprising at least a step of sublimating a solvent from a liquid preparation that comprises: (a) at least one matrix forming agent that is levan; and (b) at least one pharmaceutically active ingredient chosen from desmopressin and desmopressin acetate, wherein at least 80% of the composition dissolves within 30 seconds upon contact with an aqueous solution or with saliva, and the composition is an orodispersible pharmaceutical dosage form. In another aspect, the present invention provides a pharmaceutical composition comprising: (a) at least one matrix-forming agent that is levan to form an open matrix network; and (b) desmopressin carried by the open matrix network, wherein at least 80% of the composition dissolves within 30 seconds upon contact with an aqueous solution or with saliva, and the composition is an orodispersible pharmaceutical dosage form. - 1A- H:\rec\Interwoven\NRPortbl\DCC\REC\8327007 Ldocx-1/09/2015 In another aspect, the present invention provides a blister pack having one or more depressions disposed therein, wherein each of the one or more depressions comprises a pharmaceutical composition, the composition comprising: (a) at least one matrix-forming agent that is levan to form an open matrix network; and (b) at least one pharmaceutically active ingredient chosen from desmopressin and desmopressin acetate carried by the open matrix network, wherein at least 80% of the tablet dissolves within 30 seconds upon contact with an aqueous solution or with saliva, and the composition is an orodispersible pharmaceutical dosage form. In one embodiment, the present invention provides a pharmaceutical composition comprising an open matrix network carrying a pharmaceutically active ingredient, wherein the open matrix network is comprised of levan. In another embodiment, the present invention provides a pharmaceutical composition comprising a matrix carrying a pharmaceutically active ingredient, the matrix rapidly disintegrating upon contact with an aqueous solution or with saliva, said matrix comprising levan. The pharmaceutical composition of the invention is unique in that it has a relatively high tensile strength, on the one hand, and a rapid dissolution in an aqueous medium or in saliva, on the other hand. The relatively high tensile strength permits the handling of the composition in a manner similar to that of a regular compressed tablet including, in particular, removal from a package in which they are held, e.g. a blister pack, without risk of damaging the dosage form between the fingers. Notwithstanding this tensile strength, the composition of the invention disintegrates rapidly when contacted with an aqueous medium or with saliva, in particular the composition rapidly disintegrates when taken orally. The disintegration in an aqueous medium or in the oral cavity upon consumption (where it disintegrates upon contact with saliva) is typically within less than 30 seconds, and more typically within less than 10 seconds, at times less than 9, 8, 7, 6, 5, 4, 3, 2 or even 1 second. - 1B - H:\rec\Interwoven\NRPortbl\DCC\REC\8327007 Ldocx-1/09/2015 Accordingly, the invention further provides a pharmaceutical composition comprising a pharmaceutically active ingredient, having a tensile strength so as to allow consumer handling of the composition (typically in a unit dosage form) in a manner similar to that of a compressed tablet, the pharmaceutical composition of the invention typically having a tensile strength ranging between about 0.05 to 1.6 N/mm 2 and a rapid dissolution rate such that at least 80% of the composition is disintegrated in an -2aqueous medium or in saliva in less that 30 seconds, at times less than 10 seconds and even less than 9, 8, 7, 6, 5, 4, 3, 2. or . second. The pharmaceutical composition of the invention may be obtained by subliming a solvent (e.g. water), for example in a freeze drying process, from a liquid preparation that comprises the active ingredient and the matrix forming agents) in solution. According to one embodiment, unit dosage quantities of the liquid preparation are introduced into depressions and sublimation is then carried out thereby obtaining (after sublimation) a pharmaceutical composition in a unit dosage form. The depressions may be those of an open blister pack and following the sublimation step, and thereby the formation of the solid unit dosage form of the composition in the depression, a sealing film or foil is placed over the depressions to form a sealed blister pack. The invention further provides a process for preparing a pharmaceutical composition that comprises subliming a solvent from a liquid preparation comprising a pharmaceutically active ingredient and levan in the solvent. The invention also provides a process for the preparation of a pharmaceutical composition comprising (a) preparing a solution comprising levan and an active ingredient in a solvent; (b) freezing said solution; (c) subliming the solvent from the frozen solution, wherein the pharmaceutical composition so obtained is in fast dispersing dosage form which disintegrates within less than 30 seconds upon contact with an aqueous solution or with saliva. DElTAILED DESCRIPTION OF THE INVENTION The subject invention provides a fast-dissolving, typically orodispersible, phannaceutical composition, usually prepared and provided in unit dosage forn, typically an oral lyophilisate, comprising an active ingredient and one or more excipients. At least one of the excipients, normally the main matrix forming agent, is the polysaceharfde levan. The following are some of the terms used above and below in this patent specification and claims: The terms "active ingredient" or "pharmaceutically active ingredient" will be used interchangeably herein. The term "pharraceutical composition" and "composition" are interchangeably used herein to refer to a pharmaceutical composition of the invention. The term "unit dosage form" or "dosage form" will be used herein to refer to said composition which is formulated with an amount of an active pharmaceutical ingredient (API) in a dose for administration as a single dose to a target individual. The unit dosage form may be adapted, depending on the nature of the active ingredient, the indication, the disease stage and various other factors known per se for once, twice, thrice or any other number of daily administrations. The term "carrying" should be understood to encompass any forn of interaction between an active ingredient and the matrix that allows the matrix to hold and/or contain an amount of active ingredient and release it to the aqueous medium or to saliva upon disintegration of the matrix. The term "matrix" should be understood to denote a solid carrier medium for an active ingredient. The matrix comprises one or more excipients. The excipients that form the matrix may be referred to herein, at times, as "matrix forming agents" and each of said agents as "matrixjbrinng agent". The term "an open matrix network" should be understood to encompass a matrix of water-soluble or water-dispersible carrier material (matrix-forming agentss) having interstices dispersed throughout. The matrix rapidly disintegrates upon contact with an aqueous solution or with saliva. In one embodiment, levan is the sole matrix forming agent in the composition. In another embodiment, one or more secondary matrix forming agents may be present in the composition. 4 Non-limiting examples of sugars, sugar alcohols, monosaccharides, disaccharides, trisaccharides, polysaccharides, proteins, amino acids, gums and the like, which are useful as secondary matrix forming agents, include without limitation, mannitol, trehalose. raffinose, inositol, pullulan, sucrose, lactose, dextrose. erythritol, xylito, lactitol, maltitol, isomalt, alanine, arginine, threonine, glycine, cysteine, serine. histidine, valine, praline, lysine, asparagine, glutamine, ribose, glucose, galactose, fructose, maltose, naltotriose, guargum, xanthan gum, tragacanth gum, veegum and so forth. Generally, the balance of the formulation can be matrix. Thus the percentage of the levan matrix can approach 100%. The amount of the secondary matrix forming agent useful in accordance with the present invention may range from about 0 to about 90%. In one embodiment of the invention, levan is the main matrix forming agent in the composition. In another embodiment, the composition further comprises mannitol or raffinose or trehalose or combinations thereof as secondary matrix forming agent. In one embodiment, levan is the matrix forming agent, comprising 10 - 99.99% out of the entire weight of the composition. In another embodiment, levan comprises 30 75% out of the entire weight of the composition. In yet another embodiment, levan comprises 40-70% out of the entire weight of the composition. In yet another embodiment, levan comprises 50-65% out of the entire weight of the composition. In other embodiments, mannitol or trehalose or raftinose or combinations thereof are used as secondary matrix forming agents, comprising 0 - 89.99% out of the entire weight of the composition. In one embodiment, these secondary matrix forming agents comprise 15-50% out of the entire weight of the composition. In another embodiment, these secondary matrix forming agents comprise 25-50% out of the entire weight of the compostion. Thus, a composition of the invention can be one comprising levan as the main matrix forming agent and mannitol or trehalose or raffmose (or combinations thereof) as secondary matrix-forming agent, with levan constituting 10 - 99.99% (all % of ingredient are w/w, meaning weight of mentioned ingredient out of the weight of all 5 constituents of the composition combined), and the secondary matrix forming agent constituting 0 - 89.99%, typically 25-50%. The content of the active ingredient may typically (but not exclusively) be up to 90% of the entire composition. typically in the range of 0.01-70% depending on the nature of the active ingredient. In one embodiment, the active ingredient comprises 0.01-1% out of the entire weight of the composition. in another embodiment, the active ingredient comprises 0,5-2% out of the entire wei ght of the composition. In yet another embodiment, the active ingredient comprises 5-30% out oC the entire weight of the composition. In other embodiments, the active ingredient comprises 20-40% out of the entire weight of the composition. In vet other embodiments, the active ingredient comprises 60-90% out of the entire weight of the composition, In one embodiment, the composition of the invention does not contain fish gelatin. In another embodiment, the composition of the invention does not contain a modified starch. In another embodiment, the composition of the invention does not contain puliulan in combination with an amino acid, In another embodiment, the composition of the invention does not contain maitodextrin in combination with sorbitol. "Disintegration Time" and "Dissolution Time" are used interchangeably herein and should be understood to mean the time needed to dissolve or disintegrate the composition of the invention in an aqueous solution or with saliva within the oral cavity. "Oral dissolving Time" as used herein should be understood to mean the time needed to dissolve the composition of the invention in the oral cavity. "Rapid/Fast disintegrarion/dissolution" as used herein should be understood to encompass disintegration of at least 80% of the composition of the invention, typically 90% and more typically 100% of the composition in an aqueous medium or in saliva (in the oral cavity) within 30 seconds, typically within 10 seconds and at times even within 9, 8, 7, 6, 5, 4, 3, 2 or 1 second, Examples of an aqueous medium as used herein are water or a buffer (e.g. potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium hydrogen 6 phosphate) or artificial saliva as described by Morjaria et. al (May 2004), Dissolution Technologies 12 5- . Saliva as used herein refers to the saliva in the oral cavity of a mammal, in particular a human. "Tensile strength " as used herein should be understood to be the force required to break a tablet, which is measured by the three-point bending test, wherein the tablet is subjected to a bending stress (Mohd et al. 2002), Drug Development and Industrial Pharmacy 28(7):809-813). In one embodiment, a pharmaceutical composition of the invention has a tensile strength in the range of about 0.05 - ,6iN/mm 2 In another embodiment, a pharmaceutical composition of the invention has a tensile strength in the range of about 0.15 - 1.4N/mm 2 In yet another embodiment, a pharmaceutical composition of the invention has a tensile strength in the range of about 0.3-0.85 N/mm 2 . It is envisaged that a pharmaceutical composition of the invention has a rapid disintegration/dissolution rate such that at least 80% of the composition is dissolved in an aqueous medium or in saliva within 30 seconds, typically within 10 seconds. In one embodiment, a pharmaceutical composition of the invention has a rapid disintegration/dissolution rate such that at least 90% of the composition is dissolved in an aqueous medium or in saliva within 30 seconds, typically within 10 seconds. In one embodiment, a pharmaceutical composition of the invention has a tensile strength in the range of about 0.05-1.6 N/mr& and a rapid disintegration/dissolution rate such that at least 80% of the composition is dissolved in an aqueous medium or in saliva within 30 seconds, typically within 10 seconds. In another embodiment, the invention provides a pharmaceutical composition comprising a pharmaceutically active ingredient, having a tensile strength ranging between about 0,15 to 1.4 N/mm2 and a rapid disintegration/dissolution rate such that at least 80% of the composition is dissolved in an aqueous medium or in saliva within 30 seconds, typically within 10 seconds, 7 In another embodiment, the invention provides a pharmaceutical composition comprising a pharmaceutically active ingredient, having a tensile strength ranging between about 0.3 to 0.85 N/mm 2 and a rapid disintegration/dissolution rate such that at least 80% of the composition is dissolved in an aqueous medium or in saliva within 30 seconds, typically within 10 seconds. In one embodiment, a pharmaceutical composition of the invention has a tensile strength in the range of about 0.05-1.6 N/mm 2 and a rapid disintegrationidissoluion rate such that at least 90% of the composition is dissolved in an aqueous medium or in saliva within 30 seconds, typically within 10 seconds. In another embodiment, the invention provides a phannaceutical composition comprising a pharmaceutically active ingredient, having a tensile strength ranging between about 0.15 to 1.4 N/mm 2 and a rapid disintegration/dissolution rate such that at least 90% of the composition is dissolved in an aqueous medium or in saliva within 30 seconds, typically within 10 seconds. In another embodiment, the invention provides a pharmaceutical composition comprising a pharmaceutically active ingredient, having a tensile strength ranging between about 0.3 to 0,85 N/mm2 and a rapid disintegration/dissolution rate such that at least 90% of the composition is dissolved in an aqueous medium or in saliva within 30 seconds, typically within 10 seconds. The open matrix network enables a liquid to enter the dosage form through the interstices and permeate through its interior. Permeation by aqueous media (such as saliva, water, etc.) exposes the carrier material of both the interior and exterior of the dosage form to the action of the aqueous media or saliva whereby the network of carrier material is rapidly disintegrated/dissolved. The open matrix structure is of a porous nature and enhances disintegration of the dosage forn as compared with ordinary solid shaped pharmaceutical dosage forms such as (granulated and compressed) tablets, pills, capsules, suppositories and 8 pessaries. Rapid disintegration results in rapid release of the active ingredient carried by the matrix. In the subject invention, the carrier material of the open matrix network is levan or a derivative thereof. Levan (also named leaven, levulosan. polyfructosan, polyfructose and polylevulan) is a polymer of fructose Cju,. Levan is a polysaccharide with P-(2->6) linkages between the fructose rinas where the numbers describe the carbon atoms in the fructose ring which are linked and the P describes the stereochemical relationship, Levans have also been described as fructans in which the predominant glycosidic linkage between the D- fructofuranoside monomeric units is P-(2->6). The levans are generally made by microorganisms and do not occur as high molecular weight compounds in plants. Some low molecular weight levans having a molecular weight of less than 100,000 Daltons can occur in grasses. Levan" as used herein should be understood to encompass levan derived from any source such as but not limited to A. indicus, A. versicolor, Acetobacter suboxydans, Achromobacter spp., Actinomycenes sp., Actinomyces viscosus, Aerobacter aerogenes, Aerobacter levanicum, Aspergillus sydowi, Azotobacter chroococcun, Bacillus polyrnyxa, Bacillus licheniformis, Bacillus macerans, Bacillus megatherium, Bacillus mesentericus, Bacillus subtilis, Bacillus vulgatus, Corynbacterium laevaniformans, Erwinia herbicola, Gluconobacter oxydans, Leuconostoc mesenteroides, Odontomyces viscosus, Phytobacteriun vitrosum. Phytomonas pruni, Psuedomonas Fluorescens, Pseudomonas Syringae, Pseudomonas prunicola, Rothis dentocariosa, Serratia kiliensis, Steptococcus bovis, Steptococcus Imutans, Steptococcus salivarius, Xanthomonas campestris, Xanthomonas pruni, Zymomonas mobilis and so forth. In a specific embodiment, the levan is obtained from Zvmornonas and Bacillus species, In a more specific embodiment, the levan is obtained from Zymomonas mobilis. It should be understood that also derivatives of levan (e.g. as described in W098/03 184) can be used in place of levan. 9 The pharmaceutically active ingredient may encompass any pharmaceutical ingredient such as a drug, a compound, a peptide, a nucleotide. and so forth. Non-limiting examples of drugs which can be carried by the open matrix network of the subject invention are analgesics, alpha blockers, anti-allergy, anti-asthma, (allergic rhinitis, chronic uticaria), anti-inflammatory, antacids, anthelmintics, anti-arrhythmic agents, anti-arthritis, anti-bacterial, anti-anxiety, anti-coagulants, anti-depressants, anti-diabetics, anti-diarrheals, anti-diuretics, anti-epileptics, anti-fungal, anti-gout, anti-hypertensive, anti-incontinence, anti-insomnia, anti-malaria] s. anti-migraine, anti muscarinic, anti-neoplastic and immunosuppressants, anti-protozoal., anti-rheumatics, anti-rhinitis, anti-spasmatic. anti-thyroid, antivirals, anxiolytics, sedatives, hypnotics and neuroleptics, beta-blockers, anti-benign hyperplasia (BIP). cardiac inotropic, corticosteroids, cough suppressants, cytotoxics, decongestants, diabetic gastric stasis, diuretics, enzymes, anti-parkinsonian, gastro-intestinal, histamine receptor antagonists, infertility, endometriosis, hormone replacement therapy, lipid regulating agents, local anesthetics, neuromuscular agents, nitrates and anti-anginal agents, menstrual disorders, motion sickness, anti-pain, anti-nausea, movement disorders, nutritional agents, opioid analgesics, oral vaccines, proteins, peptides and recombinant drugs, prevention of chemotherapy induced and post operative nausea and vomiting proton pump inhibitors, schizophrenia, sex hormones and contraceptives, seizure/panic disorder, sexual dysfunction (male and female), spennicides, stimulants voiding dysfunctions, veterinary medicines and so forth Specific non-limiting examples of these drugs are: Alfa blockers: Tamsulosine Analgesics and anti-inflammatory agents: aspirin, aloxiprin, auranofin, azapropazone, benorylate, difiunisal, etodolac, fenbufen, feLnoprofen calcium, flurbiprofen, ibuprofen. indomethacin, ketoprofen, melofenamic acid, mefenamic acid, nabumetone, naproxen, oxaprozin, oxyphenbutazone, phenylbutazone, piroxicam, sulindac, paracetamol. Antacids: aluminum hydroxide, magnesium carbonate, magnesium trisilicate, hydrotalcite, dimethicone. 10 Antihelnintics: albendazole, bephenium hydroxynaphthoate, cambendazole, dichlorophen, ivermectin, mebendazole, oxamniquine, oxfendazole, oxantel embonate, praziquantel, pyrantel embonate, thiabendazole. Anti-allergic: des loratidine, loratidine, Montelukast ,Montelukast sodium, Cetirizin. Fexofenadin, Ebastine. Anti-arrhythmic agents: amiodarone HCI, disopyramide., flecainide acetate, quinidine sulphate. Anti-bacterial agents: benethamine penicillin, cinoxacin. ciprofloxacin IHICI, ciarithromycin, clofazimine, cloxacillin, demeclocycline, doxycycline, erythronycin, ethionamide, imipenem, nalidixic acid, nitrofurantoin, rifampicin, spiramycin, sulphabenzamide, sulphadoxine, suipharnerazine., sulphacetamide, sulphadiazine, sulphafurazole, sulpharnethoxazole. sulphapyridine, tetracycline, trimethoprim, Anti-coagulants: dicoumarol, dipyridamole, nicoumalone, phenindione. Anti-depressants: anoxamne, ciclazindol, maprotiline HCl, mianserin HCI, nortriptyline HC1, trazodone HCI, trimiprarnine mnaleate. Anti-diabetics: acetohexamide, chlorpropamide, glibenclamide, gliclazide, glipizide, tolazamide, tolbutamide. Anti-diarrheals: atropine sulphate, codeine phosphate, co-phenotrope, difenoxin, loperamide hydrochloride, suphasolazine, mesalazine, olsalazine, corticosteroids,prednisolone. Anti-diuretics: desmiopressin, desmopressin acetate. Anti-epileptics: beclamide, carbanazepine, clonazepam, ethotoin, methoin, methsuximide, methylphenobarbitone, oxcarbazepine, paramethadione, phenacemide, phenobarbitone, phenytoin, phensuximide, primidone, sulthiame, valproic acid. Anti-fungal agents: amphotericin. butoconazole nitrate, clotrimnazole, econazole nitrate, fluconazole, flucytosine, griseofulvin, itraconazole, ketoconazole, miconazole, natamycin, nystatin, sulconazole nitrate, terbinafine HCl, terconazole, tioconazole, undecenoic acid. Anti-gout agents: allopurinol, probenecid, sulphinpyrazone. Anti-hypertensive agents: amlopidine, benidipine, darodipine, dilitazern HCI, diazoxide, felodipine, guanabenz acetate, indoramin, isradipine, minoxidil, nicardipine HCI, nifedipine, nimodipine, phenoxybenzamine HCi, prazosin HCI, reserpine, terazosin HCL. Anti-insomnia: Zolpidem 11I Anti-malaria: amodiaquine, chloroquine, chloroproguanil HCl, halofantrine HCI, mefloquine HC, proguanil HCI, pyrimethamine, quinine sulphate. Anti-migraine agents: rizatriptan, dihydroergotamine mesylate, ergotamine tartrate, methysergide maleate, pizotifen maleate, sumatriptan succinate, caffeine. Anti-muscarinic agents: oxybutinin, tolterodin, atropine, benzhexol MCl, hiperiden, ethopropazine IC, hyoscine butyl bromide, hyoscyamine, mepenzolate bromide. orphenadrine, oxyphencylcimine HCI, tropicamide, Anti-neoplastic agents and immunosuppressants: aminogluteth imide, amsacrine, azathioprene, busulphan, chlorambucil, cyclosporin, dacarbazine, estramustine, etoposide, lomustine, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, mitozantrone, procarbazine I-Cl, tamoxifen citrate, testolactone. Anti-protozoal agents: benznidazole, clioquinol, decoquinate, diiodohydroxyquinoline, diloxanide furcate, dinitoImide, furzolidone, metronidazoie, ninorazole, nitrofurazone, ornidazole, tinidazole. Anti-rheuniatics: ibuprofen, aceclofenac, acemetacin, azapropazone, diclofenac sodium, diflunisal, etodolac, ketoprofen, indomethacin. mefenamic acid, naproxen, piroxicam, aspirin, benorylate, auranofin, penicillamine. Anti-rhinitis, anti-uticaria: Cetirizin, fexofenadin, ebastine. loratidin, montelukast Anti-spasmatic: phlioroglucinol anhydre Anti-thyroid agents: carbimazole, propylthiouracil. Antivirais: acyclovir, amantadine hydrochloride, faniclovir, zidovadine, didanosine, zalcitabine, foscarnet sodium. Anxiolytic, sedatives, hypnotics and neuroleptics: alprazolam, amylobarbitone, barbitone, bentazepam, broinazepam, bromperidol., brotizolam, butobarbitone, carbromal, chlordiazepoxide, Chliorpheniramine, chlonnethiazole, chlorpromazine, clobazam, clonazepan, clotiazepam, clozapine, diazepam, droperidol, ethinamate, flunanisone, fiunitrazepam, fluopromazine, flupenthixol decanoate, fluphenazine decanoate, flurazepam, haloperidol, lorazepam, lormetazepam, medazepam, meprobamate, methaqualone. midazolam, nitrazepam, oxazepam, pentobarbitone, perphenazine phenylephrine, pimozide, prochlorperazine, pseudoephedrinelICL, sulpride, temazepani, thioridazine, triazolamn, zopiclone. p-Blockers: acebutolol, alprenolol, atenolol, labetalol, netoprolol, nadolo], oxprenolol, pindolol, propanolol. 12 Cardiac inotropic agents: amrinone, digitoxin, digoxin, enoximone, lanatoside C, medi goxin. Corticosteroids: beclomethasone, betamethasone, budesonide, cortisone acetate, desoxymrethasone, dexamethasone, fludrocortisone acetate, flunisolide, flucortolone, fluticasone propionate, hydrocortisone, methylprednisolone, prednisolone, prednisone,tiameinolone. Cough suppressants: codeine phosphate dexomethorphan, ,guaifenesin, pholeodine, diamorphine, methadone. Cytotoxics: ifosfanide, chlorambucil, melphalan, busulphan, cytotoxic antibodies, doxorubicin, epirubicin, plicamycin, bleomycin, inethotrexate,. cytarabine, fludarabine. gencitabine, fluorouracil, roercaptopurine, thioguanine, vincristine, vinblastine, vindesine, etoposide. Decongestants: pseudoephedrine hydrochloride. Diuretics: acetazolamide, amiloride, bendrofluazide, bumetanide, chlorothiazide. chlorthalidone, ethacrynic acid, frusemide, metolazone, spironolactone, triamterene. Enzymes: pancreatin, pepsin, lipase. Epilepsy: Gabapentin Anti-parkinsonian agents: bromocriptine mesylate, lysuride maleate, selegiline, para-fluoroselegiline, lazabemide, rasagiline, 2-BUMP [N-(2-butyl)-N methylpropargylanine], M-2-PP [N-methyi-N-(2-pentyi)-propargylamine, MDL 72145 [beta-(fluoromethylene)-3,4-dimethoxy-benzeneethanamine], mofegiline, apomorphine, N-propylnoraporphine, cabergoline, metergoline, naxagolide, pergolide. piribedil, ropinirole, terguride, quinagolide. Gastro-intestinal agents: bisacodyl, cimetidine, cisapride, diphenoxylate 1CI, domperidone, metociopramide, famotidine, loperamide, mesalazine, nizatidine, esomeprazole. metopimazine, pantoprazole, ondansetron HCI, Granisetron, tropisetron, dolasetron, ranitidine HCl. sulphasalazine. Lanzoprazole, Histamine Receptor Antagonists: acrivastine, astemizole, cinnarizine, cyclizine, cyproheptadine HCI, dimenhydrinate, flunarizine HCI, loratadine. rmecliozine HC. oxatomide, terfenadine, triprolidine. Hormone replacement therapy: dydrogesterone Hypertension: Enalapril Lactation: Oxytocin, oxytocin agonists Lipid regulating agents: bezaibrate, clofibrate, fenofibrate, gemfibrozil, probucol. Local anaesthetics: amethocaine, amylocaine, benzocaine, bucricaine, bupivacaine, butacaine, butanilicaine, butoxycaine, butyl aminobenzoate, carticaine, chioroprocaine, cinchocaine, clibucaine, clonnecaine, coca, cocaine, cyclomethycaine, dimethisoquin, diperodon, dyclocaine, ethyl chloride, ethyl p piperidinoacetylaniinobenzoate, etidocaine, hexylcaine, isobutamben, ketocaine, lignocaine, mepivacaine, meprylcaine, myrtecaine, octacaine, oxethazaine, oxybuprocaine, parethoxycaine, pranoxine, priocaine, procaine, propranocaine, propoxycaine, proxymetacaine, ropivacaine, tolycaine, tricaine, trimecaine, vadocaine. Motion sickness: diphenhydranine Neuro-muscular agents: pyridostigmine. Nitrates and other anti-anginal agents: amyl nitrate, glyceryl trinitrate, isosorbide dinitrate. isosorbide mononitrate, pentaerythritoi tetranitrate. Nutritional agents: betacarotene, vitamins, such as vitamin A, vitamin B 2 , vitamin D, vitamin E, vitamin K, minerals. Opioid analgesics: codeine, dextropropyoxyphene, diamorphine, dihydrocodeine, meptazinol, methadone, morphine, natbuphine, pentazocine. Oral vaccines: to prevent or reduce the symptoms of diseases such as Influenza, Tuberculosis., Meningitis, Hepatitis, Whooping Cough. Polio, Tetanus, Diphtheria, Malaria, Cholera, Herpes, Typhoid, HIV, AIDS, Measles, Lyme disease, Traveller's Diarrhea, Hepatitis A, B and C, Otitis Media, Dengue Fever, Rabies, Parainfiuenza, Rubella, Yellow Fever, Dysentery, Legionnaires Disease, Toxoplasmosis, Q-Fever, Haemorrhegic Fever, Argentina Haemorrhegic Fever, Caries, Chagas Disease, Urinary Tract Infection caused by E. coli, Pneumococcal Disease, Mumps, Chikungunya, Hayfever, Asthma, Rheumatoid Arthritis, Carcinomas, Coccidiosis, Newcastle Disease, Enzootic pneumonia, Feline leukemia, Atrophic rhinitis, Erysipelas, Foot and Mouth disease and Swine pneumonia, or to prevent or reduce the symptoms of diseases caused by Vibrio species, Salmonella species, Bordetella species, H-aemophilus species, Toxoplasmosis gondii, Cytomegalovirus, Chlamydia species, Streptococcal species, Norwalk Virus, Escherischia coli, Helicobacter pylori, Rotavirus, Neisseria gonorrhae, Neisseria meningiditis, Adenovirus, Epstein Barr Virus, Japanese Encephalitis Virus, Pneumocystis caring, Herpes simplex, Clostridia 14 species, Respiratory Syncytial Virus, Klebsiella species, Shigella species, Pseudomonas aeruginosa, Parvovirus, Campylobacter species, R.ickettsia species, Varicella zoster, Yersinia species, Ross River Virus, J.C. Virus, Rhodococcus equi, Moraxella catarrhalis, Borrelia burgdorferi and Pasteurella haemolytica. Voiding dysfunctions: Tamsulosine, trospium chloride, tolterodine , oxybutinin Proteins, peptides and recombinant drugs: recombinant hormones and iso hormones, recombinant cytokines, recombinant plasminogens, TNT receptor fusion protein, monoclonal antibodies, nucleic acids, antsense oligonucleotides, oligonucleotides, glycoproteins and adhesion molecules. Veterinary Arthiritis: Tepoxalin Sex hornnones and Contraceptives: clomiphene citrate, danazol, desogestrel, ethinyloestradiol, ethynodiol, ethvnodiol diacetate, levonorgestrel, medroxyprogesterone acetate, mestranol, methyltestosterone, norethisterone, norethisterone enanthate, norgestrel, estradiol, conjugated estrogens, dydrogesterone, progesterone, stanozolol, stilbocstrol, testosterone, tibolone. Schizoprenia; Olanzapine, Nicergoline Sexual dysfunction: Cabergolin, oxytocin, tadalafil, sildenafil, vardenafil Spermicides: nonoxynol 9. Stimulants: ampheainine, dexanmphetanine. dexfenfluramine, fenfluramine, mazindol, pemoline. In a specific, non-limiting embodiment, the active ingredient is desmopressin acetate. In this embodiment the dosage form can be used in voiding postponement or in the treatment or prevention of incontinence, primary nocturnal enuresis (PNE), nocturia or central diabetes insipidus. In one embodiment, the amount of desmopressin acetate in the composition comprises 0.01 - 2.00 %w/w, In another embodiment, the amount of desmopressin acetate in the composition comprises 0.04 - 1.00 %w/w. In a specific, non-limiting embodiment, the active ingredient is loratidine. In this embodiment the dosage form can be used e.g. for the relief of nasal or non-nasal symptoms of allergic rhinitis and chronic idiopathic urticaria. In one embodiment, the amount of loratidine in the composition comprises 20-40 %w/w. In another embodiment, the amount of loratidine in the composition comprises about 25-40 %w/w. 15 In a specific, non-limiting embodiment, the active ingredient is famotidine. In this embodiment the dosage form can be used e.g. in the treatment of gastroesophageal reflux disease, duodenal and gastric ulcer, pathological hypersecretory conditions (e.g. Zollinger-Ellison syndrome and multiple endocrine adenonas). In one embodiment, the amount of famotidine in the composition comprises 50-90 %w/w. In another embodiment, the amount of famotidine in the composition comprises 60 - 90 %w/w. In a specific, non-limiting embodiment, the active ingredient is montelukast sodium. In this embodiment the dosage form can be used e.g. in prophylaxis and chronic treatment of asthma, allergic rhinitis and exercise-induced bronchoconstriction. In one embodirent, the amount of montelukast sodium in the composition comprises 5-40 %w/w. In another embodiment. the amount of montelukast sodium in the composition comprises 5-30 %w/w. In a specific, non-limiting embodiment, the active ingredient is ondansetron. In this embodiment the dosage form can be used e.g. in the prevention of postoperative nausea and/or vomiting and also in the prevention of nausea and/or associated with cancer chemotherapy and radiotherapy. in one embodiment. the amount of ondansetron in the composition comprises 10-30 %w/w. In another embodiment, the amount of ondansetron in the composition comprises about 20 %w/w. A pharmaceutical dosage form of the invention disintegrates, thereby releasing the active ingredient, upon contact with a fluid (an aqueous medium or saliva). Typically, a pharmaceutical dosage form of the invention is an orodispersible pharmaceutical dosage form which disintegrates in the mouth within 30 seconds, typically 10 seconds or less. The term "rodipersibe" as used herein should be understood to encompass a solid dosage form which disintegrates or dissolves in the mouth within (at most) 30 seconds. In further embodiments, the orodispersible dosage form disperses in the mouth within 10, 9, 8, 7, 6, 5, 4, 3, 2, or even within I second. 16 A suitable route of administration for the dosage form of the subject invention is oral administration including buccal and sublingual administration. In a specific embodiment, the dosage form is administered sublingually. Dosage forms of the invention may also be placed on the tongue or against the cheek or gingiva. Pharmaceutical dosage forms of the present invention are adapted to supply the active ingredient to e.g. the oral cavity. The active may be absorbed across the mucosa at the site of administration, e.g. sublingual mucosa, and/or otherwise, in the case of oral administration, from the oral cavity (e.g. across the buccal and/or gingival mucosa) and/or from the gastrointestinal tract for systemic distribution. The exact dose and regimen of administration of the dosage form will necessarily be dependent upon the therapeutic effect to be achieved and may vary with the particular active ingredient, the route of administration, and the age and condition of the individual subject to whom the medicament is to be administered. At times patients may be instructed to take two or any other number of unit dosage forms in a single administration or at tires only a portion, such as half or a quarter of the unit dosage form in a single administration. The dosage forn of the invention achieves a balance of performance: tensile strength, stability and fast disintegration. It may be produced by known lyophilisate technology, It can be stored (and packed) in blisters but due to its tensile strength, can also be stored and/or packaged in bottles or bulk. The invention achieves these results in a single processing step, without the need to resort to multiple steps including granulation. In addition to the ingredients previously discussed, the matrix may also include other excipients (auxiliary agents, accessory agents) such as, but not limited to fillers, matrix-forming agents, thickeners (including but not limited to guar gum and xanthum gum), binders, diluents, lbricants, p1H adjusting agents, protecting agents, viscosity enhancers, wicking agents, non-effervescent disintegrants, effervescent disintegrants, surfactants, anti-oxidants, wetting agents, colorants, flavouring agents, taste-masking agents, sweeteners, preservatives and so forth. 17 In one embodiment, a composition of the invention is obtainable by subliming solvent from a liquid preparation comprising an active ingredient, levan and optionally secondary matrix forming agents) in a solvent. Typically, the liquid preparation is placed in a mould, e.g. such that following sublimination a solid composition, typically in a dosage unit, is formed within the mould. The mould can be an open blister pack whereby the solid dosage unit is formed within the blister pack's depression which is thereafter sealed by a sealing film or foi. In one embodiment, the process comprises introducing unit dosage quantities of said preparation into depressions of an open blister pack; and then subliming the preparation to obtain solid dosage forms within said depressions. The sublimation can be carried out by freeze drying the preparation comprising the active ingredient, levan and optionally secondary matrix forming agent(s) in a solvent. In one embodiment, the solvent is water. The invention thus discloses a process for preparing fast-dispersing dosage forns by lyophilizing a combination of an active ingredient, levan and optionally secondary matrix forming agentss. The fast-dispersing dosage form contains a network of the active ingredient and the carrier levan and optionally the secondary matrix forming agent(s), the network having been obtained by subliming solvent from the liquid preparation that contains the active ingredient, levan and the other optional matrix forming agents. Said preparation may be a solution, suspension or dispersion. Typically, an initial preparation comprising an active ingredient, levan and optionally secondary matrix forming agent(s) in a solvent is prepared, followed by sublimation. The sublimation can be carried out by freeze drying the preparation. In a freeze drying procedure, the preparation (in liquid form) that comprises an active ingredient, levan and any other optional matrix forming agent in a solvent is filled into moulds. Each mould typically contains a defined amount of such solution with a defined amount of active ingredient. The preparation in the mould is then frozen, for example by passing gaseous cooling medium over the mould. After the preparation has been frozen, the solvent is sublimed therefrom, The sublimation is carried out in a 18 freeze dryer. In consequence an open matrix network of levan optionally together with other matrix forming agents included in the solution, carrying the active ingredient, is thereby formed. The preparation is contained in a mould during the freeze-drying process to produce a solid form in any desired shape. Prior to the lyophilization, the mould may be cooled and frozen (e.g. in a fast-freeze tunnel or on the shelves of the lyophilizer), for example using liquid nitrogen or solid carbon dioxide, In one embodiment, the freezing rate is from 0.1 to 2 0 C/minute. In another embodiment, the freezing rate is from 0.5 to 1.5 0 C/minute. In yet another embodiment, the freezing rate is from 10 to 260"C/minute, In another embodiment, the freezing ra t e is from 20 to 260C/mrinute. In a further embodiment, the freezing rate is from 20 to 160"C/minute. After lyophilization, the freeze dried compositions can either be removed from the mould if desired or stored therein until later use. Typically, each mould is so designed so to produce a unit dosage form of the composition. The composition so obtained is fast-dispersing and disintegrates within at most 30 seconds upon contact with fluid, typically within less than 10 seconds. The solvent is typically water but may optionally also contain a co-solvent (such as an alcohol e.g. tert-butyl alcohol) to improve the solubility of the chemical, The composition may contain a pH adjusting agent to adjust the pH of a solution from which the dosage form is prepared within the range of from 2 to 10, typically from 3.5 to 9.5 or from 4.5 to 8. Citric acid, sodium hydroxide, and sodium carbonate can be used as pH adjusting agent, but others including hydrochloric acid and malic acid can also be used. Non-volatile pH adjusting agents will not be removed by freeze drying or other sublimation processes and so may be present in the final product. When preparing a fast dissolving dosage form of the invention using the main matrix forming agent levan without adding secondary matrix forming agents, an annealing process (temperature shifts) may be used during the lyophilization process in order to smoother the surface of the dosage form. Such an annealing step is carried out for an esthetic purpose only and has no influence on the dissolution time nor on the tensile 19 strength of the resulting dosage form. When secondary matrix forming agents are present, there is no need for such a smoothing annealing step. The mould may comprise a series of cylindrical or other shape depressions in it, each 0f a size corresponding to a desired size of a dosage form to be formed. In one embodiment, the mould is a depression in a sheet of filmic material. The filmic material may contain more than one depression, The filmic material may be similar to that employed in conventional blister packs which are used for packaging oral contraceptive tablets and like medicament forms. For example the filmic material may be made of thermoplastic material with the depressions formed by thermoforming or coldforming. Polyvinyl chloride film can be used as filmic material. Laminates of filmic material may also be used. EXAMPLES The invention is further described in the following examples, which are not in any way intended to limit the scope of the inventions as claimed, A. Materials used in the examples presented below Material [Obtained from Levan (Zymomnonas spp) RealBiotech, Korea SLevan (Bacilus spp.) Montana Polysaccharides, USA Citric acid Merck, India Mannitol Merck, India Desmopressin acetate Manufactured by Polypeptide Labs A/S, and supplied by Ferring Loratadine Ultratech India Ltd Famotidine Exim Pharma International, India Montelukast Sodium MSN Pharma Chem Pvt. Ltd., India Ondansetron base Cadila Pharma Ltd., India Guar gum Merck, India Sodium lauryl sulphate (SLS) Merck, India Xanthan gum SD Fine Chem Ltd., India 20 Sodium citrate Merck, India Pullulan Hyashibara. Japan Glycine Sigina Aldrich lydropropvl methyl cellulose (HPMC) Shin-Eisu Chemical Co. Japan Methyl cellulose Shin-Etsu Chemical Co. Japan Gum tragacanth Merck, India Fish gelatin Croda Chemicals Pv Ltd., India Sodium methyl paraben Alta Lab Pvt. Ltd., India Raffinose Loba Chemie Pvt. Ltd, India Trehalose Loba Chemie Pvt, Ltd., India Sodium propyl paraben Prayosha Healthcare. India Hydroxy propyl j cyclodextrin Gangwal Chemicals Pvt. Ltd., India Sodium hydroxide Merck, India Neotame Nutrasweet, USA Strawberry flavour Virginia Dare, USA Cherry flavour Virginia Dare, USA B. Method for preparing Placebo formulation 1) Dissolve Levan, and other excipients, if present, in purified water under stirring at 200 to 500 revolutions per minute (rpm). 2) Optionally adjust the pH of the solution using citric acid solution or NaOH. 3) Make up the final volume of the solution using purified water. 4) Mix the solution under stirring at 200 to 500 rpm for 15 minutes. 5) Dose the solution into each cavity of preformed blister sheets (typically using dispensing pipette). 6) Freeze the filled blisters at a temperature in the range of -20 to -Il 0"C 7) Freeze dry the blisters in a lyophilizer 8) Place the blister sheet containing dried lyophilisates on the punched carrier web of a blister packaging machine to transport the blister sheets through the sealing station of the packaging machine. 9) Seal the blisters with a lidding foil and punch into final blisters. 21 CL Formulations The following formulations were prepared using the method described in the method section "B" above, by freezing the blisters at the rate of 0.1 2 "C/minute in step 6. Example - I Component Amount i unit | % ww Levan (Bacilusspp.) 25mg 100 Purified water q s to 2 50 pl Example - 2 Component Amount / unit % wlw Levan (Zymomonas spp.) 25mg 100 Purified water q.s to 250pl Example - 3 Component Amount / unit % w/w Levan (Bacilus spp.) 37.5mg 100 Purified water cs to 250l Example - 4 Component Amount / unit % w/w Levar (Zy.momnonas spp.) 37.5mg 100 Purtlied water q.s to 2 50gl Example - 5 Component Amount / unit % w/w Levan (Zvmomonas spp.) 18.75img 100 Purified water q.s to 250t Example - 6 Component Amount / unit % w/w Levan Zvmomonas app.) 12.5mg 100 Purified water q.s to 250d 22 Example - 7 Component Amount / unit % w/W Levan (Zymomonasspp.) 18.75mg 99.99 Citric acid (5%w/v) q.s to pH 4.5 qs to pH 4,5 Purified water q.s to 250pl Example - 8 Component Amount / unit % w/w Levan (Zymnomanas spp) 18.75mg 99.99 Citric acid (5%w/v) q.s to pH 5.0 q.s to pH 5.0 Purified water q s to 250pl Example - 9 Component Amount / unit % w/w Levan (Zymomonas spp ) 25mg 99.99 0. IN NaOl q.s to pH 7.0 q. s to pI 7.0 Purified water q.s to 250p1 Example -10 Component Amount / unit % w/w Levan (Zymomonas spp ) 25mg 99.99 0.INNaOH q q.s to pH 8,0 Purified water q.s to 250pl Example - 11 Component Amount / unit % ww Levan (Zynomnas spp.) 25mg 99.99 0.IN NaOH q.s to PH 9.0 q.s to pH 9.0 Purified water q.s to 250 41 23 Example-12 Component Amount/unit % w/w Levan (Zymononas spp.) 18.75mg 75 Mannitol 6.25m 25 Purified water q.s to 2 5 0 p 1 Example-1 3 Component Amount/unit % w/w Levan (Zymomonas spp) 125in 50 Mannitol 1 i5mg 50 Purified water q.s to 250pl C2 Formulations The following formulations were prepared using the method described in "B herein above, by freezing the blisters a- a rate of 20 - 160TC/minute in 4 minutes in step 6. Example-14 I opponent Amount/unit % w/w Levan (Zymnomonas svp.) 25mg 100 Purified water q.s to 25 0p Example-i 5 tomuponent Amount/unit % w/w Levan (Zyonmonas spp.) 25mg 99.99 Citric acid (5%w/iv) q.s to p1I 4.5 q.s to pH 4.5 Purifed water q.s to 250vd Example-16 Component Amounri/nit % w/w Levan (Zymomonas spp.) 16.

2 5rng 64.99 Mannitol 8.75mg ; 34.99 Citric acid (5%w/v) qs to pL 4.0 q.s to pH 4.0 Purified water q.s to 2501 24 Example-17 Component Amount/unit % w/w Levan (Zymomonas spp) 16.25mg 64.99 Mannitol 8.75mg 34.99 Citric acid (5%w/v) q.s to p' 1 4.5 q.s to p 145 Purified water q.s to 250pIl Example-Is Component Amount/unit % w/w Levan (Zymomonas spp) 16.25mg 64.99 Mannitol 8.75mg 499 Circ acid (5%wv)s to pH 5.0 q.s to pH 5.0 Purified water qs to 250p Example-19 Component Amount/unit % wiw Levan (Zymnomonas spp.) 12.5mg 4999 M4annio 12.5mg 49.99 Citric acid (5%w/v) q s to pH 4.5 q s to p-I 4,5 i ied water qrs to 2 5 0 pi Example-20 Component Amoumt/unit % w/w Levan (Zymotnonas spp.) 18.75mg 74.99 Mannitol 6.25mg 24.99 Citric acid (5%wv) qs to pH 4.5 q.s to p1 4.5 Purified water q.s to 250pl 25 Example-21 Component Anount/unit % w/w Levan 7ymomnonasnspp.) 18.75mg 75.0 Raffinose 6 25mg 25.0 Purified water qas to 250pd Example-22 Component Amount/unit % w/w Levan (Zymomonas spp.) 18.75mg 74.99 Trehalose 6.25mg 24.99 Citric acid (5%w/v) q.s. to pH 4.5 qs to pH 4.5 Purified water q.s to 250pl D. Method/fr preparing dosage forms containing Desmopressin I) Dissolve Levan, and other excipients, if present, in purified water under stirring at 200 to 500 rpm; 2) Dissolve Desmopressin acetate in purified water and add to the solution prepared in step 1. 3) Adjust the pH of the solution using citric acid solution (5% w/v). 4) Make up the final volume of the solution using purified water. 5) Mix the solution under stirring at 200 to 500 rpm for further 5 - 15min. 6) Dose the solution into cavities of preformed blister sheets (typically using dispensing pipette). 7) Freeze the filled blisters at a temperature in the range of -20 to -11 1 OC 8) Freeze dry the blisters in a lyophilizer 9) Place the blister sheet containing dried lyophilisates on the punched carrier web of the blister packaging machine, to transport the blister sheets through the sealing station of the packaging machine. 10) Seal the blister with a lidding foil and punch into final blisters. E. Desmopressin Formulations The following desmopressin lyophilisate formulations were prepared using the method described in "D" above, by freezing the blisters at the rate of 0.1-2 0 C/minute or 20-160 0 C/minute in step 7. 26 Example- 2 3 Component Amount/unit % w/w Desnopressin acetate 240gg 0.63 equivalent to Desmopressin Levan (Bacilus spp.) 37.5mg 99.36 Citric acid (5%w/V) 9.s to pH 4 q.s to p1H 4.5 Purified water q.s to 250 pl Example-24 Component Amountlunit 1 % w/w Desmopressin acetate 240 pg 1.3 equivalent to Desmopressin SLevan (Zvmomonas spp) 18.75mg 98.7 Citric acid (5%w/v) q.s to pH 4.5 qps to pH 45 Purified water q.s to 250 au Example-25 C Amount/unit % w/w Desmopressin acetate j 240 pg 113 equivalent to Desmopressin --.----------.--- --- - Levan (Zymomonas spp) 18.75mg 98.7 Citric acid (5%w/v) q.s to pH 5.0 qps to pH 5.0 Purified water q.s to 250 p[d Example-26 Component Amount/unit % w/w Desmopressin acetate 240pg 0.95 equivalent to Desmooressin Levan (Zyrnomonas spp.) 16.25mg 64.4 Mannitol 8.75mg 34.7 Citric acid (5%w/v) q.s to -pH 4.5 q.s to pH 4.5 Purified water q.s to 250 p1 L ---------------------- ------ ---------- 27 27 Example-27 Component Amount/unit % w/w Desmopressin acetate 240g 1.26 equivalent to Desmopressin Levan (2ymomonas spp.) 18.75mg 98.73 Sodium Citrate buffer (2.5 mM) q.s to pH 4.5 q.s to pH 4.5 Purified water q.s to 250 p Example-28

--------------------

Component Amount/unit % w/w Desmopressin acetate 240ig 1.26 equivalent to Desmopressin Levan (Zvmononas spp.) 1 18.75mg 98.73 Sodium Citrate buffer (5.0 mM) q.s to pH 4.5 q.s to pH 4,5 water q.s to 250 ld Example-29 Component Amountunit % w'w Desmopressin acetate 2 4 0pg 0.79 equivalent to Desmopressin Levan (Zymomonas spp) 19.5mg 64.48 Mannitol 10,5mg 34.72 Sodium Citrate buffer (5.0 mM) q.s to pH 4.5 q.s to pH 4.5 Purified water q.s to 250 pl Example-30 Component Anount/unit % w W Desmopressi acetate 60tg 0.19 equivalent to Desmopressin Levan (Zymomionas spp.) 19.5mg 64.87 Maritol 10.5mg 34.93 Citric acid (5%v/v) q.s to pH 4.5 q.s to pH 4,5 Purified water q.s to 250 p 28 Example-31 Component Amount/unit % w/w Desmopressin acetate 25pg 0.08 equivalent to Desmopressn Levan (ZyomYonas spp15mg 64.94 Mannitol 10.5mg 34.97 C itic acid (5%wv) qs to pH 4,5 q s to pH 4.5 Purified water jqs to 250 pl Example-32 Component Amount/unit % w/w Desmopressin acetate 10 g 0.03 equivalent to Desropressin Levan (Zy omonas spp.) 19.5mg 64.97 Mannitol 10.5mg 34.99 Citric acid (5%w/v) q s to pH 4.5 q s to pH 4,5 Purified water q .s to 250 pi F. Method for preparing dosage forms containing Loratadine I) Disperse guar gum in purified water under stirring. 2) Prepare solution of levan and other recipients in water under stirring, and add this solution in the guargum solution obtained in step I under stirring at 200 - 500 rpm. 3) Add loratadine to the solution obtained in step 2 under continuous stirring at 200 - 500 rpm. 4) Homogenize the Loratadine suspension for 10 --- 20 minutes to form a uniform suspension. 5) Adjust the pH of the suspension using citric acid solution (5% w/v). 6) Make up the final volume of the suspension using purified water. 7) Mix the suspension under stirring at 200 to 500 rpm for further 5 - 15min. 8) Dose prepared suspension into each cavity of preformed blister sheets with intermediate stirring of the suspension to maintain uniformity. 9) Freeze the filled blisters at a temperature in the range of -20 to -1 10C 29 10) Freeze dry the blisters in a lyophilizer 11) Place the blister sheet containing dried lyophilisates on the punched carrier web of the blister packaging machine, to transport the blister sheets through the sealing station of the packaging machine. 12) Seal the blister with a lidding foil and punch into final blisters. G, Loratadineformulations The following Loratidine lyophilisate formulation were prepared using the method described in "F" above, by freezing the blisters at the rate of 0.1-2 "C/minute or 20 160"C/minute in step 9. Example-33 Component Amount/unit % w/v Loratadine 10 mg 28.5 Levan (Zynornonas spp. 25 mg 70.5 Guargum 0.437 mg 0.01 Citric acid (5%wv) q.s to pH 4.3 q.s to pH 4.3 -__ _ _ _ _ --__ _ __ - _ - -- ----------------------- Purified water q.s to350 pl Example-34 Component Amount/unit % w'w Loratadine 10 mg 35.8 Levan (Zynomonas spp.) 17.5 mg 62.6 --------- ---------------- -- ---------------------- Guargum 0,437 mg 0.01 Citric acid (5%w/v) qIs to pH 4.8 q.s to pH 4.8 Purified water - q.s 350 p1 30 Example-35 Component Amount/unit % w/w Loratadine 10 mg 35.7 Levan (Zymomonas spp.) 17.5 mg 62.4 Guargum 0.437 mg 00 SLS 0.087 mg 003 Citric acid (5%w/v) qs to pH 4,8 qs to pH 4.8 Purified water q.s 350 Id H. Methodfor preparing dosage forms containing Famatidine 1) Disperse xanthan gum or guar gum in purified water under stirring. 2) Dissolve levan in the solution obtained in step I under stirring at 200 - 500 rpm. 3) Add Famotidine to the solution of step 2 under continuous stirring at 200 500 rpm till proper suspension is formed. 4) Homogenize the Famotidine suspension obtained in step 3 for 10m in to form uniform suspension. 5) Adjust the pH of the suspension using 0, IN NaOH, 6) Make up the final volume of the suspension using purified water. 7) Mix the suspension under stirring at 200 to 500 rpm for father 5 - 15min. 8) Dose prepared suspension into each cavity of preformed blister sheets with intermediate stirring of the suspension to maintain uniformity. 9) Freeze the filled blisters at a temperature in the range of -20 to -110CC 10) Freeze dry the blisters in a lyophilizer 11) Place the blister sheet containing dried lyophilisates on the punched carrier web of the blister packaging machine, to transport the blister sheets through the sealing station of the packaging machine. 12) Seal the blister with a bidding foil and punch into final blisters, L Fano/idineformulations The following Famotidine orodispersible dosage forms were prepared using the method described above in "H", by freezing the blisters at the rate of 0.1-2 0 C/ninute or 20-160"C/minute in step 9. 31 Example -36 Component Amount/unit % w'w Famotidine 20 mg 65.5 Levan (Zymornonas spp 10.5 mg 34A Xanthangum 0.023mg 0.07 . IN NaOH q.s to pH 8.0 q.s to pH1 8.0 Purined water q.s 250 pl Example - 37 Component iAmount/unit % w/w Famotidine 20 mg 60,8 Levan (Zymomonas spp.) 12.5 mg 38.0 Xanthangum 037mg 11 0.NNaOH q s to pH 8.0 q.s to pH 8.0 Furined water q s 250 p Example - 38 Component Amount/unit % w/w Famotidine 20 mg 6 5,10 Levan (Zymononas spp.) 10.5 mg 34 18 Xanthangun 0.219mg 0,71 0.1N NaOH q.s to pH 8.0 q.s to pH 8,0 Purified water q.s 250 pl Example - 39 Component iAmount/unit % w/w Famotidine 40 mg 88.03 Levan (Zymomonas spp.) 5 mug 1 1.00 Guar gum 0437mg 0 96 0 IN NaOH q s to pH 8.0 q~s to pH 8.0 Purified water q s 250 pl 32 J Method for preparing dosage forms containing Montelukast sodium 1) Dissolve Montelukast in purified water tinder stirring. 21 Dissolve Levan, and other excipients if present, in the Montelukast solution of step 1 under stirring at 200 -- 500 rpm. 3) Make up the final volume of the solution using purified water. 4) Mix the solution under stirring at 200 to 500 rpm for further 15mm. 5) Dose the solution into each cavity of prefbrmred blister. 6) Freeze the filled blisters at a temperature in the range of -60 to -80"C. 7) Freeze dry the blisters in a lyophilizer 8) Place the blister sheet containing dried lyophilisates on the punched carrier web of the blister packaging machine, to transport the blister sheets through the sealing station of the packaging machine. 9) Seal the blister with a lidding foil and punch into final blisters. K. Montelukast sodiumformulations The following Montelukast orodispersible dosage forms were prepared using the method described in "J" above, by freezing the blisters at the rate of 0.1-2 0 C/minute or 20- 60IC/minute in step 6. Example-40 Component Amount/unit % w/ vw Montelukast Sodium 10mg 28.57 equiva ent to Montelukast Levan 25mg 71.42 Purined water us to 250u Example-41 Component Anount/unit I% w/w Montelukast Sodium 10mg 28.57 equivalent to Montelukast Levan 18.75mg 53.57 Mannitol 6-25mg 17.85 --- -------------------- - ---- - I- - -- - - - - - - Purified water q.s to 250 i -- _ ___ ---- _ ------------------- 3 3 33 Example-42 Component JAmount/unit % wK7 /w Montelukast Sodium 10mg 27.93 equivalent to Montelukast Levan 18.75mg 52.37 Mannitol 6.25mg 17.45 Neotame 0.3mg 0.83 Cherry flavour 0.5mg 19 Puriied water qas to 250 K Example-43 Component Amount/un t % w/w Montelukast Sodium 10mg 27.93 equivalent to Montelukast Levan 1 8.75mg 52 37 Manitol 13.5mg 17.45 -- vd-x -r y - - - ---------- - - - -------- - - - ---------------------------------------- Hydroxy Propyl p.11.3mg cyclodextrin Neotame 0.3mg 083 Cherry flavour 0.5mg 1 39 Purliied water q.s to 250 p Example-44 Component kmount/unit % w/w Montelukast Sodium 10mg 17.84 equivalent to Montelukast Levan 18.75mg 33 .45 Mannitol 424.97 Trehalose 12.5mg 22.30 Neotame 0.3mg 0.53 Cherry flavour 0.5mg 0.89 Purified water q.s to 250 sl 34 Example-45 Component Amount/unit I% w/w Montelukast Sodium 4.0mg 1364 equivalent to Montelukast Leva185mg 63.94 Mannal 6.25mg 21.31 Neotame 0.12mg 0.41 Cherry flavour 0.2mg 0.68 Purified water q.s to 250 pl Example-46 Component Anount/unit % w/w Montelukast Sodium 4.0mg 8.06 equivalent to Montelukast Levan 18.75mg 3782 Mannitol 14.0mg 28.24 Trehalose 12.5mg 25.21 Neotame 0.12mg 0.24 Cherry flavour 0.2mg 0,41 Purified waler q.s to 250 pA Example-47 Component Amount/unit % w/w Monteukast Sodium 5.0mg 9.89 equivalent to Montelukast Levan 18.75mg 37.08 Mannitol 14.0mg 27.68 Irehalose 12.5mg 24.72 Neotame 0.12mg 0.23 Cherry flavour 0.2mg 0.39 Purified water q.s to 250 pl 35 L, MetAhod for preparing dosage forns containing Ondansetron 0) Dissolve levan, mannitol, methyl parabens, propyl parabens, pH adjusting agent., sweeteners and/or flavours in purified water under stirring. 2) Disperse Ondansetron under stirring at 200 - 500 rpm in the solution obtained in step I 3) Make up the final volume of the solution using purified Water, 4) Mix the solution under stirring at 200 to 500 rpm for further 15 minutes. 5) Dose the solution into each cavity of preformed blister. 6) Freeze the filled blisters at a temperature in the range of -60 to -80C. 7) Freeze dry the blisters in a lyophilizer. 8) Place the blister sheet containing dried lyophilisates on the punched carrier web of the blister packaging machine, to transport the blister sheets through the sealing station of the packaging machine. 9) Seal the blister with a lidding foil and punch into final blisters, M. Ondansetron formulations The following Ondansetron orodispersible dosage forms were prepared using the method described in "L" above, by freezing the blisters at the rate of 0.1 2 0 C/minute or 20-160C/minute in step 6. Example-48 Component Amount/unit % w/w Ondansotron 8.0mg 20,64 Levan 24.0mg 61.94 Mannitol 6.

2 5 n 16. 12 Methyl paraben 0.133mg 034 Propyl paraben 0.016mg 0.04 Neotame 0.1mg 0.26 Strawberry flavour 0.25mg 0o64 Purified water q.s to 250 pd 36 Example-49 Component Amount/unit % w/w Ondansetron 8.0mg 20.72 Levan 24,0mg 62.18 Mannitol 6.25mg 16.19 Neotame 0.1mg 0.26 Strawberry flavour 0.25mg 0.65 0. IN NaOH q.s to p11 8.0 q s to pH 8.0 Purified water q.s to 250 gI A. Comparative Exam-ples Example - 50 Comparative lyophilisates were prepared according to the method described in "B" herein above, but using pullulan in place of levan and freezing the blisters at the rate of 20-260*C/mrrinute in:5 4 minutes in step 6. Component Amount/unit % wiw Pullulan 25mg 100 Purified water q.s 250 1 Example - 51 Comparative lyophilisates were prepared according to the method described in "' herein above, but taking -IHPMC in place of 1evan and freezing the blisters at the rate of 0,1.2 "C/minute in step 6. Component Awountunit % w/w HPMC 25mg 00 Purified water q.s 250 p Example - 52 Comparative lyophilisates were prepared according to the method described in "B" herein above, but taking HPMC in place of levan and freezing the blisters at the rate of 20-160 0 C/minute in 5 4 minutes in step 6. 3 7 Component jAmounit/unit% --- ------- - ---- ------ - -- - I --- - -- - - - - - --- - --- ------ IIPMC 25mg 100 Purified Water q ~s 250 l Example - 53 Comparative lyophilisates were prepared according to the method described in "B" herein above, but taking methyl cellulose in place of levan and freezing the blisters at the rate of 0.1 --- 2 0 C/rninute in step 6. Component Amount/unit % w/w Methyl cellulose 25mg [100 Purified water q.s 250 [ Example - 54 Comparative lyophilisates were prepared according to the method described in "B" herein above, but taking methyl cellulose in place of levan and freezing the blisters at the rate of 20 - 160 0 C/minute in 4 minutes in step 6. Component Amount/unit % w w Mtyl Cellulose 25mg 100 Purified water q.s 250 pl Example - 55 Comparative lyophilisates were prepared according to the method described in "B" herein above, but taking gum tragacanth in place of levan and freezing the blisters at the rate of 0.1 - 2 C/minute in step 6. Component Amount/unit I% w/w Gum tragacanth 25mv 00 Purified water q.s 250 p1 Example - 56 Comparative lyophilisates were prepared according to the method described in "B" herein above, but taking gum tragacanth in place of levan and freezing the blisters at the rate of 20 - 160C/minute in 4 minutes in step 6. 38 Component Aniount/unit % w/w Gumtraganh 125mg10 Purified wtr qs 20p Example - 57 Comparative iyophilisates were prepared according to the method described in "B" herein above, but taking Fish gelatin in place of levan and freezing the blisters at the rate of 0.1 - 2 C/minute in step 6. Component Amount/unit % w/w Fish gelatin 25mg 100 Purified water q.s 250 pl The lyophilisates obtained were very fragile and were broken into smaller pieces. No farther analysis could be carried out. Example - 58 Comparative lyophilisates were prepared according to the method described in "B" herein above, but taking Fish gelatin in place of levan and freezing the blisters at the rate of 20 - 160 0 C/minute in 4 minutes in step 6. Component Amount/unit w/wIA Fih gelatin 25mg too Purified water q~s 250 pl1 Example - 59 Comparative lyophilisates were prepared according to the method described in "B" herein above, but taking Fish gelatin in place of lean and freezing the blisters at the rate of 0.1 - 2 0 C/minute in step 6. Component Amount'unit % w/w Fish gelatin 12.5mg 50 Mannitol 12.5mg 50 Purified water q.s250 p 39 Example -60 Comparative lyophilisates were prepared according to the method described in "B" herein above, but taking ish gelatin in place of levan and freezing the blisters at the rate of 20 - 1604C/ninuate in 4 minutes in step 6. Component Anount/unit % w/w Fish gelatin 12.5mg 50 Mannitol 12.5mg 50 Purified water q.s 250 pl 0. Disintegration Tests Oa. Disintegration test in petri dish This test measures the expected disintegration time of a composition of the invention in an aqueous medium which is an indication of its disintegration time in saliva, The disintegration rate of all the lyophilisates on a wet filter paper was determined according to the method described in PCT application W02009002084, page 12 paragraph 129, wherein the test was performed at a temperature of about 25 i 2 C. Ob. Measurement of Oral Dissolving Time (ODT) of Placebos The dissolving time oF the placebo lyophilisates in the oral cavity was determined according to the method described in PCT application W02009002084, page 12 paragraph 132, wherein the lyophilisate was placed on the tongue of a healthy human adult and then measuring the time for it to completely dissolve while rubbing the lyophilisates between the tongue and the upper palate. The mean ODT was calculated from the data obtained from 5 healthy human adults. R Method for testing Disintegration time (Invitro DT) This test measures the disintegration time of the compositions of the invention in aqueous medium which is an indication of their disintegration time in saliva. Equipment : Electrolab, Model : ED2 SAPO Procedure: The method was followed as per USP 31-NF 26 (General Chapters, <701>Disintegration) and Ph Eur. 1997 (2.9.1. Disintegration of tablets and capsules). Water was filled into the beaker and maintained at 37*C ±0.5 C using water bath. The lyophilisates were iaced in sinker made up of copper wire with diameter of about 40 0.5mm (+0.05mm) and length of about 15mm. The lyophilisates were then placed into the basket of basket rack assembly and instrument was set on. The disintegration time was noted in seconds. Q. method testing Tensile strength for Equipment : Engineering Systems (NOTTM) Ltd, Model : 5 kN Testing Machine Procedure: The method for determining tensile strength was fed into the instrument. The parameters test speed (15 mm/min), fracture mode, unit (Newton, [NJ), fracture percentage (80%), low limit (0,1), and distance between the supporting edges (4.5 mm)were set into the instrument. A load cell of 10 kg was used and the tensile strength was calculated using the following formula: N/mm2 = 3 x Mean (N) x Distance between two suporting axis in mm 2 x (Thickness in mm) 2 x (Diameter in mm) Thickness and diameter were determined using vernier calliper. Tensile strength of commercially available Nirnuhd-MD, an orodispersible tablet of Nimesulide prepared by conventional compression technique was found to be 1.14 N/mm R. Dissolution method This test measures the dissolution (%) of an active ingredient f-om a composition of the invention in aqueous medium which is an indication of the release rate of the active ingredient from the composition. Equipment : Varian, Model: VK7025 Procedure: The dissolution time of the lyophilisates containing an active ingredient was measured as follows: The method was followed as per USP 32-NF 27 (General Chapters, <711>Dissolution). Dissolution media (0-lN HCl, Phosphate buffer pH 6.8, Acetate buffer pH 4.5, or 0.5% SLS in water) was selected on the basis of the active ingredient in the composition. Dissolution bowls were filled with appropriate media volume (500mL or 900mL) on the basis of the active ingredient in the composition and the temperature of the media was maintained at 37 0 C ±0.5*C using water bath. The apparatus used was USP type II (Paddle) and set at the required rpm (50rpm) as per the test procedure. Samples were withdrawn as per the time point (5 41 min, I 0min, 15min, and 30min) defined in the test procedure. Samples were analyzed chromatographically or by UV as per the test procedure and % release was calculated. The disintegration rates, ODT, in-vitro DT, tensile strength and Dissolution data for the lyophilisates prepared according to examples I to 37, and comparative examples 38 to 48 are presented in table I Table I Example Disintegration Oral inItro DT Tensile Dissolution No test in petri dissolving (see) strength (5 / 15 dish (see) time (sec) (N/mm) minutes) (%) 7 5 107 NA 2 4 6 12 1.58 NA 3 5 6 4 1.41 NA 4 8 7 5 38 NA 5 3 5 4 0.61 NA 6 2 2 3 0.22 NA 7 4 5 3 0.64 NA 5 5 3 073 NA 9 2 3 4 022 NA 0 2 ------------ 4 4 0,21 NA 14 - .8 NA 2 4 0.44 NA 13 5 4 023 NA 14 2 4 3 0.32 NA 15 4 6 20.7 NA 16 2 4 4 0.09 NA 17 3 3 3A 18 4 3 3 ,09 NA 19 5 4 13 0.07 NA 20 2 4 14 116 NA 42 Example Disintegration Oral In-vitro DT i Tensile Dissolution No test in petri dissolving (see) strength (5 / 15 dish (see) time (see) (N/mm) minutes) 21 22 2 0.16 NA 22 3 4 0,10 NA 23 NA 3 0.32 98/99 24 6 NA 4 08 85/96 25 6 NA 3 0.64 99/99 26 4 NA 010 76/92 27 4 NA 0.84 8795 28 4 NA 3 0.53 102/102 29 3 NA 3 0.09 102/92 30 3 NA 2 0.15 99I0I 31 3 NA 2 o.13 93/55 32 3 NA 2 0.17 103/103 33 6 NA 7 0.68 i2/103 34 3 NA 6 0.37 100/101 35 2 NA 3 0.19 100/1 36 6 NA 8 0.34 69/89 37 5 NA 2 0.34 68/85 38V NA 2 0 38 61/92 39 5 NA 9 0 19 51/75 40 6 NA 908 97/Io 41 5 NA 16 0 12 '93'92 42 4 NA 14 0 979 43 4 NA 2 014 :97/97 -5NA 2 0.16 9797 45 NA 2 0.08 97/98 46 4 NA 2 0.12 99/98 47 3 NA 2 020 9696 48 2 NA 2 0.09 101/12 49 2 NA 2 0.10 1011/19 4 Example Disintegration Oral In-vitro DT Tensile Dissolution No test in petri dissolving (see) strength (5 / 15 dish (see) time (see) (N/mm 2 ) minutes) %i) 50 32 30 196 0.80 NA 51 150 39 124 0.97 NA 52 35 51 128 0.27 NA 53 > 300 0 > 30 minutes <.005 NA 54 00 >30 minutes 0 05 NA 55 2 5 22 40 005 NA 56 36 30 20 <0.05 NA 58 2 5 <2 <00 5 NA 592 <2 0.15 NA 60 24 <2 0.06 NA NA - Not Applicable for column 3 as the oral dissolving time was measured for placebo lyophilisates only. NA - Not applicable for column 6 as the dissolution time was measured for lyophilisate containing drug substances only. S. Pharmacokinetic test A comparative test was carried out to evaluate the pharmacokinetic profile of the composition of Example 26 (240 pg desmopressin acetate, levan and mannitol) (the test composition) with a reference composition comprising 240 pg desmopressin acetate. fish gelatin and mannitol (Minirin Melt®). The test was carried out in parallel design by single sublingual administration of the respective compositions to eight New Zealand rabbits in each treatment group. Blood samples were taken at specified time intervals from each treatment group and analyzed for Desropressin content. The pharmacokinetic parameters were calculated for individual rabbits using non compartmental analysis. The rate and extent of absorption of Desmopressin were similar in test and reference compositions, and the test by reference ratio of Cmax (peak or maximum concentration) and AUCI, (Area Under Curve computed up to 44 H:\rec\Itenvoven\NRPoI\DCC\REC\583527 DOC-2/I/20B last sampling time) were within 20% of reference composition. Further, Cm, for the test composition was higher in comparison to the reference composition. Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forns part of the common general knowledge in the field of endeavour to which this specification relates. - 45-

Claims (23)

1. A pharmaceutical composition comprising: (a) at least one matrix-forming agent that is levan to form an open matrix network; and (b) at least one pharmaceutically active ingredient chosen from desmopressin and desmopressin acetate, carried by the open matrix network, wherein at least 80% of the composition dissolves within 30 seconds upon contact with an aqueous solution or with saliva, and the composition is an orodispersible pharmaceutical dosage form.

2. The pharmaceutical composition according to claim 1, further comprising one or more secondary matrix-forming agents.

3. The pharmaceutical composition according to claim 2, wherein the one or more secondary matrix forming agent is selected from the group consisting of trehalose, raffinose and mannitol.

4. The pharmaceutical composition according to claim 2 or 3, wherein the one or more secondary matrix forming agent is mannitol.

5. The pharmaceutical composition according to any one of claims 1 to 4, wherein the at least one pharmaceutically active ingredient is desmopressin.

6. The pharmaceutical composition according to any one of claims 1 to 4, wherein the at least one pharmaceutically active ingredient is desmopressin acetate.

7. The pharmaceutical composition according to any one of claims 1 to 6, wherein the 2 composition has a tensile strength from about 0.05-1.6 N/mm

8. The pharmaceutical composition according to any one of claims 1 to 7, wherein at least 80% of the composition dissolves within 10 seconds upon contact with the aqueous solution. - 46 - H:\rec\Interwoven\NRPortbl\DCC\REC\8327007 Ldocx-1/09/2015

9. The pharmaceutical composition according to any one of claims 1 to 7, wherein at least 80% of the composition dissolves within 10 seconds upon contact with the saliva.

10. A pharmaceutical composition prepared by a process comprising at least a step of sublimating a solvent from a liquid preparation that comprises: (a) at least one matrix forming agent that is levan; and (b) at least one pharmaceutically active ingredient chosen from desmopressin and desmopressin acetate, wherein at least 80% of the composition dissolves within 30 seconds upon contact with an aqueous solution or with saliva, and the composition is an orodispersible pharmaceutical dosage form.

11. The pharmaceutical composition according to claim 10, wherein the at least one pharmaceutically active ingredient is desmopressin.

12. The pharmaceutical composition according to claim 10, wherein the at least one pharmaceutically active ingredient is desmopressin acetate.

13. The pharmaceutical composition according to claim 10, wherein the liquid preparation further comprises one or more secondary matrix-forming agents.

14. The pharmaceutical composition according to claim 13, wherein the one or more secondary matrix-forming agent is mannitol.

15. A pharmaceutical composition comprising: (a) at least one matrix-forming agent that is levan to form an open matrix network; and (b) desmopressin carried by the open matrix network, wherein at least 80% of the composition dissolves within 30 seconds upon contact with an aqueous solution or with saliva, and the composition is an orodispersible pharmaceutical dosage form.

16. The pharmaceutical composition according to claim 15, further comprising a secondary matrix forming agent that is mannitol. - 47 - H:\rec\Interwoven\NRPortbl\DCC\REC\8327007 Ldocx-1/09/2015

17. A blister pack having one or more depressions disposed therein, wherein each of the one or more depressions comprises a pharmaceutical composition, the composition comprising: (a) at least one matrix-forming agent that is levan to form an open matrix network; and (b) at least one pharmaceutically active ingredient chosen from desmopressin and desmopressin acetate carried by the open matrix network, wherein at least 80% of the tablet dissolves within 30 seconds upon contact with an aqueous solution or with saliva, and the composition is an orodispersible pharmaceutical dosage form.

18. The blister pack according to claim 17, which is prepared by a process comprising steps of: (a) introducing a liquid preparation into one or more depressions of a blister pack, the liquid preparation comprising the matrix forming agent and the pharmaceutically active ingredient; and (b) sublimating the solvent from the liquid preparation in the one or more depressions.

19. The blister pack according to claim 17 or 18, wherein the composition further comprises one or more secondary matrix-forming agents.

20. The blister pack according to claim 19, wherein the one or more secondary matrix forming agents is selected from the group consisting of trehalose, raffinose, and mannitol.

21. The blister pack according to claim 20, wherein the one or more secondary matrix forming agent is mannitol.

22. The blister pack according to any one of claims 17 to 21, wherein the at least one pharmaceutically active ingredient is desmopressin.

23. The blister pack according to any one of claims 17 to 21, wherein the at least one pharmaceutically active ingredient is desmopressin acetate. - 48 -