Pharmaceutical formulation, its use and its preparation process, as well as solid dosage form

Description

[001] The present invention relates to pharmaceutical formulations comprising an active pharmaceutical ingredient; and a copolymer of methacrylic acid, hydroxypropyl methylcellulose or a combination thereof, and solid dosage forms comprising said pharmaceutical formulations. The invention also relates to processes for preparing such pharmaceutical formulations and to the use of such pharmaceutical formulations for the prevention or treatment of a disease, syndrome, condition or disorder. BACKGROUND OF THE INVENTION

[002] Flaviviruses, which are transmitted by mosquitoes or ticks, cause potentially lethal infections in humans, such as encephalitis and hemorrhagic fever. Four distinct but closely related serotypes of dengue virus (Flavivirus dengue) are known. Document WO 2016 / 180696 discloses active pharmaceutical agents that show high potent activity against all four (4) serotypes of dengue virus.

[003] Many active pharmaceutical ingredients (APIs) have properties such as hydrophobicity and instability, leading to challenges in providing suitable pharmaceutical formulations.

[004] There is a need for improved pharmaceutical formulations of active pharmaceutical ingredients, such as the dengue viral replication inhibitors described in WO 2016 / 180696. SUMMARY OF THE INVENTION

[005] The present invention relates to a formulation Petition 870260061215, dated 06 / 22 / 2026, page 10 / 245 2 / 105 pharmaceutical company comprising:

[006] a) an active pharmaceutical ingredient (API); and

[007] b1) methacrylic acid copolymer, or

[008] b2) a cellulose derivative such as methyl cellulose (MC), ethyl cellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethylcellulose (CMC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC);

[009] where API is a dengue viral replication inhibitor.

[0010] The embodiments of the invention include a pharmaceutical formulation, as described herein, in which the API is a dengue viral replication inhibitor.

[0011] The invention also provides a solid dosage form comprising a pharmaceutical formulation, as described herein.

[0012] In embodiments in which the API is a dengue viral replication inhibitor, the invention provides methods for treating or preventing a disease, syndrome, condition or disorder in an individual, including a mammal and / or human being in which the disease, syndrome, condition or disorder is a dengue viral infection, using pharmaceutical formulations and solid dosage forms described herein.

[0013] In certain embodiments, the invention is directed to the method for inhibiting dengue viral replication in a mammal and / or human being infected with dengue virus or at risk of being infected with dengue virus.

[0014] The present invention is also directed to the use of such pharmaceutical formulations and / or solid dosage in the preparation of a medicament, wherein the medicament is prepared to treat or prevent dengue viral infections.

[0015] The present invention is further directed to such pharmaceutical formulations and / or solid dosage forms for use as a medicament. Petition 870260061215, dated 06 / 22 / 2026, page 11 / 245 3 / 105 In another embodiment, the present invention is directed to pharmaceutical formulations and / or solid dosage forms described herein for use in the treatment or prevention of dengue viral infections.

[0016] In certain embodiments, the present invention is directed to pharmaceutical formulations and / or solid dosage forms described herein for use in inhibiting dengue viral replication in a mammal and / or human being.

[0017] The invention also provides a process for preparing a solid dosage form as described herein, wherein the process comprises the steps of:

[0018] a) dissolve the API in a solvent to form a solution;

[0019] b) mix the methacrylic acid or hydroxypropyl methylcellulose copolymer or a combination thereof with the solution formed in step a), thus obtaining a mixture;

[0020] c) spray dry the mixture to obtain a solid dispersion;

[0021] d) optionally, mix the solid dispersion with at least one pharmaceutically acceptable excipient;

[0022] provide a pharmaceutical formulation, as described herein.

[0023] The invention also provides a process for preparing a solid dosage form described herein, wherein the process comprises the steps of:

[0024] a) dissolve the API in a solvent to form a solution;

[0025] b) mix the methacrylic acid or hydroxypropyl methylcellulose copolymer or a combination thereof with the solution formed in step a), thus obtaining a mixture;

[0026] c) spray dry the mixture to obtain a solid dispersion;

[0027] d) optionally, mix the solid dispersion with at Petition 870260061215, dated 06 / 22 / 2026, page 12 / 245 4 / 105 minus one pharmaceutically acceptable excipient;

[0028] e) compress the mixture into a tablet;

[0029] to provide a solid dosage form as described herein.

[0030] In certain embodiments, the invention provides a process for preparing a pharmaceutical formulation or a solid dosage form, as described herein, wherein the process comprises combining the active pharmaceutical ingredient with a methacrylic acid copolymer or a cellulose derivative (e.g., hydroxypropyl methylcellulose) to form the pharmaceutical formulation or the solid dosage form. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] The summary, as well as the detailed description below, are further understood when read in conjunction with the accompanying drawings. For the purpose of illustrating the invention, exemplary embodiments of the invention are shown in the drawings; however, the invention is not limited to the specific description in the drawings.

[0032] Figure 1 is a graph of the percentage (%) of API dissolved as a function of incubation time for solid dispersions of concepts 1 to 7, prepared in Example 1. The graph shows a 2-phase dissolution profile in simulated gastric fluid (SGF) and simulated intestinal fluid in a fasting state (FaSSIF).

[0033] Figure 2 is a graph of the % of API dissolved as a function of incubation time for solid dispersions of concepts 8 to 12, prepared in Example 1. The graph shows a 2-phase dissolution profile in simulated gastric fluid (SGF) and simulated fasting state intestinal fluid (FaSSIF).

[0034] Figures 3A and 3B are graphs of the % of dissolved API as a function of incubation time (Figure 3A) and the weight (in mg) of dissolved API as a function of incubation time (Figure 3B) for Petition 870260061215, dated 06 / 22 / 2026, page 13 / 245 5 / 105 solid dispersions prepared in Example 5B. The graphs show a 2-phase dissolution profile in simulated gastric fluid (SGF - to the left of the vertical dashed line) and simulated intestinal fluid in a fasting state (FaSSIF - to the right of the vertical dashed line).

[0035] Figure 4 is a graph of the % of API dissolved as a function of incubation time for solid dispersions prepared in Example 5B. The graph shows a 2-phase dissolution profile in simulated gastric fluid (SGF - to the left of the vertical dashed line) and simulated fed-state intestinal fluid (FeSSIF - to the right of the vertical dashed line). DETAILED DESCRIPTION OF THE INVENTION

[0036] The description can be understood more fully by reference to the description presented below, including the following glossary of terms and the examples in the conclusion. It should be considered that certain features of the disclosed pharmaceutical formulations and methods which are, for clarity, described here in the context of separate aspects, may also be provided together in a single aspect. Conversely, several features of disclosed pharmaceutical formulations and methods which are, for brevity, described in the context of a single aspect, may also be provided separately or in any subcombination.

[0037] Some of the quantitative expressions presented here are not qualified with the term about. It should be understood that when the term about is used, explicitly or not, any and all quantities presented here refer to the actual value given and also to the approximation of that given value that would reasonably be inferred based on the technique, including approximations due to experimental and / or measurement conditions for that given value. The terms about or approximately, as used here, when referring to a numerical value or range, allow a Petition 870260061215, dated 06 / 22 / 2026, p. 14 / 245 6 / 105 degree of variability in the value or range, for example, within 10% (i.e., ±10%), within 5% (i.e., ±5%), or within 2.5% (i.e., ±2.5%) of a stated value or a stated limit of a range.

[0038] Throughout the description and claims of this descriptive report, the words includes and contains, as well as variations of those words, for example, including and comprise, mean including, but not limited to, and are not intended to exclude (and do not exclude) other components.

[0039] The citation of numerical ranges with extremes includes all whole numbers and, where appropriate, the fractions comprised within that range (for example, a range from 1 to 5 may include 1, 2, 3, 4 when referring, for example, to a number of elements, and may also include 1.5, 2, 2.75 and 3.80 when referring, for example, to measurements). The citation of extremes also includes the extreme values ​​themselves (for example, from 1.0 to 5.0 includes both 1.0 and 5.0). Any numerical range mentioned here is intended to include all subranges included within the numerical range.

[0040] All references mentioned in this descriptive report are incorporated herein by reference in their entirety. In particular, the teachings of all references specifically mentioned herein are incorporated by reference.

[0041] The reference, throughout this descriptive report, to an embodiment means that a specific feature, structure, or characteristic described in relation to an embodiment is included in at least one embodiment of the present invention. Thus, the occurrence of expressions of the type "in an embodiment," being an article or a numeral, in various places throughout this descriptive report does not necessarily refer to the same embodiment, but this is possible. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner, as would be evident from a Petition 870260061215, dated 06 / 22 / 2026, page 15 / 245 7 / 105 skilled in the art from this description, in one or more embodiments. Furthermore, although some embodiments described herein include some, but not other, features included in other embodiments, combinations of features from different embodiments are intended to be within the scope of the invention, and form different embodiments, as would be understood by those skilled in the art.

[0042] For use in medicines, cocrystals or salts of the API, such as salts of compounds of Formula (I), as disclosed herein, refer to pharmaceutically acceptable nontoxic salts. Pharmaceutically acceptable may mean approved or eligible for approval by a federal or state government regulatory agency or equivalent agency in countries other than the United States or that is mentioned in the United States Pharmacopeia, or another generally recognized pharmacopoeia for use in animals and, more particularly, in humans.

[0043] However, other salts may be useful in the preparation of the API, such as compounds of Formula (I) or their pharmaceutically acceptable salt forms. Suitable pharmaceutically acceptable salts of the API such as compounds of Formula (I) include acid addition salts which may, for example, be formed by mixing a solution of the compound with a solution of a pharmaceutically acceptable acid such as hydrochloric acid, sulfuric acid, fumaric acid, maleic acid, succinic acid, acetic acid, benzoic acid, citric acid, tartaric acid, carbonic acid or phosphoric acid. In addition, when the API such as compounds of Formula (I) carries an acid moiety, their suitable pharmaceutically acceptable salts may include alkali metal salts such as sodium or potassium salts; alkaline earth metal salts such as calcium or magnesium salts; and salts formed with suitable organic ligands such as quaternary ammonium salts.Thus, representative pharmaceutically acceptable salts. Petition 870260061215, dated 06 / 22 / 2026, page 16 / 245 8 / 105 include acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, estolate, esilate, fumarate, gluceptate, gluconate, glutamate, glycolyllarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, ammonium salt N-methylglucamine, oleate, pamoate (embonate), palmitate, pantothenate, phosphate / diphosphate, polygalacturonate, silicylate, stearate, sulfate, subacetate, succinate, tannate, tartrate, theoclate, tosylate, triethiodide and valerate.

[0044] Representative acids and bases that can be used in the preparation of pharmaceutically acceptable salts include acids including acetic acid, 2,2-dichloroacetic acid, acylated amino acids, adipic acid, alginic acid, ascorbic acid, L-aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, (+)-camphoric acid, camphorsulfonic acid, (+)-(1S)-camphor-10sulfonic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, D-gluconic acid, D-glucuronic acid, L-glutamic acid, acid α-oxoglutaric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, (+)-L-lactic acid, (±)-DL-lactic acid, lactobionic acid, maleic acid, (-)-L-malic acid, malonic acid, (±)-DLmandelic acid,methanesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phosphoric acid, L-pyroglutamic acid, salicylic acid, 4-aminosalicylic acid, sebaic acid, stearic acid, succinic acid, Petition 870260061215, dated 06 / 22 / 2026, page 17 / 245 9 / 105 sulfuric acid, tannic acid, (+)-L-tartaric acid, thiocyanic acid, p-toluenesulfonic acid and undecylenic acid; and bases including ammonia, larginine, benetamine, benzathine, calcium hydroxide, choline, deanol, diethanolamine, diethylamine, 2-(diethylamino)-ethanol, ethanolamine, ethylenediamine, N-methyl-glucamine, hydrabamino, 1H-imidazole, L-lysine, magnesium hydroxide, 4-(2-hydroxyethyl)-morpholine, piperazine, potassium hydroxide, 1-(2-hydroxyethyl)-pyrrolidine, sodium hydroxide, triethanolamine, tromethamine and zinc hydroxide.

[0045] If the API such as the compounds of Formula (I) have at least one chiral center, they may consequently exist as enantiomers. When the compounds have two or more chiral centers, they must additionally exist as diastereomers. It should be understood that all such isomers and mixtures thereof are encompassed within the scope of the present invention. Furthermore, some of the compounds may exist as polymorphs and, as such, are included in the present invention. In addition, some of the compounds may form solvates with water (i.e., hydrates) or organic solvents, and such solvates are also within the scope of this invention. Those skilled in the art will understand that the term compound for use in the present invention shall include the solvated compounds of Formula (I).

[0046] When the processes for preparing APIs such as the compounds of Formula (I) give rise to a mixture of stereoisomers, these isomers can be separated by conventional techniques such as preparative chromatography. The compounds can be prepared in racemic form, or the individual enantiomers can be prepared by enantiospecific synthesis or by resolution. The compounds can, for example, be separated into their component enantiomers by standard techniques such as the formation of diastereomeric pairs by salt formation with an optically active acid such as (-)-di-p-toluoyl-d-acid. Petition 870260061215, dated 06 / 22 / 2026, page 18 / 245 10 / 105 tartaric and / or (+)-di-p-toluoyl-l-tartaric acid followed by fractional crystallization and regeneration of the free base. The compounds can also be resolved by forming diastereomeric esters or amides, followed by chromatographic separation and removal of the chiral auxiliary. Alternatively, the compounds can be separated using a chiral stationary phase or isochiral column.

[0047] In one embodiment of the pharmaceutical formulation of the present invention, the API (for example, a compound of Formula (I) comprising, consists of and / or essentially consists of the (+)-enantiomer, said compound being substantially free of the (-)-isomer. In the present context, substantially free means less than about 25% by weight, preferably less than about 10% by weight, more preferably less than about 5% by weight, even more preferably less than about 2% by weight and even more preferably less than about 1% by weight of the (-)-isomer calculated as follows: % of (+) — enantiomer (mass (+) — enantiomer) (mass (+) — enantiomer) + (mass (-) — enantiomer) x 100.

[0048] In another embodiment of the pharmaceutical formulation of the present invention, the API is a compound of Formula (I) comprising, consisting of, and essentially consisting of the (-)-enantiomer, said compound being substantially free of the (+)-isomer. In the present context, substantially free of means less than about 25% by weight, preferably less than about 10% by weight, more preferably less than about 5% by weight, even more preferably less than about 2% by weight, and even more preferably less than about 1% by weight of the (+)-isomer calculated as follows: Petition 870260061215, dated 06 / 22 / 2026, page 19 / 245 11 / 105 % of (—) — enantiomer (mass (—) — enantiomer) (mass (+) — enantiomer) + (mass (—) — enantiomer) x 100.

[0049] During any of the compound preparation processes of the various embodiments of the present invention, it may be necessary and / or desirable to protect the sensitive or reactive groups in any of the related molecules. This can be accomplished by means of conventional protecting groups, such as those described in Protective Groups in Organic Chemistry, Second Edition, J.F.W. McOmie, Plenum Press, 1973; T.W. Greene & P.G.M. Wuts, Protective Groups in Organic Synthesis, John Wiley & Sons, 1991; and T.W. Greene & P.G.M. Wuts, Protective Groups in Organic Synthesis, Third Edition, John Wiley & Sons, 1999. The protecting groups can be removed at a convenient subsequent stage using methods known in the art.

[0050] Unless otherwise indicated, the terms % by weight and percentage by weight are used interchangeably to refer to the concentration of an ingredient (e.g., excipient or active pharmaceutical ingredient) relative to the weight of the pharmaceutical formulation.

[0051] The term ambient temperature (TA) refers to a temperature of about 15°C to about 30°C, in particular, about 20°C to about 30°C. Preferably, ambient temperature is a temperature of about 25°C.

[0052] An average molecular weight can, for example, refer to a numerical average or a weight-average molecular weight. The average molecular weight can, for example, be measured using gel permeation chromatography or mass spectrometry.

[0053] The term individual refers to an animal, preferably a mammal, with the highest preference a human being, that has been the Petition 870260061215, dated 06 / 22 / 2026, p. 20 / 245 12 / 105 object of treatment, observation or experiment.

[0054] The terms active compound, active ingredient and active pharmaceutical ingredient are used interchangeably herein.

[0055] The term therapeutically effective amount refers to an amount of an active compound or pharmaceutical agent that produces the biological or medicinal response in a tissue system, animal or human, that is being sought by a researcher, veterinarian, physician or other clinician, including the reduction or inhibition of an enzyme or protein activity, or improvement of symptoms, relief of conditions, slowing or delaying of disease progression, or prevention of a disease.

[0056] In embodiments in which the API is a dengue viral replication inhibitor, the term therapeutically effective amount may refer to the amount of a formulation of the present invention that, when administered to an individual, is effective in at least partially alleviating, inhibiting, preventing and / or improving a condition, disorder or disease caused by a dengue virus in said individual.

[0057] As used herein, the term dengue virus refers to the positive-sense single-stranded RNA virus of the family Flaviviridae; four distinct but closely related serotypes of dengue virus are known, namely DENV-1, DENV-2, DENV-3, and DENV-4. Viruses of the genus Flavivirus, which are transmitted by mosquitoes or ticks, cause potentially lethal infections in humans, such as encephalitis and hemorrhagic fever.

[0058] As used herein, the term dengue viral replication inhibitor refers to an agent that inhibits or reduces at least one condition, symptom, disorder and / or disease caused by a dengue virus. Petition 870260061215, dated 06 / 22 / 2026, page 21 / 245 13 / 105

[0059] As used herein, except where otherwise specified, the term affect or affected (when referring to a disease, syndrome, condition or disorder that is affected by the inhibition of dengue virus replication) includes a reduction in the frequency and / or severity of one or more symptoms or manifestations of said disease, syndrome, condition or disorder; and / or includes the prevention of the development of one or more symptoms or manifestations of said disease, syndrome, condition or disorder or the development of the disease, condition, syndrome or disorder.

[0060] As used herein, the term treat or treatment of any disease, condition, syndrome, or disorder refers, in one modality, to attenuating the disease, condition, syndrome, or disorder (i.e., halting or reducing the development of the disease or at least one of the clinical symptoms of the disease). In another modality, treat or treatment refers to attenuating or improving at least one physical parameter, including those that may not be discernible to the individual. In a further modality, treat or treatment refers to modulating the disease, condition, syndrome, or disorder, either physically (e.g., stabilizing a discernible symptom), physiologically (e.g., stabilizing a physical parameter), or both. In yet another modality, treat or treatment refers to preventing or delaying the onset or development or progression of the disease, condition, syndrome, or disorder.

[0061] As used herein, the terms avoid, prevent and prevention refer to reducing the risk of acquiring or developing a particular condition, disease or symptoms of disease, or to reducing or inhibiting the recurrence of said condition, disease or symptoms of disease in an individual who is not ill but is at risk of becoming ill. For example, said individual is or has been in a high-risk area or has been or may be near a person with the disease. Petition 870260061215, dated 06 / 22 / 2026, p. 22 / 245 14 / 105

[0062] As used herein, an excipient is an inactive ingredient in a pharmaceutical formulation. Examples of excipients include diluents, wetting agents (e.g., surfactants), binders, flow agents, lubricants, disintegrants, and the like.

[0063] As used herein, a disintegrating or disintegrating agent is an excipient that hydrates a pharmaceutical formulation and aids in tablet dispersion. Examples of disintegrating agents include croscarmellose sodium, crospovidone (i.e., cross-linked polyvinyl N-pyrrolidone), sodium starch glycolate, or any combination thereof.

[0064] As used herein, a diluent or filler is an excipient that adds volume to a pharmaceutical formulation. Examples of diluents include lactose, sorbitol, celluloses, calcium phosphates, starches, sugars (e.g., mannitol, sucrose, or similar) or any combination thereof.

[0065] As used herein, a wetting agent or surfactant is an excipient that imparts enhanced solubility and / or wettability to pharmaceutical formulations. Examples of wetting agents include sodium lauryl sulfate (SLS), sodium stearyl fumarate (SSF), polyoxyethylene sorbitan monooleate 20 (i.e., polysorbate 20) (e.g., Tween™ or Tween 20), Soluplus®, or any combination thereof.

[0066] As used herein, a binder is an excipient that imparts enhanced cohesion or tensile strength (e.g., hardness) to a pharmaceutical formulation. Examples of binders include dibasic calcium phosphate, sucrose, corn starch (maize starch), microcrystalline cellulose, and modified cellulose (e.g., hydroxymethyl cellulose).

[0067] As used herein, a flow agent is an excipient that imparts flow properties to the pharmaceutical formulation. Petition 870260061215, dated 06 / 22 / 2026, page 23 / 245 15 / 105 improved. Examples of flow agents include colloidal silica and / or talc.

[0068] As used herein, a colorant is an excipient that imparts a desired color to a pharmaceutical formulation. Examples of colorants include commercially available pigments such as FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2, other FD&C Blue colors, titanium dioxide, iron oxide, and / or combinations thereof. Other colorants include commercially available pigments such as FD&C Green No. 3.

[0069] As used herein, a lubricant is an excipient that is added to the pharmaceutical formulation and that is pressed into tablets. The lubricant assists in the compaction of granules into tablets and the ejection of a tablet from a pharmaceutical formulation from a die press. Examples of lubricants include magnesium stearate, stearic acid (stearin), hydrogenated oil, sodium stearyl fumarate, or any combination thereof.

[0070] The preferred statements (characteristics) and embodiments of the pharmaceutical formulations, uses, and process of this invention are defined below. Each statement and embodiment of the invention thus defined may be combined with any other statement and / or embodiment, unless clearly indicated otherwise. In particular, any feature / characteristic indicated as being preferred or advantageous may be combined with any other features / characteristics or statements indicated as being preferred or advantageous. So far, the present invention is, in particular, characterized by any one or any combination of one or more of the aspects and embodiments listed below, with any other statement and / or embodiment.

[0071] 1. Pharmaceutical formulation comprising: Petition 870260061215, dated 06 / 22 / 2026, page 24 / 245 16 / 105

[0072] a) an active pharmaceutical ingredient (API); and

[0073] b1) methacrylic acid copolymer, or

[0074] b2) a cellulose derivative such as methyl cellulose (MC), ethyl cellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) or a combination thereof. Preferably, the cellulose derivative is HPMC.

[0075] wherein the API is a dengue viral replication inhibitor.

[0076] 2. Pharmaceutical formulation, according to statement 1, wherein the pharmaceutical formulation is a solid formulation.

[0077] 3. Pharmaceutical formulation, according to either of statements 1 or 2, wherein the API and the methacrylic acid copolymer are present in said formulation in a ratio of 4:1 w / w 1:9 w / w, preferably 3.9:1 w / w 1:8 w / w; preferably 3.8:1 w / w 1:7 w / w; 3.7:1 w / w 1:6 w / w; preferably 3.6:1 w / w 1:5 w / w, preferably 3.5:1 w / w 1:4.5 w / w; preferably 3.1 w / w 1:4 w / w; preferably 2.5:1 w / w 1:3.5 w / w; preferably 2.1 w / w 1:3 w / w; preferably 2.5:1 p / pa 1:2.5 p / p, preferably 2:1 p / pa 1:2 p / p; preferably 1.5:1 p / pa 1:1.5 p / p or a ratio comprised within any two ratios mentioned herein, or a range or subrange of ratios within any two ratios mentioned herein.

[0078] 4. Pharmaceutical formulation, according to any of statements 1 or 2, wherein the API and the cellulose derivative (e.g., hydroxypropyl methylcellulose) are present in said formulation in a ratio of 4:1 w / w 1:5 w / w, preferably 3.5:1 w / w 1:4.5 w / w; preferably 3:1 w / w 1:4 w / w; preferably 2.5:1 w / w 1:3.5 w / w; preferably 2:1 w / w 1:3 w / w; preferably 2.5:1 w / w 1:2.5 w / w, preferably 2:1 w / w 1:2 w / w; preferably 1.5:1 w / w 1:1.5 w / w or a ratio comprised within any Petition 870260061215, dated 06 / 22 / 2026, p. 25 / 245 17 / 105 two ratios mentioned here, or a ratio range or sub-range within any two ratios mentioned here.

[0079] 5. Pharmaceutical formulation, according to any of statements 1 to 4, wherein the methacrylic acid copolymer is a copolymer / ester of acrylic and / or methacrylic acids such as the compounds sold under the trade name Eudragit® including, but not limited to, Eudragit® L-100, Eudragit® E-100, Eudragit® L-100-55 or any mixtures thereof.

[0080] 6. Pharmaceutical formulation, according to any one of statements 1 to 5, wherein the methacrylic acid copolymer is selected from the group comprising a methacrylic acid and methyl methacrylate copolymer; a methacrylic acid and ethyl acrylate copolymer; and mixtures thereof.

[0081] 7. Pharmaceutical formulation, according to any one of statements 1 to 6, wherein the methacrylic acid copolymer is a copolymer of methacrylic acid and methyl methacrylate.

[0082] 8. Pharmaceutical formulation, according to statement 7, wherein the molar ratio between methacrylic acid and methyl methacrylate in the copolymer is 0.5:2 to 0.6:1.5, preferably 0.8:1.3 to 1.2:1, more preferably around 1:1.

[0083] 9. Pharmaceutical formulation, according to any one of statements 1 to 8, wherein the methacrylic acid copolymer is poly(methacrylic acid-co-methyl methacrylate) 1:1 (EUDRAGIT® L100).

[0084] 10. Pharmaceutical formulation, according to any one of statements 1 to 9, wherein the cellulose derivative is hydroxypropyl methylcellulose having a viscosity ranging from 3 to 5,000 mPa.s in a 2% by weight solution in H2O at 25 °C, such as HPMC E5, HPMC E6, HPMC E15, HPMC E50, HPMC K3, HPMC K4M, HPMC-AS and mixtures thereof.

[0085] 11. Pharmaceutical formulation, according to any one Petition 870260061215, dated 06 / 22 / 2026, page 26 / 245 18 / 105 of statements 1 to 10, wherein the cellulose derivative is hydroxypropyl methylcellulose having a viscosity ranging between 3 and 500 mPa.s in a 2% by weight solution in H2O at 25 °C as HPMC E5, HPMC E6, HPMC E15, HPMC E50 and mixtures thereof.

[0086] 12. Pharmaceutical formulation, according to any one of statements 1 to 11, wherein the cellulose derivative has a viscosity ranging from 3 to 50 mPa.s in a 2% by weight solution in H2O at 25 °C. Preferably, said cellulose derivative is hydroxypropyl methylcellulose selected from HPMC E5, HPMC E6, HPMC E15, HPMC E50 and mixtures thereof.

[0087] 13. Pharmaceutical formulation, according to any of statements 1 to 12, wherein the formulation comprises a maximum of 50% by weight, preferably a maximum of 40% by weight, more preferably a maximum of 30% by weight, most preferably a maximum of 25% by weight, and even more preferably 20% by weight of the API in relation to the total weight of the formulation.

[0088] 14. Pharmaceutical formulation, according to any of statements 1 to 13, wherein the formulation comprises from 0.1% by weight to 50% by weight, preferably from 1% by weight to 40% by weight, more preferably from 2.5% by weight to 30% by weight, most preferably from 5% by weight to 25% by weight of the API in relation to the total weight of the formulation.

[0089] 15. Pharmaceutical formulation, according to any one of statements 1 to 14, wherein the formulation additionally comprises one or more pharmaceutically acceptable excipients selected from disintegrants, binders, diluents, lubricants, stabilizers, wetting agents, flow agents, osmotic agents, colorants, plasticizers and coatings.

[0090] 16. Pharmaceutical composition, according to any one of statements 1 to 15, wherein the formulation comprises Petition 870260061215, dated 06 / 22 / 2026, page 27 / 245 19 / 105 additionally one or more excipients; wherein the formulation comprises a maximum of 80% by weight, preferably a maximum of 70% by weight, preferably a maximum of 60% by weight of one or more excipients in relation to the total weight of the formulation; and / or wherein the formulation comprises at least 10% by weight, preferably at least 20% by weight, preferably at least 30% by weight of one or more excipients in relation to the total weight of the formulation.

[0091] 17. Pharmaceutical formulation, according to any of statements 1 to 16, wherein the formulation additionally comprises one or more diluents; wherein the formulation comprises a maximum of 95% by weight, preferably a maximum of 80% by weight, preferably a maximum of 75% by weight of diluent in relation to the total weight of the formulation; and / or wherein the formulation comprises at least 5% by weight, preferably at least 10% by weight, preferably at least 15% by weight of diluent in relation to the total weight of the formulation.

[0092] 18. Pharmaceutical formulation, according to any of statements 1 to 17, wherein the formulation additionally comprises one or more disintegrants; wherein the formulation comprises a maximum of 30% by weight, preferably a maximum of 20% by weight, preferably a maximum of 15% by weight, preferably a maximum of 10% by weight of the disintegrant in relation to the total weight of the formulation; and / or wherein the formulation comprises at least 1% by weight, preferably at least 2.5% by weight, preferably at least 5% by weight, preferably at least 8% by weight of the disintegrant in relation to the total weight of the formulation.

[0093] 19. Pharmaceutical formulation, according to any of statements 1 to 18, wherein the formulation additionally comprises one or more binders; wherein the formulation comprises a maximum of 50% by weight, preferably a maximum of 45% Petition 870260061215, dated 06 / 22 / 2026, page 28 / 245 20 / 105 by weight, preferably a maximum of 40% by weight, more preferably a maximum of 35% by weight of the binder in relation to the total weight of the formulation; and / or wherein the formulation comprises at least 5% by weight, preferably at least 10% by weight, preferably at least 15% by weight, more preferably at least 20% by weight, with the maximum preference being 25% by weight of the binder in relation to the total weight of the formulation.

[0094] 20. Pharmaceutical formulation, according to any of statements 1 to 19, wherein the formulation additionally comprises one or more lubricants; wherein the formulation comprises a maximum of 5.5% by weight, preferably a maximum of 3.5% by weight, preferably a maximum of 2% by weight of the lubricant in relation to the total weight of the formulation; and / or wherein the formulation comprises at least 0.5% by weight, preferably at least 1% by weight, preferably at least 1.5% by weight of the lubricant in relation to the total weight of the formulation.

[0095] 21. Pharmaceutical formulation, according to any of statements 1 to 20, wherein the formulation additionally comprises one or more humectants; wherein the formulation comprises a maximum of 5.5% by weight, preferably a maximum of 3.5% by weight, preferably a maximum of 2% by weight of the humectant in relation to the total weight of the formulation; and / or wherein the formulation comprises at least 0.5% by weight, preferably at least 1% by weight, preferably at least 1.5% by weight of the humectant in relation to the total weight of the formulation.

[0096] 22. Pharmaceutical formulation, according to any one of statements 1 to 21, wherein the formulation additionally comprises one or more flow agents; wherein the formulation comprises a maximum of 10% by weight, preferably a maximum of 8% by weight, preferably a maximum of 5% by weight of the flow agent. Petition 870260061215, dated 06 / 22 / 2026, page 29 / 245 21 / 105 in relation to the total weight of the formulation; and / or wherein the formulation comprises at least 0.1% by weight, preferably at least 1% by weight, preferably at least 2% by weight of the flow agent in relation to the total weight of the formulation.

[0097] 23. Pharmaceutical formulation, according to any one of statements 1 to 22, wherein the formulation comprises a plurality of granules forming an intragranular phase of the formulation and one or more excipients forming an extragranular phase of the formulation.

[0098] 24. Pharmaceutical formulation, according to the declaration 23, wherein the formulation comprises at least 15% by weight; at least 20% by weight; at least 28% by weight; at least 34% by weight of the intragranular phase in relation to the weight of the pharmaceutical formulation.

[0099] 25. Pharmaceutical formulation, according to any of statements 23 or 24, wherein the formulation comprises at most 99% by weight, at most 93% by weight, at most 85% by weight, at most 80% by weight, at most 74% by weight; at most 73% by weight; at most 67% by weight; at most 63% by weight; at most 60% by weight, at most 53% by weight of the intragranular phase in relation to the weight of the pharmaceutical formulation.

[00100] 26. Pharmaceutical formulation, according to any one of statements 23 to 25, wherein the formulation comprises an intragranular phase and wherein the intragranular phase comprises from 1% by weight to 70% by weight; from 2% by weight to 60% by weight; from 3% by weight to 55% by weight; from 4% by weight to 50% by weight; from 5% by weight to 45% by weight; preferably from 5% by weight to 40% by weight; preferably from 10% by weight to 35% by weight; preferably from 15% by weight to 30% by weight of the API in relation to the total weight of the pharmaceutical formulation.

[00101] 27. Pharmaceutical formulation, according to any one of statements 23 to 26, wherein the formulation comprises a phase Petition 870260061215, dated 06 / 22 / 2026, page 30 / 245 22 / 105 intragranular, wherein the intragranular phase comprises from 5% to 60% by weight; preferably from 8% to 50% by weight; preferably from 15% to 45% by weight of methacrylic acid or hydroxypropyl methylcellulose copolymer or a mixture thereof in relation to the total weight of the pharmaceutical formulation.

[00102] 28. Pharmaceutical formulation, according to any one of statements 23 to 27, wherein the formulation comprises an intragranular phase and wherein the intragranular phase comprises from 5% by weight to 60% by weight; preferably from 10% by weight to 60% by weight; preferably from 10% by weight to 50% by weight; preferably from 15% by weight to 50% by weight of the filler in relation to the total weight of the pharmaceutical formulation.

[00103] 29. Pharmaceutical formulation, according to any one of statements 23 to 28, wherein the formulation comprises an intragranular phase comprising from 1% by weight to 10% by weight; preferably from 1% by weight to 9% by weight, preferably from 1.7% by weight to 8% by weight of the disintegrant in relation to the total weight of the pharmaceutical formulation.

[00104] 30. Pharmaceutical formulation, according to any one of statements 23 to 29, wherein the formulation comprises an intragranular phase comprising from 0.1% by weight to 5% by weight; preferably from 0.2% by weight to 4.7% by weight; preferably from 0.5% to 4.5% by weight of the flow agent in relation to the total weight of the pharmaceutical formulation.

[00105] 31. Pharmaceutical formulation, according to any one of statements 23 to 30, wherein the formulation comprises an intragranular phase comprising 0.1% by weight to 5% by weight; preferably 0.2% by weight to 4.7% by weight; preferably 0.5% to 4.5% by weight of the surfactant in relation to the total weight of the pharmaceutical formulation. Petition 870260061215, dated 06 / 22 / 2026, page 31 / 245 23 / 105

[00106] 32. Pharmaceutical formulation, according to any one of statements 23 to 31, wherein the formulation comprises an intragranular phase comprising from 0.1% by weight to 3% by weight; preferably from 0.2% by weight to 2.7% by weight; preferably from 0.5% to 2.5% by weight of the lubricant in relation to the total weight of the pharmaceutical formulation.

[00107] 33. Pharmaceutical formulation, according to any one of statements 23 to 32, wherein the formulation comprises an intragranular phase, wherein the intragranular phase comprises: (i) 5% to 45% by weight by weight; preferably 5% to 40% by weight by weight; preferably 10% to 35% by weight by weight; preferably 15% to 30% by weight of the API relative to the total weight of the pharmaceutical formulation; (ii) 5% to 60% by weight by weight; preferably 8% to 50% by weight by weight; preferably 15% to 45% by weight of methacrylic acid or hydroxypropyl methylcellulose copolymer or a mixture thereof relative to the total weight of the pharmaceutical formulation; (iii) 5% to 60% by weight by weight; preferably 10% to 60% by weight; preferably from 10% to 50% by weight; preferably from 15% to 50% by weight of the filler relative to the total weight of the pharmaceutical formulation; (iv) from 1% to 10% by weight;(v) 0.1% to 5% by weight; preferably 0.2% to 4.7% by weight; preferably 0.5% to 4.5% by weight of flow agent in relation to the total weight of the pharmaceutical formulation; (vi) 0.1% to 5% by weight; preferably 0.2% to 4.7% by weight; preferably 0.5% to 4.5% by weight of surfactant in relation to the total weight of the pharmaceutical formulation; and (vii) 0.1% to 3% by weight; preferably 0.2% to 2.7% by weight; preferably 0.5% to 2.5% by weight; Petition 870260061215, dated 06 / 22 / 2026, page 32 / 245 24 / 105 of the lubricant in relation to the total weight of the pharmaceutical formulation.

[00108] 34. Pharmaceutical formulation, according to any one of statements 23 to 33, wherein the pharmaceutical formulation comprises at least 5% by weight; at least 7% by weight; at least 10% by weight; at least 15% by weight; at least 20% by weight; at least 28% by weight; at least 34% by weight of the extragranular phase in relation to the total weight of the pharmaceutical formulation.

[00109] 35. Pharmaceutical formulation, according to any of statements 23 to 34, wherein the pharmaceutical formulation comprises a maximum of 74% by weight; a maximum of 73% by weight; a maximum of 67% by weight; a maximum of 63% by weight; a maximum of 53% by weight; a maximum of 40% by weight of the extragranular phase in relation to the total weight of the pharmaceutical formulation.

[00110] 36. Pharmaceutical formulation, according to any one of statements 23 to 35, wherein the formulation comprises an extragranular phase, wherein the extragranular phase comprises from 0.1% by weight to 5.0% by weight; preferably from 0.2% by weight to 4.7% by weight; preferably from 0.5% by weight to 3.5% by weight of the disintegrant in relation to the total weight of the pharmaceutical formulation.

[00111] 37. Pharmaceutical formulation, according to any one of statements 23 to 36, wherein the formulation comprises an extragranular phase, wherein the extragranular phase comprises from 0.1% by weight to 3% by weight; preferably from 0.2% by weight to 2.7% by weight; preferably from 0.5% by weight to 2.5% by weight of the lubricant in relation to the total weight of the pharmaceutical formulation.

[00112] 38. Pharmaceutical formulation, according to any one of statements 23 to 37, wherein the formulation comprises an extragranular phase, the extragranular phase comprising from 0.1% to 55% by weight; from 0.2% to 50% by weight; from 0.3% to 45% by weight; from 0.4% to 40% by weight; from 0.5% to Petition 870260061215, dated 06 / 22 / 2026, page 33 / 245 25 / 105 weight to 35% by weight; 0.6% by weight to 30% by weight; 0.7% by weight to 25% by weight; 0.8% by weight to 20% by weight; 1% by weight to 15% by weight; 1.3% by weight to 12% by weight; 2% by weight to 10% by weight; 2.5% by weight to 9% by weight; 3% by weight to 8% by weight; 4% by weight to 7% by weight; 5% by weight to 6% by weight of the load in relation to the total weight of the pharmaceutical formulation.

[00113] 39. Pharmaceutical formulation, according to any one of statements 23 to 38, wherein the formulation comprises an extragranular phase, wherein the extragranular phase comprises: (a) from 0.1% by weight to 5.0% by weight; preferably from 0.2% by weight to 4.7% by weight; preferably from 0.5% by weight to 3.5% by weight; more preferably from 1% by weight to 3% by weight of the disintegrator in relation to the total weight of the pharmaceutical formulation; (b) from 0.1% by weight to 3% by weight; preferably from 0.2% by weight to 2.7% by weight; preferably from 0.5% by weight to 2.5% by weight of the lubricant in relation to the total weight of the pharmaceutical formulation; and (c) from 1% by weight to 15% by weight, preferably from 1.3% by weight to 12% by weight; Preferably 2.5% to 8% by weight; more preferably 3 to 5% by weight of the filler relative to the total weight of the pharmaceutical formulation.

[00114] 40. Pharmaceutical formulation, according to any one of statements 1 to 39, wherein the API is a compound of Formula (I):

[00115] a stereoisomeric form, a salt, solvate or pharmaceutically acceptable polymorph thereof; said compound being Petition 870260061215, dated 06 / 22 / 2026, p. 34 / 245 26 / 105 selected from the group in which:

[00116] Ri is H, R2 is Fe R3 is H or CH3,

[00117] Ri is H, CH3or F, R2 is OCH3 and R3 is H, and

[00118] RiéH, R2is OCH3and R3is CH3.

[00119] R1 is CH3, R2 is Fe, R3 is H,

[00120] R1 is CF3 or OCF3, R2 is H and R3 is H,

[00121] R1 is OCF3, R2 is OCH3 and R3 is H, and

[00122] R1 is OCF3, R2 is H and R3 is CH3.

[00123] 41. Pharmaceutical formulation, according to the declaration 40, where the compound of Formula (I) is:

[00124] a stereoisomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof.

[00125] 42. Solid dosage form comprising the pharmaceutical formulation as defined in any of statements 1 to 41.

[00126] 43. Solid dosage form, according to the declaration 42, where the dosage form is an oral dosage form.

[00127] 44. Solid dosage form, according to statements 42 or 43, wherein the dosage form is a tablet.

[00128] 45. Solid dosage form, according to any of statements 42 to 44, wherein the formulation comprises 0.5 to 1,000 mg of the API; preferably 1 to 900 mg of the API; preferably 2 to 800 mg of the API; preferably 3 to 700 mg of the API; preferably 4 to 600 mg of the API; preferably 5 to 500 mg of the API; preferably 6 to 400 mg of the API; preferably 7 to 300 mg of the Petition 870260061215, dated 06 / 22 / 2026, p. 35 / 245 27 / 105 API; preferably 8 to 200 mg of API; preferably 9 to 100 mg of API; preferably 10 to 50 mg of API.

[00129] 46. Solid dosage form, according to any one of statements 42 to 45, wherein the formulation comprises at least 0.1 mg, at least 5 mg, at least 10 mg, at least 20 mg, at least 50 mg, at least 100 mg, at least 200 mg, at least 300 mg, at least 400 mg, at least 500 mg or at least 1,000 mg of the API; preferably the API is: MeO OvHou is a stereoisomeric form, a pharmaceutically acceptable salt, solvate, or polymorph thereof.

[00130] 47. Method of treating or preventing dengue viral infections, comprising administering to an individual in need a therapeutically effective amount of a pharmaceutical formulation as defined in any one of statements 1 to 41, or administering to an individual in need a therapeutically effective amount of the solid dosage form as defined in any one of statements 42 to 46.

[00131] 48. Use of a pharmaceutical formulation, in accordance with any of statements 1 to 41, for the preparation of a medicament to treat or prevent dengue viral infections.

[00132] 49. Use of a solid dosage form, according to any of statements 42 to 46, for the preparation of a medicament to treat or prevent dengue viral infections.

[00133] 50. Pharmaceutical formulation, according to any one of statements 1 to 41, for use as a medicament.

[00134] 51. Solid dosage form, according to any Petition 870260061215, dated 06 / 22 / 2026, p. 36 / 245 28 / 105 of declarations 42 to 46, for use as a medicine.

[00135] 52. Pharmaceutical formulation, according to any one of statements 1 to 41, for use in a method for treating or preventing dengue viral infections.

[00136] 53. Solid dosage form, according to any one of statements 42 to 46, for use in a method for treating or preventing dengue viral infections.

[00137] 54. Process for preparing a pharmaceutical formulation, as defined in any of statements 1 to 41, wherein the process comprises the steps of:

[00138] a) dissolve the API in a solvent to form a solution;

[00139] b) mix the methacrylic acid or hydroxypropyl methylcellulose copolymer or a combination thereof with the solution formed in step a), thus obtaining a mixture;

[00140] c) spray dry the mixture to obtain a solid dispersion;

[00141] d) optionally, mix the solid dispersion with at least one pharmaceutically acceptable excipient;

[00142] to provide a pharmaceutical formulation as defined in any of statements 1 to 41.

[00143] 55. Process, according to statement 54, wherein API is a compound of Formula (I):

[00144] a stereoisomeric form, a salt, solvate or pharmaceutically acceptable polymorph thereof; said compound being Petition 870260061215, dated 06 / 22 / 2026, p. 37 / 245 29 / 105 selected from the group in which:

[00145] Ri is H, R2 is Fe R3 is H or CH3,

[00146] Ri is H, CH3or F, R2is OCH3and R3is H, and

[00147] R1 is H, R2 is OCH3 and R3 is CH3.

[00148] R1 is CH3, R2 is F and R3 is H,

[00149] R1 is CF3 or OCF3, R2 is H and R3 is H,

[00150] R1 is OCF3, R2 is OCH3 and R3 is H, and

[00151] R1 is OCF3, R2 is H and R3 is CH3.

[00152] 56. Process, according to any of the statements and 55, where 0 API is: or a stereo-isomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof.

[00153] 57. Process for preparing a pharmaceutical formulation, according to any one of statements 1 to 41 or a solid dosage form, according to any one of statements 42 to 46, wherein the process comprises combining the active pharmaceutical ingredient with a methacrylic acid copolymer or a cellulose derivative (e.g., hydroxypropyl methylcellulose) to form the pharmaceutical formulation or the solid dosage form. Pharmaceutical formulations

[00154] The invention provides a pharmaceutical formulation comprising:

[00155] a) an active pharmaceutical ingredient (API) that is a dengue viral replication inhibitor; and

[00156] b1) methacrylic acid copolymer, or

[00157] b2) a cellulose derivative such as methyl cellulose (MC), ethyl Petition 870260061215, dated 06 / 22 / 2026, page 38 / 245 30 / 105 cellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) or a combination thereof.

[00158] In some embodiments, the cellulose derivative is HPMC.

[00159] In some embodiments, the pharmaceutical formulation according to the invention comprises an API that is a dengue viral replication inhibitor and at least one methacrylic acid copolymer.

[00160] For use in the present invention, the term methacrylic acid copolymer preferably refers to a copolymer / ester of acrylic and / or methacrylic acids, such as the compounds sold under the trade name Eudragit®. The Eudragit® compound is commercially available, for example, from Evonik Healthcare & Nutrition GmbH, Essen, Germany.

[00161] Different types of methacrylic acid copolymer can be used, and include poly(methacrylic acid-methyl methacrylate-co-methyl methacrylate) 1:1 (such as Eudragit® L-100, Eudragit® L12.5); poly(methacrylic acid-methyl methacrylate-co-methyl methacrylate) 1:2 (such as Eudragit® S-100, Eudragit® S12.5, Eudragit® FS30D); poly(methacrylic acid-ethyl acrylate-co-ethyl acrylate) 1:1 (such as Eudragit® L30D55, Eudragit® L100-55); poly(ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate-co-chloride) 1:2:0.1 (such as Eudragit® RS30D); poly(ethyl acrylate, methyl methacrylate, trimethylammonioethyl methacrylate chloride) 1:2:0.2 (such as Eudragit® RL30D); poly(ethyl acrylate-co-methyl methacrylate) 2:1 (such as Eudragit® NM 30D, or Eudragit NE 30D); cationic copolymer based on dimethyl aminoethyl methacrylate, butyl methacrylate and methyl methacrylate with a ratio of 2:1:1 (Eudragit® E-100) and combinations thereof.

[00162] In some embodiments, the methacrylic acid copolymer is selected from the group comprising an acid copolymer Petition 870260061215, dated 06 / 22 / 2026, page 39 / 245 31 / 105 methacrylic and methyl methacrylate; a copolymer of methacrylic acid and ethyl acrylate; and mixtures thereof.

[00163] In some embodiments, the methacrylic acid copolymer is a copolymer of methacrylic acid and methyl methacrylate. Preferably, the molar ratio between methacrylic acid and methyl methacrylate in the copolymer is 0.5:2 to 2:0.5, preferably 0.8:1 to 1.2:1 (e.g., 1:1).

[00164] In some embodiments, the methacrylic acid copolymer is poly(methacrylic acid-co-methyl methacrylate) 1:1 (EUDRAGIT® L100, CAS number: 25086-15-1).

[00165] In some embodiments, the pharmaceutical formulation according to the invention comprises an API that is a dengue viral replication inhibitor and hydroxypropyl methylcellulose.

[00166] In some embodiments, the pharmaceutical formulation according to the invention comprises a crystallization rate inhibitor. The term crystallization rate inhibitor refers to an excipient, for example, a polymeric excipient, which is added to the formulation with the aim of inhibiting the crystallization of an API when the formulation is administered to an individual. A crystallization rate inhibitor can be used to improve the bioavailability of an API where the bioavailability of the crystalline form is significantly lower compared to the amorphous / dissolved state. The crystallization rate inhibitor may be called a crystallization inhibitor or a stabilizer.

[00167] In one embodiment, the crystallization rate inhibitor is selected from polyvinylpyrrolidone (PVP), a polyvinylpyrrolidone-vinyl acetate copolymer (PVPVA), a poly(meth)acrylate polymer (e.g., methacrylic acid-methyl methacrylate copolymer), a cyclodextrin or a cyclodextrin derivative (e.g., (2-hydroxypropyl)-β-cyclodextrin (HPBCD), Petition 870260061215, dated 06 / 22 / 2026, page 40 / 245 32 / 105 hydroxypropyl cellulose, hydroxypropyl cellulose, methylcellulose, hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), a polyethylene glycol polyvinyl acetate-polyvinyl caprolactam graft copolymer, poly(vinyl alcohol), a poloxamer (e.g., poloxamer 188, 338 or 407) and any combinations thereof.

[00168] In one embodiment, the crystallization rate inhibitor is selected from hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), a polyethylene glycol-polyvinyl acetate-polyvinyl caprolactam graft copolymer, polyvinylpyrrolidone (PVP), and a polyvinylpyrrolidone-vinyl acetate copolymer (PVPVA), and a combination thereof. In another embodiment, the crystallization rate inhibitor is selected from hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone-vinyl acetate copolymer (PVPVA). The PVPVA may be a 1-vinyl2-pyrrolidone and vinyl acetate copolymer in a 6:4 mass ratio (PVPVA64).

[00169] Names and abbreviations for vinyl pyrrolidone-vinyl acetate copolymer include, but are not limited to, PVPVA, PVP-Vac copolymer, and poly(1-vinylpyrrolidone-co-vinyl-acetate).

[00170] Names and abbreviations for a copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate in a 6:4 mass ratio (PVPVA64) include, but are not limited to, copovidone, copovidum, and copovidone. Examples of commercially available PVPVA64 are Kollidon® VA64, Kollidon® VA64 Fine, Luviskol VA64®, and Plasdone S630®.

[00171] Names and abbreviations for polyvinylpyrrolidone include, but are not limited to, PVP, povidone, and crospovidone. Crospovidone is a cross-linked homopolymer of vinylpyrrolidone. An example of commercially available PVP is Plasdone® K-12. Petition 870260061215, dated 06 / 22 / 2026, page 41 / 245 33 / 105

[00172] Hydroxypropyl methylcellulose, also known as Hypromellose (HPMC), is an anhydroglucose in which some of the hydroxyl groups are replaced by methyl groups to form methyl ether moieties, and others are replaced by hydroxypropyl groups or by methoxypropyl groups to form hydroxypropyl ether or methoxypropyl ether moieties.

[00173] Hydroxypropyl methylcellulose (HPMC) polymers are available in different viscosity grades from various sources such as Dow Chemical Co. under the trade name Methocel® and together with Shin Etsu under the trade name Metolosse®. Examples of low viscosity polymers are Methocel E5®, Methocel E6®, Methocel E15LV®, Methocel E50LV®, Methocel K100LV® and Methocel F50LV®, whose 2% by weight aqueous solutions at 25 °C have viscosities of approximately 5 mPas, 6 mPas, 15 mPas, 50 mPas, 100 mPas and 50 mPas, respectively. Examples of medium viscosity HPMCs are Methocel E4M® and Methocel K4M®, whose 2% by weight aqueous solutions at 25 °C have viscosities of 4,000 mPas. Examples of high viscosity HPMCs are Methocel K15M® and Methocel K100M®, whose 2% by weight aqueous solutions at 25 °C have viscosities of 15,000 mPas and 100,000 mPas, respectively.

[00174] In some embodiments, hydroxypropyl methylcellulose has a viscosity in the range of 3 to 5,000 mPa.s in a 2% by weight solution in H2O at 25 °C, such as HPMC E5, HPMC E6, HPMC E15, HPMC E50, HPMC K4M, HPMC K15M, HPMC-AS and mixtures thereof. In some embodiments, hydroxypropyl methylcellulose has a viscosity in the range of 3 to 500 mPa.s in a 2% by weight solution in H2O at 25 °C, such as HPMC E5, HPMC E6, HPMC E15, HPMC E50 and mixtures thereof. In some embodiments, hydroxypropyl methylcellulose has a viscosity in the range of 3 to 50 mPa.s in a 2% by weight solution in H2O at 25 °C, such as HPMC E5, HPMC E6, Petition 870260061215, dated 06 / 22 / 2026, p. 42 / 245 34 / 105 HPMC E15, HPMC E50 and mixtures thereof.

[00175] In one embodiment, the invention provides a pharmaceutical formulation comprising a) an active pharmaceutical ingredient (API) that is a dengue viral replication inhibitor composed of Formula (I), as defined above and preferably a a stereoisomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof; and

[00176] b1) methacrylic acid copolymer, or

[00177] b2) a cellulose derivative such as methyl cellulose (MC), ethyl cellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) or a combination thereof. Preferably, the cellulose derivative is HPMC.

[00178] The pharmaceutical formulation of the invention may comprise at most about 50% by weight, at most about 40% by weight, at most about 35% by weight, at most about 30% by weight, or at most about 25% by weight of the API relative to the total weight of the formulation. The pharmaceutical formulation may comprise at least 0.1% by weight, at least 0.5% by weight, at least 1% by weight, at least 5% by weight, at least 10% by weight, at least 15% by weight, at least 17% by weight, or at least 20% by weight of the API relative to the total weight of the formulation. The pharmaceutical formulation may comprise from 0.1% to 45% by weight, from 0.5% to 40% by weight, from 1% to 40% by weight, from 5% to 35% by weight, or from 10% to 35% by weight of the API relative to the total weight of the formulation. Petition 870260061215, dated 06 / 22 / 2026, page 43 / 245 35 / 105

[00179] The pharmaceutical formulation of the invention may contain from 0.1 mg to 3,000 mg of the API, from 1 mg to 2,000 mg of the API, from 5 mg to 1,500 mg of the API, from 5 mg to 1,000 mg of the API, from 10 mg to 500 mg of the API, from 15 mg to 400 mg of the API, from 20 mg to 350 mg of the API, or any particular quantity or range comprised in the formulation. The therapeutically effective amount for said API will vary according to the diseases, syndromes, conditions, and disorders being prevented or treated.

[00180] The pharmaceutical formulation of the invention may comprise:

[00181] from 20 mg to 6,000 mg of methacrylic acid copolymer, from 30 mg to 4,000 mg of methacrylic acid copolymer, from 40 mg to 2,000 mg of methacrylic acid copolymer, from 50 mg to 1,500 mg of methacrylic acid copolymer, from 60 mg to 1,000 mg of methacrylic acid copolymer, from 70 mg to 1,000 mg of methacrylic acid copolymer, from 80 mg to 600 mg of methacrylic acid copolymer, or any specific quantity or range comprised in the formulation; or

[00182] 20 mg to 6,000 mg of hydroxypropyl methylcellulose, 30 mg to 4,000 mg of hydroxypropyl methylcellulose, 40 mg to 2,000 mg of hydroxypropyl methylcellulose, 50 mg to 1,500 mg of hydroxypropyl methylcellulose, 60 mg to 1,000 mg of hydroxypropyl methylcellulose, 70 mg to 1,000 mg of hydroxypropyl methylcellulose, 80 mg to 600 mg of hydroxypropyl methylcellulose, or any specific amount or range included in the formulation.

[00183] The pharmaceutical formulation of the invention may further comprise one or more diluents; wherein the formulation comprises from 20 mg to 7,500 mg of diluent, preferably from 30 mg to 6,500 mg, preferably from 40 mg to 4,500 mg, preferably from 50 mg to 2,500 mg, preferably from 60 mg to 2,000 mg, preferably from 80 mg to 1,000 mg, preferably from 90 mg to 550 mg of diluent, or any specific amount or range thereof. Petition 870260061215, dated 06 / 22 / 2026, page 44 / 245 36 / 105 in the formulation.

[00184] The pharmaceutical formulation of the invention may further comprise one or more surfactants; wherein the formulation comprises from 0.5 mg to 300 mg of the surfactant, preferably from 0.6 mg to 250 mg, preferably from 0.8 mg to 200 mg, preferably from 1 mg to 150 mg, preferably from 1.2 mg to 100 mg, preferably from 1.5 mg to 80 mg, preferably from 2 mg to 30 mg of the surfactant, or any specific amount or range comprised in the formulation.

[00185] The pharmaceutical formulation of the invention may further comprise one or more disintegrants; wherein the formulation comprises from 3 mg to 900 mg of the disintegrant, preferably from 4 mg to 850 mg, preferably from 5 mg to 600 mg, preferably from 6 mg to 500 mg, preferably from 7 mg to 400 mg, preferably from 7.5 mg to 200 mg, preferably from 8 mg to 100 mg of the disintegrant, or any specific quantity or range comprised in the formulation.

[00186] The pharmaceutical formulation of the invention may further comprise one or more flow agents; wherein the formulation comprises from 1 mg to 400 mg of the flow agent, preferably from 2 mg to 350 mg, preferably from 3 mg to 300 mg, preferably from 4 mg to 200 mg, preferably from 5 mg to 100 mg, preferably from 6 mg to 50 mg, preferably from 8.5 mg to 35 mg of the flow agent, or any specific amount or range comprised in the formulation.

[00187] The pharmaceutical formulation of the invention may further comprise one or more lubricants; wherein the formulation comprises from 0.5 mg to 200 mg of the lubricant, preferably from 1 mg to 150 mg, preferably from 3 mg to 100 mg, preferably from 4 mg to 90 mg, preferably from 7 mg to 90 mg, preferably from 8 mg to 80 mg, preferably from 10 mg to 50 mg of the lubricant, or any specific quantity or range comprised in the formulation.

[00188] The pharmaceutical formulation of the invention may comprise: Petition 870260061215, dated 06 / 22 / 2026, page 45 / 245 37 / 105

[00189] a maximum of 60% by weight, a maximum of 50% by weight, a maximum of 45% by weight, a maximum of 40% by weight, or a maximum of 35% by weight of methacrylic acid copolymer relative to the total weight of the formulation; or

[00190] maximum 60% by weight, maximum 50% by weight, maximum 45% by weight, maximum 40% by weight, or maximum 35% by weight of hydroxypropyl methylcellulose in relation to the total weight of the formulation.

[00191] The pharmaceutical formulation of the invention may comprise:

[00192] at least 0.2% by weight, at least 1% by weight, at least 5% by weight, at least 10% by weight, at least 20% by weight of methacrylic acid copolymer relative to the total weight of the formulation; or

[00193] at least 0.2% by weight, at least 1% by weight, at least 5% by weight, at least 10% by weight, at least 20% by weight of hydroxypropyl methylcellulose in relation to the total weight of the formulation.

[00194] A pharmaceutical formulation may include:

[00195] from 0.2% by weight to 60% by weight, from 1% by weight to 50% by weight, or from 5% by weight to 40% by weight of methacrylic acid copolymer relative to the total weight of the formulation; or

[00196] from 0.2% by weight to 60% by weight, from 1% by weight to 50% by weight, or from 5% by weight to 40% by weight of hydroxypropyl methylcellulose relative to the total weight of the formulation.

[00197] In some embodiments, the API and methacrylic acid copolymer are present in the pharmaceutical formulation of the invention in a ratio of 4:1 w / w; a ratio of 3.8:1 w / w; a ratio of 3.5:1 w / w; a ratio of 3.3:1 w / w; a ratio of 3:1 w / w; a ratio of 2.8:1 w / w; a ratio of 2.5:1 w / w; a ratio of 2.3:1 w / w; a ratio of 2:1 w / w; a ratio of 1.8:1 w / w; a ratio of 1.5:1 w / w; a ratio of 1:5 w / w; a ratio of 1:4.8 w / w; a ratio of 1:4.5 w / w; a ratio of 1:4.3 Petition 870260061215, dated 06 / 22 / 2026, p. 46 / 245 38 / 105 p / p; a ratio of 1:4 p / p; a ratio of 1:3.8 p / p; a ratio of 1:3.5 p / p; a ratio of 1:3.3 p / p; a ratio of 1:3 p / p; a ratio of 1:2.8 p / p; a ratio of 1:2.5 p / p; a ratio of 1:2.3 p / p; a ratio of 1:2 p / p; a ratio of 1:1.5 p / p or a ratio of 1:1.2 p / p or a ratio comprised within any two ratios mentioned herein, or a range or subrange of ratio within any two ratios mentioned herein.

[00198] In some embodiments, the API and hydroxypropyl methylcellulose are present in the pharmaceutical formulation of the invention in a ratio of 4:1 w / w; a ratio of 3.8:1 w / w; a ratio of 3.5:1 w / w; a ratio of 3.3:1 w / w; a ratio of 3:1 w / w; a ratio of 2.8:1 w / w; a ratio of 2.5:1 w / w; a ratio of 2.3:1 w / w; a ratio of 2:1 w / w; a ratio of 1.8:1 w / w; a ratio of 1.5:1 w / w; a ratio of 1:5 w / w; a ratio of 1:4.8 w / w; a ratio of 1:4.5 w / w; a ratio of 1:4.3 w / w; a ratio of 1:4 w / w; a ratio of 1:3.8 w / w; a ratio of 1:3.5 p / p; a ratio of 1:3.3 p / p; a ratio of 1:3 p / p; a ratio of 1:2.8 p / p; a ratio of 1:2.5 p / p; a ratio of 1:2.3 p / p; a ratio of 1:2 p / p; a ratio of 1:1.5 p / p or a ratio of 1:1.2 p / p or a ratio comprised within any two ratios mentioned herein, or a range or subrange of ratio within any two ratios mentioned herein.

[00199] The pharmaceutical formulation of the invention may further comprise one or more pharmaceutically acceptable excipients, as described in more detail herein. Pharmaceutically acceptable excipients include, but are not limited to, disintegrants, binders, diluents, lubricants, stabilizers, osmotic agents, colorants, plasticizers, coatings and the like. Additional suitable pharmaceutical excipients and their properties can be found in texts such as Handbook of Pharmaceutical Excipients, edited by RC Rowe, PJ Sheskey & PJ Weller, sixth edition (published by Petition 870260061215, dated 06 / 22 / 2026, page 47 / 245 39 / 105 Pharmaceutical Press, a division of the Royal Pharmaceutical Society of Great Britain. Thinners / fillers.

[00200] Useful diluents (or fillers) in the present invention include microcrystalline celluloses (e.g., Avicel® PH 102, Avicel® PH 101, Ceolus UF, Ceolus KG, or Ceolus PH), silicified microcrystalline celluloses, lactoses, sorbitols, celluloses, calcium phosphates, starches (e.g., partially or completely pregelatinized corn starch), sugars or lactoses (e.g., mannitol, sucrose, or similar) or any combination thereof. Examples of microcrystalline celluloses include a commercially available Avicel® series, such as microcrystalline celluloses that have a particle size of 100 μm (e.g., Avicel® PH 102). Microcrystalline celluloses also include commercially available Ceolus in UF, KG, or PH grades. Other examples of diluents include silicified microcrystalline celluloses, such as the commercially available Prosolv® series (e.g., Prosolv® SMCC 50 and SMCC HD90). Suitable lactoses for the invention include lactose monohydrate.The amounts of diluents in relation to the total weight of the pharmaceutical formulation can be from 5% by weight to 95% by weight, from 20% by weight to 80% by weight, from 25% by weight to 50% by weight, from 30% by weight to 48% by weight, from 30% by weight to 52% by weight, from 35% by weight to 52% by weight, or from 40% by weight to 50% by weight. For example, the diluent in the pharmaceutical formulation may comprise microcrystalline cellulose, silicified microcrystalline cellulose and corn starch, partially or completely pre-gelatinized, having a combined (or total) concentration of 5% by weight to 95% by weight, 20% by weight to 80% by weight, 25% by weight to 50% by weight, 30% by weight to 48% by weight, 30% by weight to 52% by weight, 35% by weight to 52% by weight, 30% by weight to 45% by weight, or so. Petition 870260061215, dated 06 / 22 / 2026, page 48 / 245 40 / 105 32.5% to 45% by weight relative to the weight of the pharmaceutical formulation. Disintegrators.

[00201] Disintegrants improve the dispersion of pharmaceutical formulations. Non-limiting examples of disintegrants useful in the present invention include croscarmellose (e.g., croscarmellose sodium), crospovidone, metal starch glycolates (e.g., sodium starch glycolate), and any combination thereof. Other examples of disintegrants include croscarmellose sodium (e.g., ac-Di-Sol®) and sodium starch glycolate. The pharmaceutical formulations of the present invention may comprise one or more disintegrants that provide a combined (or total) concentration of 1% by weight to 10% by weight, 5% by weight to 9% by weight, 6% by weight to 8% by weight, 6.5% by weight to 7.5% by weight, 6.75% by weight to 7.25% by weight, 3% by weight to 7% by weight, 1% by weight to 7% by weight, or 1.2% by weight to 8.2% by weight of the pharmaceutical formulation.In some embodiments, the pharmaceutical formulation comprises from 2% by weight to 8% by weight (for example, from 2.5% by weight to 7.5% by weight), preferably from 3% by weight to 6% by weight; more preferably, from 4% by weight to 5% by weight of disintegrant (for example, crospovidone) by weight of the pharmaceutical formulation. Binders.

[00202] Binders may include agents used during the production of granules of the active pharmaceutical ingredient by mixing the binder(s) with diluent and the active pharmaceutical ingredient. Some non-limiting examples of binders useful in the present invention include polyvinylpyrrolidones, sugar, modified celluloses (e.g., hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), and hydroxyethyl cellulose (HEC)), and any combination thereof. Other Petition 870260061215, dated 06 / 22 / 2026, page 49 / 245 41 / 105 examples of binders include polyvinylpyrrolidones (PVP). An example of HPC includes a low-viscosity polymer, HPC-SL. PVP can be characterized by its K-value, which is a useful measure of the viscosity of the polymer composition. PVP can be purchased commercially (e.g., Tokyo Chemical Industry Co., Ltd.) under the trade names Povidone® K12, Povidone® K17, Povidone® K25, Povidone® K30, Povidone® K60, and Povidone® K90. Specific examples of PVP include spray-dried soluble PVP. Another example includes PVP having an average molecular weight of 3,000 to 4,000, such as Povidone® K12 which has an average molecular weight of 4,000. PVP can be used in a wet or dry state.The pharmaceutical formulations of the present invention may comprise one or more binders that provide a combined (or total) concentration of 0.1% by weight to 50% by weight; 0.5% by weight to 43% by weight; 2% by weight to 45% by weight; 5% by weight to 40% by weight; 10% by weight to 35% by weight; 15% by weight to 30% by weight; 20% by weight to 25% by weight of the pharmaceutical formulation. In some embodiments, the pharmaceutical formulation comprises 0.5% by weight to 2% by weight (for example, 1.5% by weight to 2.0% by weight or 1.75% by weight to 2.25% by weight) of binder (for example, hydroxypropyl methylcellulose) relative to the weight of the pharmaceutical formulation. Lubricants.

[00203] Lubricants have the function of improving the compression and ejection of pharmaceutical formulations from, for example, a die press. Non-limiting examples of lubricants useful in the present invention include magnesium stearate, stearic acid (stearin), hydrogenated oil, sodium stearyl fumarate, Compritol (glyceryl behenate), and any combination thereof. In one example, the lubricant includes sodium stearyl fumarate. In another example, the lubricant includes magnesium stearate. Pharmaceutical formulations Petition 870260061215, dated 06 / 22 / 2026, page 50 / 245 42 / 105 of the present invention may comprise one or more lubricants providing a combined (or total) concentration of 0.1% by weight to 10% by weight, 0.5% by weight to 6% by weight, 0.8% by weight to 3.5% by weight, 1% by weight to 3% by weight, 1.5% by weight to 5.5% by weight, 2% by weight to 4% by weight, or 0.25% by weight to 5.25% relative to the weight of the pharmaceutical formulation. In some embodiments, the pharmaceutical formulation comprises 0.5% by weight to 5.5% by weight, preferably 1% by weight to 2.5% by weight of lubricant (e.g., magnesium stearate). Wetting agents / surfactants.

[00204] One or more wetting agents may be employed in the pharmaceutical formulations of the invention. Suitable wetting agents for the present invention generally improve the solubility of pharmaceutical formulations. Wetting agents include surfactants, such as nonionic surfactants and anionic surfactants. Non-limiting examples of surfactants useful in the invention include sodium lauryl sulfate (SLS), polyoxyethylene sorbitan fatty acids (e.g., polysorbate 20 (e.g., TWEEN 20™)), sorbitan fatty acid esters (e.g., Spans®), sodium dodecylbenzene sulfonate (SDBS), sodium dioctylsulfosuccinate (Docusate), sodium salt of deoxycholic acid (DOSS), sorbitan monostearate, sorbitan tristearate, sodium N-laurylsarcosine, sodium oleate, sodium myristate, sodium stearate, sodium palmitate, Gelucire 44 / 14, ethylenediaminetetraacetic acid (EDTA),dalpha-tocopheryl succinate, polyethylene glycol 1000 vitamin E (TPGS), lecithin, MW 677-692, monosodium glutamic acid monohydrate, Labrasol, PEG-8 caprylic / capric glyceride, Transcutol, diethylene glycol monoethyl ether, Solutol HS-15, Soluplus®, polyethylene glycol / hydroxystearate, taurocholic acid, polyoxypropylene and polyoxyethylene copolymers (e.g., poloxamers also), Petition 870260061215, dated 06 / 22 / 2026, page 51 / 245 43 / 105 known and commercially available under the trade name Pluronics®, such as Pluronic® L61, Pluronic® F68, Pluronic® F108 and Pluronic® F127), saturated polyglycolized glycerides (Gelucirs®), and any combinations thereof. Other examples include sodium lauryl sulfate, which is an anionic surfactant; and copolymers of polyoxypropylene and polyoxyethylene, which are nonionic surfactants. Examples of polyoxypropylene and polyoxyethylene copolymers include poloxamers, such as poloxamer with a polyoxypropylene molecular weight of 1,800 g / mol and an 80% polyoxyethylene content (e.g., poloxamer 188). The pharmaceutical formulations of the present invention may comprise one or more humectants that provide a combined (or total) concentration of 0.25% by weight to 10% by weight, 0.25% by weight to 5.75% by weight, 0.5% by weight to 5% by weight, 1% by weight to 3% by weight, or 1.5% by weight to 2% by weight relative to the weight of the pharmaceutical formulation.In some embodiments, the pharmaceutical formulation comprises from 0.25% by weight to 5% by weight (e.g., from 0.35% by weight to 4.5% by weight) of a humectant (e.g., sodium lauryl sulfate). Flow agents.

[00205] Flow agents enhance the flow properties of formulations during processing into the final pharmaceutical formulation. Non-limiting examples of useful flow agents in the present invention include silicon dioxide (e.g., colloidal pyrolyzed silica, colloidal anhydrous silica) and / or talc. Specific examples of flow agents include colloidal pyrolyzed silica (e.g., Aerosil® 200). The pharmaceutical formulations of the present invention may comprise one or more flow agents providing a combined (or total) concentration of 0.1% by weight to 10% by weight, preferably 1% by weight to 8% by weight; preferably 2% by weight to 7.5% by weight; preferably 3% by weight to 5%. Petition 870260061215, dated 06 / 22 / 2026, page 52 / 245 44 / 105 by weight, relative to the weight of the pharmaceutical formulation. In some embodiments, the pharmaceutical formulation comprises flow agent in an amount of 0.10% by weight to 5% by weight (e.g., 0.75% by weight to 3.25% by weight) relative to the weight of the pharmaceutical formulation. In other embodiments, the pharmaceutical formulation comprises pyrolyzed silica in an amount of 0.10% by weight to 2% by weight (e.g., 0.75% by weight to 1.5% by weight) relative to the weight of the pharmaceutical formulation.

[00206] Tablet dosage forms may additionally comprise a coating. Suitable coatings are film-forming polymers, such as those from the group of cellulose derivatives (such as HPC (hydroxypropyl cellulose), HPMC (hydroxypropoxy methylcellulose), MC (methylcellulose), HPMCAS (hydroxypropoxy methylcellulose acetate succinate), dextrins, starches, opdary®, natural gums, such as gum arabic, xanthan gums, alginates, polyvinyl alcohol, polymethacrylates and derivatives thereof, such as Eudragit®, which can be applied to the tablet as solutions or suspensions by means of various conventional methods, such as film coating.The coating is typically applied as a solution / suspension which, in addition to any film-forming polymer present, may also comprise one or more adjuvants, such as hydrophilic agents, plasticizers, surfactants, colorants and white pigments, such as, for example, titanium dioxide.

[00207] In some embodiments, the pharmaceutical formulation according to the invention comprises a plurality of granules forming an intragranular phase of the formulation and one or more excipients forming an extragranular phase of the formulation. Preferably, the pharmaceutical formulation comprises a tablet, said tablet comprising an intragranular phase and an extragranular phase. Petition 870260061215, dated 06 / 22 / 2026, page 53 / 245 45 / 105

[00208] As used herein, the term intragranular phase refers to the components of a formulation that are with granules and / or inside granules. As used herein, the term extragranular phase refers to the components of a formulation that are outside the granules.

[00209] In some embodiments, the intragranular phase of the pharmaceutical formulation according to the invention comprises the active pharmaceutical ingredient and one or a combination of methacrylic acid copolymer, or a cellulose derivative such as methylcellulose (MC), ethylcellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethylcellulose (CMC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC). In some embodiments, the intragranular phase of the pharmaceutical formulation according to the invention comprises the active pharmaceutical ingredient and one or a combination of methacrylic acid copolymer or hydroxypropyl methylcellulose (HPMC) and one or more excipients.

[00210] In some embodiments, the pharmaceutical formulation comprises at least 15% by weight; at least 20% by weight; at least 25% by weight; at least 28% by weight; at least 30% by weight; at least 34% by weight; at least 40% by weight; at least 45% by weight; at least 50% by weight; at least 55% by weight; at least 60% by weight; at least 65% by weight of the intragranular phase in relation to the total weight of the pharmaceutical formulation. In some embodiments, the pharmaceutical formulation comprises at most 99% by weight; at most 95% by weight; at most 93% by weight; at most 90% by weight; at most 85% by weight; at most 80% by weight; at most 75% by weight; at most 74% by weight; at most 73% by weight; at most 70% by weight; at most 67% by weight; a maximum of 63% by weight; a maximum of 60% by weight; a maximum of 53% by weight of the intragranular phase in relation to the total weight of the pharmaceutical formulation.

[00211] In some forms, the pharmaceutical formulation Petition 870260061215, dated 06 / 22 / 2026, page 54 / 245 46 / 105 comprises an intragranular phase comprising preferably 1% by weight to 70% by weight; preferably 2% by weight to 69% by weight; preferably 3% by weight to 68% by weight; preferably 4% by weight to 67% by weight; preferably 5% by weight to 66% by weight; preferably 6% by weight to 65% by weight; preferably 10% by weight to 64% by weight; preferably 15% by weight to 60% by weight; preferably 20% by weight to 55% by weight; preferably 25% by weight to 50% by weight; preferably 30% by weight to 45% by weight; preferably 35% to 40% by weight of the API relative to the total weight of the pharmaceutical formulation.

[00212] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising from 5% to 60% by weight; preferably from 7% to 55% by weight; preferably from 8% to 50% by weight; preferably from 17% to 45% by weight; preferably from 15% to 45% by weight of methacrylic acid or hydroxypropyl methylcellulose copolymer or a combination thereof in relation to the total weight of the pharmaceutical formulation.

[00213] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising from 5% to 60% by weight; preferably from 10% to 60% by weight; preferably from 12% to 60% by weight; preferably from 15% to 50% by weight; preferably from 18% to 45% by weight of the filler relative to the total weight of the pharmaceutical formulation.

[00214] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising from 1% by weight to 10% by weight; preferably from 1% by weight to 9% by weight, preferably from 1.7% by weight to 8% by weight; preferably from 1.6% by weight to 7.5% by weight; preferably from 2% by weight to 5% by weight of the disintegrant relative to the total weight of the pharmaceutical formulation.

[00215] In some forms, the pharmaceutical formulation Petition 870260061215, dated 06 / 22 / 2026, page 55 / 245 47 / 105 comprises an intragranular phase comprising from 0.1% by weight to 5% by weight; preferably from 0.2% by weight to 4.7% by weight; preferably from 0.5% by weight to 4.5% by weight; preferably from 0.8% by weight to 4% by weight; preferably from 1% by weight to 3.5% by weight of the flow agent relative to the total weight of the pharmaceutical formulation.

[00216] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising from 0.1% by weight to 5% by weight; preferably from 0.2% by weight to 4.7% by weight; preferably from 0.5% by weight to 4.5% by weight; preferably from 0.6% by weight to 4.5% by weight; preferably from 0.8% by weight to 4.0% by weight; preferably from 1% by weight to 3.5% by weight of the flow agent relative to the total weight of the pharmaceutical formulation.

[00217] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising from 0.1% by weight to 3% by weight; preferably from 0.2% by weight to 2.7% by weight; preferably from 0.5% by weight to 2.5% by weight; preferably from 0.7% by weight to 2% by weight of the lubricant relative to the total weight of the pharmaceutical formulation.

[00218] In some embodiments, the pharmaceutical formulation comprises at least 5% by weight; at least 7% by weight; at least 10% by weight; at least 15% by weight; at least 20% by weight; at least 25% by weight; at least 28% by weight; at least 30% by weight; at least 34% by weight; at least 35% by weight of the extragranular phase in relation to the total weight of the pharmaceutical formulation. In some embodiments, the pharmaceutical formulation comprises a maximum of 75% by weight; a maximum of 74% by weight; a maximum of 73% by weight; a maximum of 70% by weight; a maximum of 67% by weight; a maximum of 63% by weight; a maximum of 65% by weight; a maximum of 60% by weight; a maximum of 55% by weight; a maximum of 53% by weight; a maximum of 40% by weight of the extragranular phase. Petition 870260061215, dated 06 / 22 / 2026, page 56 / 245 48 / 105 extragranular in relation to the total weight of the pharmaceutical formulation. In some embodiments, the pharmaceutical formulation comprises at least 15% by weight and at most 75% by weight; at least 25% by weight and at most 70% by weight; at least 30% by weight and at most 65% by weight; at least 35% by weight and at most 60% by weight; at least 35% by weight and at most 70% by weight of the extragranular phase in relation to the total weight of the pharmaceutical formulation.

[00219] In some embodiments, the pharmaceutical formulation comprises at least 15% by weight; at least 20% by weight; at least 25% by weight; at least 28% by weight; at least 30% by weight; at least 34% by weight; at least 35% by weight of the intragranular phase in relation to the total weight of the pharmaceutical formulation. In some embodiments, the pharmaceutical formulation comprises at most 99% by weight; at most 93% by weight; at most 85% by weight; at most 80% by weight; at most 75% by weight; at most 74% by weight; at most 73% by weight; at most 70% by weight; at most 67% by weight; at most 65% by weight; at most 63% by weight; at most 60% by weight; at most 55% by weight; at most 53% by weight of the intragranular phase in relation to the total weight of the pharmaceutical formulation.In some embodiments, the pharmaceutical formulation comprises at least 15% by weight to a maximum of 75% by weight; at least 25% by weight to a maximum of 70% by weight; at least 30% by weight to a maximum of 65% by weight; at least 35% by weight to a maximum of 60% by weight; at least 35% by weight to a maximum of 70% by weight of the intragranular phase in relation to the total weight of the pharmaceutical formulation.

[00220] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising:

[00221] (i) 5% by weight to 45% by weight, 10% by weight to 40% by weight, 15% by weight to 35% by weight of the API in relation to the total weight of the pharmaceutical formulation;. Petition 870260061215, dated 06 / 22 / 2026, page 57 / 245 49 / 105

[00222] (ii) from 5% by weight to 60% by weight, from 10% by weight to 50% by weight, from 15% by weight to 55% by weight of methacrylic acid or hydroxypropyl methylcellulose copolymer or a combination thereof in relation to the total weight of the pharmaceutical formulation;

[00223] (iii) from 5% by weight to 45% by weight, from 10% by weight to 50% by weight, from 15% by weight to 40% by weight of the filler (e.g., mannitol, microcrystalline cellulose) in relation to the total weight of the pharmaceutical formulation;

[00224] (iv) from 1% by weight to 10% by weight, from 1.5% by weight to 9% by weight, from 1.5% by weight to 8% by weight of the disintegrant (e.g., croscarmellose sodium) in relation to the total weight of the pharmaceutical formulation;

[00225] (v) from 0.1% by weight to 5% by weight, from 0.2% by weight to 4.5% by weight, from 0.5% by weight to 4% by weight of flow agent (e.g., colloidal pyrolyzed silica) relative to the total weight of the pharmaceutical formulation;

[00226] (vi) from 0.1% by weight to 5% by weight, from 0.2% by weight to 4.5% by weight, from 0.5% by weight to 4% by weight of the surfactant (e.g., sodium lauryl sulfate) in relation to the total weight of the pharmaceutical formulation; and

[00227] (vii) from 0.1% by weight to 3% by weight, from 0.2% by weight to 2.5% by weight, from 0.5% by weight to 2% by weight of the lubricant (for example, magnesium stearate).

[00228] In some embodiments, the pharmaceutical formulation comprises an extragranular phase comprising from 0.1% by weight to 5% by weight; preferably from 0.2% by weight to 4.7% by weight; preferably from 0.5% by weight to 4.5% by weight; preferably from 1% by weight to 3.5% by weight; preferably from 1.5% by weight to 3% by weight of the disintegrant relative to the total weight of the pharmaceutical formulation. Petition 870260061215, dated 06 / 22 / 2026, page 58 / 245 50 / 105

[00229] In some embodiments, the pharmaceutical formulation comprises an extragranular phase comprising from 0.1% by weight to 3% by weight; preferably from 0.2% by weight to 2.7% by weight; preferably from 0.5% by weight to 2.5% by weight; preferably from 0.8% by weight to 2% by weight of the lubricant relative to the total weight of the pharmaceutical formulation.

[00230] In some embodiments, the pharmaceutical formulation comprises an extragranular phase comprising from 0.1% by weight to 55% by weight; from 0.2% by weight to 50% by weight; from 0.3% by weight to 45% by weight; from 0.4% by weight to 40% by weight; from 0.5% by weight to 35% by weight; from 0.6% by weight to 30% by weight; from 0.7% by weight to 25% by weight; from 0.8% by weight to 20% by weight; from 1% by weight to 15% by weight; from 1.3% by weight to 12% by weight; from 2% by weight to 10% by weight; from 2.5% by weight to 9% by weight; from 3% by weight to 8% by weight; from 4% by weight to 7% by weight; 5% to 6% by weight of the filler material relative to the total weight of the pharmaceutical formulation.

[00231] In some embodiments, the pharmaceutical formulation comprises an extragranular phase comprising:

[00232] (a) from 0.1% by weight to 5.0% by weight, from 0.2% by weight to 4.5% by weight, from 0.5% by weight to 3% by weight of the disintegrant (e.g., croscarmellose sodium) relative to the total weight of the pharmaceutical formulation;

[00233] (b) from 0.1% by weight to 3% by weight, from 0.2% by weight to 2.5% by weight, from 0.5% by weight to 2% by weight of the lubricant (e.g., magnesium stearate) relative to the total weight of the pharmaceutical formulation; and

[00234] (c) from 1% by weight to 15% by weight, from 1.5% by weight to 10% by weight or from 2% by weight to 8% by weight of the filler (e.g., hydroxypropyl methylcellulose) in relation to the total weight of the pharmaceutical formulation. Petition 870260061215, dated 06 / 22 / 2026, page 59 / 245 51 / 105

[00235] In some embodiments, the pharmaceutical formulation of the invention comprises an intragranular phase and an extragranular phase; wherein the formulation comprises from 50 mg to 17,000 mg of the intragranular phase, preferably from 80 mg to 10,000 mg, preferably from 100 mg to 5,000 mg, preferably from 120 mg to 3,000 mg, preferably from 150 mg to 2,500 mg, preferably from 200 mg to 2,000 mg, preferably from 250 mg to 1,200 mg of the intragranular phase, or any specific amount or range comprised in the formulation.

[00236] In some embodiments, the pharmaceutical formulation of the invention comprises an intragranular phase and an extragranular phase; wherein the formulation comprises from 4 mg to 1,500 mg of the extragranular phase, preferably from 6 mg to 1,000 mg, preferably from 8 mg to 500 mg, preferably from 10 mg to 300 mg, preferably from 15 mg to 250 mg, preferably from 20 mg to 200 mg, preferably from 30 mg to 100 mg of the extragranular phase, or any specific amount or range comprised in the formulation.

[00237] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising from 1 mg to 2,000 mg; preferably from 5 mg to 1,500 mg; preferably from 5 mg to 1,000 mg; preferably from 10 mg to 500 mg; preferably from 15 mg to 400 mg; preferably from 20 mg to 350 mg of API, or any specific amount or range comprised in the formulation.

[00238] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising from 20 mg to 6000 mg; preferably from 30 mg to 4000 mg; preferably from 40 mg to 2000 mg; preferably from 70 mg to 1000 mg of a copolymer of methacrylic acid or hydroxypropyl methylcellulose or a combination thereof, or any specific amount or range comprised in the formulation.

[00239] In some forms, the pharmaceutical formulation Petition 870260061215, dated 06 / 22 / 2026, page 60 / 245 52 / 105 comprises an intragranular phase comprising 10 mg to 6500 mg, preferably 12 mg to 5000 mg, preferably 15 mg to 4000 mg, preferably 15 mg to 2000 mg, preferably 18 mg to 1000 mg, preferably 18 mg to 500 mg of diluent / filler, or any specific amount or range included in the formulation.

[00240] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising 0.5 mg to 300 mg, preferably 0.6 mg to 250 mg, preferably 0.8 mg to 200 mg, preferably 1 mg to 150 mg, preferably 1.2 mg to 100 mg, preferably 1.5 mg to 80 mg, preferably 2 mg to 30 mg of surfactant, or any specific amount or range comprised in the formulation.

[00241] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising 2 mg to 720 mg, preferably 4 mg to 650 mg, preferably 5 mg to 400 mg, preferably 6 mg to 300 mg, preferably 7 mg to 200 mg, preferably 7.5 mg to 100 mg, preferably 8 mg to 60 mg of disintegrant, or any specific amount or range comprised in the formulation.

[00242] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising from 1 mg to 400 mg, preferably from 2 mg to 350 mg, preferably from 3 mg to 300 mg, preferably from 4 mg to 200 mg, preferably from 5 mg to 100 mg, preferably from 6 mg to 50 mg, preferably from 8.5 mg to 35 mg of flow agent, or any specific amount or range comprised in the formulation.

[00243] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising from 0.3 mg to 90 mg; preferably from 0.5 mg to 70 mg; preferably from 0.6 mg to 50 mg. Petition 870260061215, dated 06 / 22 / 2026, page 61 / 245 53 / 105 mg; preferably 0.7 mg to 25 mg, preferably 0.8 mg to 10 mg of lubricant, or any specific quantity or range included in the formulation.

[00244] In some embodiments, the pharmaceutical formulation comprises an intragranular phase comprising:

[00245] (i) from 1 mg to 2,000 mg; preferably from 5 mg to 1,500 mg; preferably 5 mg to 1,000 mg; preferably 10 mg to 500 mg; preferably 15 mg to 400 mg; preferably 20 mg to 350 mg of API;

[00246] (ii) from 20 mg to 6000 mg; preferably from 30 mg to 4000 mg; preferably from 40 mg to 2000 mg; preferably from 70 mg to 1000 mg of one of a copolymer of methacrylic acid or hydroxypropyl methylcellulose or a combination thereof;

[00247] (iii) 10 mg to 6,500 mg, preferably 12 mg to 5,000 mg, preferably 15 mg to 4,000 mg, preferably 15 mg to 2,000 mg, preferably 18 mg to 1,000 mg, preferably 18 mg to 500 mg of diluent / filler (e.g., mannitol, microcrystalline cellulose);

[00248] (iv) 2 mg to 720 mg, preferably 4 mg to 650 mg, preferably 5 mg to 400 mg, preferably 6 mg to 300 mg, preferably 7 mg to 200 mg, preferably 7.5 mg to 100 mg, preferably 8 mg to 60 mg of disintegrant (e.g., croscarmellose sodium);

[00249] (v) 1 mg to 400 mg, preferably 2 mg to 350 mg, preferably 3 mg to 300 mg, preferably 4 mg to 200 mg, preferably 5 mg to 100 mg, preferably 6 mg to 50 mg, preferably 8.5 mg to 35 mg of flow agent (e.g., colloidal pyrolyzed silica);

[00250] (vi) from 0.5 mg to 300 mg, preferably from 0.6 mg to 250 mg, preferably from 0.8 mg to 200 mg, preferably from 1 mg to 150 mg, Petition 870260061215, dated 06 / 22 / 2026, page 62 / 245 54 / 105 preferably 1.2 mg to 100 mg, preferably 1.5 mg to 80 mg, preferably 2 mg to 30 mg of surfactant (e.g., sodium lauryl sulfate); and

[00251] (vii) 0.3 mg to 90 mg; preferably 0.5 mg to 70 mg; preferably 0.6 mg to 50 mg; preferably 0.7 mg to 25 mg; preferably 0.8 mg to 10 mg of lubricant (e.g., magnesium stearate).

[00252] In some embodiments, the pharmaceutical formulation comprises an extragranular phase comprising 0.6 mg to 180 mg; preferably 1 mg to 100 mg; preferably 2 mg to 80 mg; preferably 3 mg to 50 mg; preferably 5 mg to 20 mg of disintegrant.

[00253] In some embodiments, the pharmaceutical formulation comprises an extragranular phase comprising 3.5 mg to 1100 mg; preferably 5 mg to 500 mg; preferably 10 mg to 250 mg; preferably 15 mg to 100 mg; preferably 25 mg to 90 mg of diluent / charge.

[00254] In some embodiments, the pharmaceutical formulation comprises an extragranular phase comprising 0.3 mg to 90 mg; preferably 0.5 mg to 70 mg; preferably 1 mg to 50 mg; preferably 1.5 mg to 20 mg; preferably 2 mg to 10 mg of lubricant.

[00255] In some embodiments, the pharmaceutical formulation comprises an extragranular phase comprising:

[00256] (a) from 0.6 mg to 180 mg; preferably from 1 mg to 100 mg; preferably 2 mg to 80 mg; preferably 3 mg to 50 mg; preferably 5 mg to 20 mg of disintegrant (e.g., croscarmellose sodium);

[00257] (b) from 0.3 mg to 90 mg; preferably from 0.5 mg to 70 mg; preferably from 1 mg to 50 mg; preferably from 1.5 mg to 20 mg; from Petition 870260061215, dated 06 / 22 / 2026, page 63 / 245 55 / 105 preference for 2 mg to 10 mg of lubricant (e.g., magnesium stearate); and

[00258] (c) from 3.5 mg to 1100 mg; preferably from 5 mg to 500 mg; preferably 10 mg to 250 mg; preferably 15 mg to 100 mg; preferably 25 mg to 90 mg of diluent / filler (e.g., hydroxypropyl methylcellulose).

[00259] Those skilled in the art will readily recognize that suitable pharmaceutically acceptable excipients are selected so that they are compatible with other excipients and do not bind or interact with the active pharmaceutical ingredient or cause degradation of the active ingredient or the pharmaceutical formulation.

[00260] It will be recognized that any of the above descriptions relating to the components of the pharmaceutical formulation may apply to any of the other aspects and embodiments of the invention. Active pharmaceutical ingredient

[00261] Suitable active pharmaceutical ingredients (APIs) are those that exert a pharmacological, immunological or metabolic action aimed at restoring, correcting or modifying physiological functions or producing a medical diagnosis.Examples, but not limited to, include analgesic and anti-inflammatory drugs; antiarrhythmic drugs; antibacterial and antiprotozoal agents; anticoagulants; antidepressants; antidiabetic drugs; antiepileptic drugs; antifungal agents; antihistamines; antihypertensive drugs; antimuscarinic agents; antineoplastic and antimetabolite agents; antimigraine drugs; anti-Parkinsonian drugs; antipsychotic, hypnotic, and sedative agents; antithrombotic agents; antitussives; antivirals; beta-adrenergic blockers; cardiac inotropic agents; corticosteroids; disinfectants; diuretics; enzymes; essential oils; gastrointestinal agents; lipid-regulating agents; local anesthetics; opioid analgesics; parasympathomimetic drugs; and... Petition 870260061215, dated 06 / 22 / 2026, page 64 / 245 56 / 105 anti-dementia; sex hormones; stimulant and vasodilator agents.

[00262] The invention provides a pharmaceutical formulation comprising:

[00263] a) an API; and

[00264] b1) methacrylic acid copolymer, or

[00265] b2) a cellulose derivative such as methyl cellulose (MC), ethyl cellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) or a combination thereof;

[00266] where API is a dengue viral replication inhibitor.

[00267] In particular, the API is in an amorphous form or dissolved state (i.e., molecular dispersion) in the pharmaceutical formulation.

[00268] In one embodiment, the API is a dengue viral replication inhibitor. Embodiments of the present invention include a pharmaceutical formulation described herein wherein the active pharmaceutical ingredient is a compound of Formula (I): ci R3(I)

[00269] a stereoisomeric form, a salt, solvate or pharmaceutically acceptable polymorph thereof; said compound being selected from the group in which:

[00270] Ri is H, R2 is F and R3 is H or CH3,

[00271] Ri is H, CH3or F, R2is OCH3and R3is H, and

[00272] Ri is H, R2 is OCH3, and R3 is CH3. Petition 870260061215, dated 06 / 22 / 2026, page 65 / 245 57 / 105

[00273] Ri is CH3, R2 is Fe R3 is Η,

[00274] Ri is CF3 or OCF3, R2 is H and R3 is H,

[00275] Ri is OCF3, R2 is OCH3, and R3 is H, and

[00276] Ri is OCF3, R2 is H and R3 is CH3.

[00277] Additional embodiments of the invention include pharmaceutical formulations, as described herein, wherein the API is a compound of Formula (I) selected from the group consisting of: Petition 870260061215, dated 06 / 22 / 2026, page 66 / 245 58 / 105 Cl Cl

[00278] its stereoisomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof.

[00279] In particular, the API is a compound of Formula (I), or an enantiomer, diastereomer or pharmaceutically acceptable salt form thereof.

[00280] In particular, the API is a compound of Formula (I), or an enantiomer, diastereomer or pharmaceutically acceptable salt form thereof, in an amorphous state or dissolved state (i.e., molecular dispersion).

[00281] In particular, the API used as starting material in the process for preparing a pharmaceutical formulation described herein is a compound of Formula (I), or an enantiomer, diastereomer, solvate or a pharmaceutically acceptable salt form thereof; whereas the API in the final pharmaceutical formulation or in the solid dosage form, as defined herein, is a compound of Formula (I), or an enantiomer, diastereomer or pharmaceutically acceptable salt form thereof, in amorphous form or dissolved state.

[00282] In a preferred embodiment, the compound of Formula (I) Petition 870260061215, dated 06 / 22 / 2026, page 67 / 245 59 / 105 the compound (a) or a stereoisomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof.

[00283] The API may be Compound (a) or a pharmaceutically acceptable solvate or salt form thereof. The API may be Compound (a) or a pharmaceutically acceptable salt form thereof. The API may be Compound (a) in a solvated form, for example, as a monohydrate. Preferably, the API is Compound (a). Preferably, the API is the (S) enantiomer of Compound (a). Preferably, the API is Compound (a) in anhydrous form. Preferably, the API is Compound (a) in amorphous form. Preferably, the API is Compound (a) or a pharmaceutically acceptable salt form thereof in amorphous form or dissolved state. Preferably, the API is Compound (a) in amorphous form or dissolved state. Preferably, the API is the (S) enantiomer of Compound (a) in amorphous form. Preferably, API is the (S) enantiomer of Compound (a) in anhydrous form.

[00284] In particular, the API used as starting material in the process to prepare a pharmaceutical formulation described herein is Compound (a), or a solvated form or a pharmaceutically acceptable salt form thereof; whereas the API in the final pharmaceutical formulation or solid dosage form is Compound (a) or a pharmaceutically acceptable salt form thereof in an amorphous form or dissolved state.

[00285] In particular, the API used as a starting material in the process for preparing a pharmaceutical formulation described herein is the Petition 870260061215, dated 06 / 22 / 2026, page 68 / 245 60 / 105 Compound (a) in a solvated form or a pharmaceutically acceptable salt form thereof; whereas the API in the final pharmaceutical formulation or solid dosage form is Compound (a) or a pharmaceutically acceptable salt form thereof in an amorphous form or dissolved state (i.e., molecular dispersion).

[00286] The compounds of Formula (I) can be synthesized according to the procedures disclosed in WO 2016 / 180696, which is incorporated herein in its entirety by reference.

[00287] It will be recognized that any of the above discussions relating to active pharmaceutical ingredients may apply to any embodiment of the pharmaceutical formulations, solid dosage forms, processes, uses and methods of prevention, treatment and viral inhibition described herein. For example, any reference to a dengue viral replication inhibitor may refer to a compound of Formula (I), or a stereoisomeric form, a salt, solvate, cocrystal or pharmaceutically acceptable polymorph thereof.

[00288] In a specific embodiment, the API in the pharmaceutical formulation described herein is Compound (a), or a stereoisomeric form, a salt, solvate, or pharmaceutically acceptable polymorph thereof. In a specific embodiment, the API in the pharmaceutical formulation described herein is Compound (a).

[00289] In a specific embodiment, the API in the pharmaceutical formulation described herein is a dengue viral replication inhibitor in amorphous form or dissolved state. In a specific embodiment, the API in the pharmaceutical formulation described herein is Compound (a) or a pharmaceutically acceptable salt form thereof, in amorphous form or dissolved state. In a specific embodiment, the API in the pharmaceutical formulation described herein is Compound (a) in amorphous form or dissolved state. Solid dosage form Petition 870260061215, dated 06 / 22 / 2026, page 69 / 245 61 / 105

[00290] The invention also provides a solid dosage form comprising a pharmaceutical formulation, as described herein.

[00291] The dosage form may be an oral dosage form (e.g., a capsule for oral administration). Alternatively, the dosage form may be an enteral dosage form. The solid dosage form may alternatively be a tablet.

[00292] The solid dosage form described herein (e.g., a tablet) may contain from 0.1 mg to 3,000 mg of the API, from 1 mg to 2,000 mg of the API, from 5 mg to 1,000 mg of the API, from 10 mg to 500 mg of the API, from 20 mg to 400 mg of the API, from 30 mg to 300 mg of the API, from 50 mg to 200 mg of the API, from 70 mg to 150 mg of the API, from 100 mg to 120 mg of the API, or any specific amount or range comprised in the formulation. The therapeutically effective amount for said API will vary according to the diseases, syndromes, conditions, and disorders being prevented or treated.

[00293] The solid dosage form described herein (e.g., a tablet) may contain from 0.5 mg to 1,000 mg of the API. In some embodiments, the solid dosage form may comprise from 0.5 mg to 800 mg, for example, from 1.0 mg to 600 mg, for example, from 2.0 mg to 450 mg; preferably the API is (Compound (a)), preferably the (S)-enantiomer of Compound (a). The solid dosage form may comprise at least 2 mg, at least 10 mg, at least 50 mg, at least 100 mg, at least 200 mg, at least 300 mg, at least 400 mg, or at least 500 mg of Compound (a).

[00294] In a specific embodiment, the solid dosage form Petition 870260061215, dated 06 / 22 / 2026, page 70 / 245 62 / 105 is a tablet that comprises:

[00295] a) an API; and

[00296] b1) methacrylic acid copolymer, or

[00297] b2) a cellulose derivative such as methyl cellulose (MC), ethyl cellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) or a combination thereof;

[00298] wherein the API is a dengue viral replication inhibitor.

[00299] In a specific embodiment, the solid dosage form is a tablet comprising:

[00300] a) an API;

[00301] b1) methacrylic acid copolymer, or

[00302] b2) hydroxypropyl methylcellulose (HPMC); and

[00303] d) one or more pharmaceutically acceptable excipients selected from disintegrants, binders, diluents, lubricants, stabilizers, wetting agents, flow agents, osmotic agents, colorants, plasticizers and coatings;

[00304] wherein the API is a dengue viral replication inhibitor.

[00305] In a specific embodiment, the solid dosage form is a tablet comprising a pharmaceutical formulation of the present invention.

[00306] In one embodiment, the solid dosage form comprises a pharmaceutical formulation, wherein the formulation comprises at least 5 mg, at least 15 mg, at least 25 mg, at least 50 mg, at least 55 mg, at least 100 mg, at least 150 mg, at least 200 mg, at least 250 mg, at least 300 mg, at least 350 mg, at least 400 mg, at least 450 mg or at least 500 mg of the API; preferably, the API is Petition 870260061215, dated 06 / 22 / 2026, page 71 / 245 63 / 105 or a pharmaceutically acceptable salt form thereof.

[00307] For oral administration, a solid dosage form is, in particular, provided in the form of tablets containing at least 1.0 mg, at least 0.5 mg, at least 1 mg, at least 5 mg, at least 10 mg, at least 20 mg, at least 30 mg, at least 40 mg, at least 50 mg, at least 60 mg, at least 70 mg, at least 80 mg, at least 90 mg, at least 100 mg, at least 110 mg, at least 120 mg, at least 130 mg, at least 140 mg, at least 150 mg, at least 160 mg, at least 170 mg, at least 180 mg, at least 190 mg, at least 200 mg, at least 210 mg, at least 220 mg, at least 230 mg, at least 240 mg, at least 250 mg, at least 260 mg, at least 270 mg, at least 280 mg, at least 290 mg, at least 300 mg, at least 310 mg, at least 320 mg, at least 330 mg, at least 340 mg, at least 350 mg, at least 360 mg, at least 370 mg, at least 380 mg, at least 390 mg, at least 400 mg, at least 410 mg, at least 420 mg, at least 430 mg, at least 440 mg, at least 450 mg, at least 460 mg, at least 470 mg, at least 480 mg,at least 490 mg, and at least 500 mg at least 510 mg, at least 520 mg, at least 530 mg, at least 540 mg, at least 550 mg, at least 560 mg, at least 570 mg, at least 580 mg, at least 590 mg, at least 600 mg, at least 610 mg, at least 620 mg, at least 630 mg, at least 640 mg, at least 650 mg, at least 660 mg, at least 670 mg, at least 680 mg, at least 690 mg, at least 700 mg, at least 710 mg, at least 720 mg, at least 730 mg, at least 740 mg, at least 750 mg, at least 760 mg, at least 770 mg, at least 780 mg, at least 790 mg, at least 800 mg, at least, Petition 870260061215, dated 06 / 22 / 2026, page 72 / 245 64 / 105 810 mg, at least 820 mg, at least 830 mg, at least 840 mg, at least 850 mg, at least 860 mg, at least 870 mg, at least 880 mg, at least 890 mg, at least 900 mg, at least 910 mg, at least 920 mg, at least 930 mg, at least 940 mg, at least 950 mg, at least 960 mg, at least 970 mg, at least 980 mg, at least 990 mg, at least 1,000 mg, at least 1,100 mg, at least 1,200 mg, at least 1,210 mg, at least 1,220 mg, at least 1,230 mg, at least 1,240 mg, at least 1,250 mg, at least 1,260 mg, at least 1,270 mg, to less than 1,280 mg, at least 1,290 mg, at least 1,300 mg, at least 1,410 mg, at least 1,320 mg, at least 1,330 mg, at least 1,340 mg, at least 1,350 mg, at least 1,360 mg, at least 1,370 mg, at least 1,390 mg, at least 1,400 mg of API or any value within the values ​​mentioned above. In particular, the solid dosage form comprises from 15 mg to 500 mg of API.

[00308] Advantageously, the API or solid dosage form can be administered as a single daily dose, or the total daily dosage can be administered in divided doses two, three, or four times a day. The daily dose can be kept unchanged throughout all or some days of a treatment or prevention period. Said daily dose can change over the days of a treatment or prevention period, such as being increased and / or decreased during the days of said treatment or prevention period. For example, the stated daily dose may remain unchanged for the first 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 days or more, followed by a lower and / or higher daily dose for the remaining days of the treatment or prevention period.The remaining days of the treatment or prevention period may be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 45, 46, 47, 48, 49, 50, 57. Petition 870260061215, dated 06 / 22 / 2026, p. 73 / 245 65 / 105 58, 59, 60 days or more. The API or solid dosage form may also be administered at least once a week, at least once every two weeks, at least once every three weeks, at least once every four weeks or a month, at least once every two months, at least once every three months, at least once every four months, at least once every five months, at least once every six months, or at least once a year.API or solid dosage form can also be administered daily for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 days or more consecutively. of at least one administration at least once a week, at least once every two weeks, at least once every three weeks, at least once every four weeks or a month, at least once every two months, at least once every three months, at least once every four months, at least once every five months, at least once every six months or at least once a year.

[00309] In certain embodiments, the API or solid dosage form may be administered in a first dose for a first duration (e.g., a loading phase) and in a second dose for a second period (e.g., maintenance phase).The loading phase may include administration of any of the dosages described herein (e.g., from about 10 mg to about 1,000 mg, from about 25 mg to about 800 mg, or from about 50 mg to about 400 mg). The initial duration of administration in the loading phase may be for any of the time periods contemplated in this document (e.g., from about 1 day to about 40 days, from about 3 days to about 20 days, or from about 5 days to about 10 days). The maintenance phase may include... Petition 870260061215, dated 06 / 22 / 2026, p. 74 / 245 66 / 105 administration of any of the dosages described herein (for example, from about 10 mg to about 1,000 mg, from about 25 mg to about 800 mg, or from about 50 mg to about 400 mg). The second duration of administration in the maintenance phase may be for any of the periods contemplated herein (for example, from about 1 day to about 60 days, from about 5 days to about 45 days, or from about 10 days to about 30 days).

[00310] The ideal dosages of the pharmaceutical formulation to be administered can be readily determined and will vary according to the specific compound used, the mode of administration, the strength of the preparation, and the progression of the disease, syndrome, condition, or disorder. The dosages mentioned above are, therefore, exemplifying the average case. Naturally, there may be individual cases where larger or smaller dosage ranges are warranted, and these are within the scope of the present invention.

[00311] The invention also provides a process for preparing a solid dosage form, as described herein. The process comprises the following steps:

[00312] a) dissolve the API in a solvent to form a solution;

[00313] b) mix methacrylic acid copolymer or hydroxypropyl methylcellulose or a combination thereof with the solution formed in step a), thus obtaining a mixture and, for example, further stirring the mixture;

[00314] c) spray dry the mixture to obtain a solid dispersion;

[00315] d) optionally, mix the solid dispersion with one or more pharmaceutically acceptable excipients;

[00316] provide a pharmaceutical formulation, as described herein.

[00317] As used herein, the term solid dispersion means a Petition 870260061215, dated 06 / 22 / 2026, page 75 / 245 67 / 105 Dispersion of an API in a solid matrix wherein the matrix comprises a small molecule or a polymer or a combination thereof.

[00318] The pharmaceutical formulation according to the present invention comprises a solid dispersion in which the matrix is ​​a polymer and the polymer is selected from methacrylic acid copolymer, or a cellulose derivative such as methylcellulose (MC), ethylcellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethylcellulose (CMC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC), or a combination thereof. Preferably, the cellulose derivative is HPMC.

[00319] The invention also provides a process for preparing a solid dosage form described herein, wherein the process comprises the steps of:

[00320] a) Dissolve the API in a solvent to form a solution;

[00321] b) Mix the methacrylic acid copolymer or a cellulose derivative such as methyl cellulose (MC), ethyl cellulose (EC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose, or a combination thereof, with the solution formed in step a), thus obtaining a mixture and, optionally, stirring the mixture further;

[00322] c) spray dry the mixture to obtain a solid dispersion;

[00323] d) optionally, mix the solid dispersion with one or more pharmaceutically acceptable excipients; for example, the pharmaceutically acceptable excipient may be selected from the group comprising fillers, surfactants, disintegrants, flow agents, lubricants and mixtures thereof;

[00324] e) compress the mixture into a tablet; Petition 870260061215, dated 06 / 22 / 2026, page 76 / 245 68 / 105

[00325] to provide a solid dosage form as described herein.

[00326] In some embodiments, the process for preparing a solid dosage form as described herein comprises the following steps:

[00327] a) Dissolve the API in a solvent to form a solution;

[00328] b) Mix the methacrylic acid or hydroxypropyl methylcellulose copolymer or a combination thereof with the solution formed in step a), thus obtaining a mixture and, optionally, stirring the mixture further;

[00329] c) spray dry the mixture to obtain a solid dispersion;

[00330] d) mix the solid dispersion with at least one filler, at least one surfactant, at least one disintegrant, at least one flow agent and at least one lubricant;

[00331] e) granulate the mixture;

[00332] f) mix the mixture obtained in step e) with at least one disintegrant, filler and at least one lubricant;

[00333] g) compress the mixture into a tablet;

[00334] to provide a solid dosage form as described herein.

[00335] In some embodiments, the solid dispersion can be obtained using hot melt extrusion. In some embodiments, the granulation step of the mixture is carried out using a roller compactor or by slugging.

[00336] Another aspect of the present invention provides a packaged pharmaceutical formulation, wherein the pharmaceutical formulation is any formulation described herein (for example, a tablet) sealed in a blister film, wherein the blister film comprises a formulation retention layer configured to retain one or more formulations. Petition 870260061215, dated 06 / 22 / 2026, page 77 / 245 69 / 105 pharmaceutical formulations (e.g., tablets) and a sealing layer configured to overlay the retention layer to seal the pharmaceutical formulation(s) within the retention layer, wherein the sealing layer comprises aluminum foil and a desiccant material. As used herein, the term desiccant material refers to any hygroscopic substance useful as a drying agent. Examples of desiccant materials include, without limitation, silica (e.g., silica gel), activated carbon, calcium sulfate, calcium chloride, and zeolite materials.

[00337] In some embodiments, the retention layer comprises one or more chambers, wherein each chamber is configured to retain one or more pharmaceutical formulations (such as any pharmaceutical formulation described herein (e.g., one or more tablets)) and each chamber is sealed by the sealing layer. In some embodiments, the retention layer comprises a transparent or opaque material (e.g., a transparent or opaque polyethylene material). In some embodiments, the sealing layer completely overlaps the retention layer and any chambers provided in the retention layer.

[00338] Examples of commercially available blister films useful to the present invention include Dessiflex Plus and Dessiflex Ultra available from Amcor plc. In some embodiments, the packaged pharmaceutical formulation consists of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 to 4, 2 to 10, or 1 to 10) tablets sealed in the blister film, the blister film comprising a cardboard. The stability and shelf life of the pharmaceutical formulations of the present invention are improved by using the blister film packaging of the invention, in which the sealing layer comprises a desiccant material, compared to packaging the pharmaceutical formulation in a blister film that has a sealing layer that does not have a desiccant material (e.g., blister film). Petition 870260061215, dated 06 / 22 / 2026, page 78 / 245 70 / 105 Aclar 400).

[00339] Another aspect of the present invention provides a kit comprising a packaged pharmaceutical formulation, such as any packaged pharmaceutical formulation described herein, and instructions for administering the packaged pharmaceutical formulation.

[00340] It will be recognized that any of the above discussions relating to solid dosage forms and processes for their preparation may apply to any modalities of solid dosage forms, prevention processes and treatments described herein. Prevention or treatment or inhibition methods

[00341] The present invention also encompasses the pharmaceutical formulations and solid dosages described herein for use as a medicament. The present invention further encompasses a method for preventing a dengue viral infection or for treating a dengue viral infection or for inhibiting the viral replication of a dengue virus in a biological sample in vitro or in an individual. The method comprises administering to the in vitro sample or to the individual (in need) an effective amount of the pharmaceutical formulations and solid dosages described herein. The in vitro sample or the individual is at risk of being infected by dengue virus.

[00342] The pharmaceutical formulations described herein may be administered in any of the dosage forms and regimens set forth above, or by means of the dosage forms and regimens established in the art, whenever the use of the pharmaceutical formulation is required for an individual who needs it.

[00343] The pharmaceutical formulations and dosage forms of the present invention are useful in methods for treating, improving and / or preventing a disease, syndrome, condition or disorder in an individual who needs them. These methods comprise, consist of and / or essentially consist of Petition 870260061215, dated 06 / 22 / 2026, page 79 / 245 71 / 105 administer to an individual, including an animal, a mammal, and a human being who needs such treatment, improvement, and / or prevention, a therapeutically effective amount of a formulation or dosage form described herein. In embodiments where the active pharmaceutical ingredient is a dengue viral replication inhibitor, the pharmaceutical formulations and dosage forms of the present invention are useful in methods for treating, improving, and / or preventing a disease, syndrome, or condition that is affected by the inhibition of dengue viral replication.

[00344] One embodiment of the present invention relates to a method of preventing a viral infection in an individual in need, including an animal, a mammal, and a human being who requires such prevention, wherein the method comprises administering to the individual a therapeutically effective amount of a pharmaceutical formulation or dosage form described herein.

[00345] One embodiment of the present invention is directed to a method for treating a dengue viral infection in an individual in need, including an animal, a mammal, and a human being who requires such treatment, wherein the method comprises administering to the individual a therapeutically effective amount of a pharmaceutical formulation or dosage form described herein.

[00346] One embodiment of the present invention relates to a method for inhibiting viral replication of a dengue virus in a needy individual, including an animal, a mammal, and a human being requiring such treatment, wherein the method comprises administering to the individual a therapeutically effective amount of a pharmaceutical formulation or dosage form described herein.

[00347] In certain modalities, the blood plasma level of API is at a level, for example, for the duration of the treatment regimen (for treatment or prevention), which is in the range of about Petition 870260061215, dated 06 / 22 / 2026, p. 80 / 245 72 / 105 from 5 ng / mL to about 10,000 ng / mL, from about 10 ng / mL to about 8,000 ng / mL, from about 15 ng / mL to about 6,500 ng / mL, from about 20 ng / mL to about 5,000 ng / mL, from about 25 ng / mL to about 4,500 ng / mL, from about 30 ng / mL to about 3,000 ng / mL, from about 40 ng / mL to about 2,000 ng / mL, or from about 50 ng / mL to about 1,000 ng / mL, or any single value or subrange therewith. In certain modalities, the maximum blood plasma level of API is up to approximately 10,000 ng / mL, up to approximately 8,000 ng / mL, up to approximately 6,500 ng / mL, up to approximately 4,500 ng / mL, up to approximately 3,000 ng / mL, up to approximately 2,000 ng / mL, up to approximately 1,000 ng / mL, or any single value or subrange therewith.In certain modalities, the minimum blood plasma level of API, for example, for the duration of the treatment regimen (for treatment or prevention), is at least about 5 ng / mL, at least about 10 ng / mL, at least about 15 ng / mL, at least about 20 ng / mL, at least about 25 ng / mL, at least about 30 ng / mL, at least about 40 ng / mL, at least about 50 ng / mL, or any single value or subrange therewith. The mentioned blood plasma levels can be obtained with any of the doses and / or dosing regimens described herein.

[00348] In another embodiment of the present invention, the pharmaceutical formulations described herein may be used in combination with one or more other medicinal agents, more particularly with other antiviral agents.

[00349] It will be recognized that variations to the foregoing embodiments of the invention may be made while still remaining within the scope of the invention. Each feature disclosed in this descriptive report, unless otherwise indicated, may be substituted for alternative features serving the same, equivalent, or similar purpose. Therefore, unless otherwise indicated, each feature disclosed is only an example of a generic series of Petition 870260061215, dated 06 / 22 / 2026, p. 81 / 245 73 / 105 equivalent or similar resources. Management methods

[00350] The pharmaceutically acceptable compounds and formulations described above may be administered to humans and other animals orally, rectally, intracystrally, intravaginally, intraperitoneally, topically (as by powders, ointments or drops), buccally, as an oral or nasal spray, or similarly, depending on the severity of the infection being prevented or treated.

[00351] Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compounds, liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents, solubilizing and emulsifying agents such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, peanut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols, and sorbitan fatty acid esters and mixtures thereof. In addition to inert diluents, oral formulations may also include adjuvants such as humectants, emulsifying and suspending agents, sweetening agents, flavorings, and fragrances.

[00352] Formulations for rectal or vaginal administration are specifically suppositories that can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or vehicles, such as cocoa butter, polyethylene glycol or a suppository wax, which are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. Petition 870260061215, dated 06 / 22 / 2026, page 82 / 245 74 / 105

[00353] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules.In such solid dosage forms, the active compound is mixed with at least one pharmaceutically acceptable inert excipient or vehicle, such as sodium citrate or dicalcium phosphate and / or a) diluents or extenders such as starches, lactose, sucrose, glucose, mannitol, silicic acid, b) binders such as, for example, carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and calcium carbonate, e) solution retarders such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin clay and bentonite, and i) lubricants such as talc, Calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof.In the case of capsules, tablets and pills, the dosage form may also include buffering agents.

[00354] Solid formulations of a similar type can also be used as diluents in soft and hard gelatin capsules with the use of excipients such as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like. Solid dosage forms of tablets, dragees, capsules, pills and granules can be prepared with coatings and wrappers such as enteric coatings and other coatings well known in the pharmaceutical formulation art. They may optionally contain opacifying agents and may also be of a formulation that releases the active ingredient only, or preferably, in a certain part of the intestinal tract, optionally in a delayed manner. Examples of incorporation formulations that can be used include substances Petition 870260061215, dated 06 / 22 / 2026, page 83 / 245 75 / 105 polymeric and waxy formulations. Solid formulations of a similar type may also be used as diluents in soft and hard gelatin capsules with the use of excipients such as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like.

[00355] The active compounds may also be in microencapsulated form with one or more excipients, as noted above. Solid dosage forms of tablets, dragees, capsules, pills, and granules may be prepared with coatings and wrappers such as enteric coatings, release-control coatings, and other coatings well known in the pharmaceutical formulation art. In such solid dosage forms, the active compound may be mixed with at least one inert diluent, such as sucrose, lactose, or starch. Such dosage forms may also comprise, as is normal practice, additional substances besides inert diluents, for example, tablet-forming lubricants and other tablet-forming aids, such as magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents.They may optionally contain opacifying agents and may also be of a formulation that releases the active ingredient only, or preferably, in a certain part of the intestinal tract, optionally in a delayed manner. Examples of incorporation formulations that may be used include polymeric substances and waxes.

[00356] Dosage forms for topical or transdermal administration of a compound described herein include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, or patches. The active component is mixed under sterile conditions with a pharmaceutically acceptable vehicle and any preservatives or buffers, as may be necessary. Ophthalmic formulations, Petition 870260061215, dated 06 / 22 / 2026, page 84 / 245 76 / 105 ear drops and eye drops are also contemplated as being within the scope of this invention. Additionally, the present invention contemplates the use of transdermal patches, which have the added advantage of providing controlled release of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the appropriate medium. Absorption enhancers can also be used to increase the flow of the compound through the skin. The rate can be controlled by providing a rate-control membrane or by dispersing the compound in a polymer or gel matrix.

[00357] The formulations described here can be administered orally, by inhalation spray, topically, rectally, nasally, buccally, vaginally, or through an implanted reservoir.

[00358] The pharmaceutical formulations described herein may be administered orally in any dosage form acceptable for buccal use, including, but not limited to, capsules, tablets, aqueous suspensions, or solutions. In the case of tablets for oral use, commonly used vehicles include, but are not limited to, lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in capsule form, useful diluents include lactose and dry corn starch. When aqueous suspensions are required for oral use, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening, flavoring, or coloring agents may also be added.

[00359] Alternatively, the pharmaceutical formulations described herein may be administered in the form of suppositories for rectal administration. These formulations may be prepared by mixing the agent with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature and, Petition 870260061215, dated 06 / 22 / 2026, page 85 / 245 77 / 105, therefore, will melt in the rectum to release the drug. These materials include, but are not limited to, cocoa butter, beeswax, and polyethylene glycols.

[00360] The pharmaceutical formulations described herein may also be administered topically, especially when the target for prevention and / or treatment includes areas or organs readily accessible by topical application, including diseases of the eye, skin, or lower intestinal tract. Suitable topical formulations are readily prepared for each of these areas or organs. Topical application for the lower intestinal tract may be done in a rectal suppository formulation (see above) or in a suitable enema formulation. Topically transdermal patches may also be used.

[00361] For topical applications, pharmaceutical formulations may be formulated in a suitable ointment containing the active component suspended or dissolved in one or more vehicles. Vehicles for topical administration of the compounds of this invention include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compound, emulsifying wax, and water. Alternatively, pharmaceutical formulations may be formulated in a suitable lotion or cream containing the active components suspended or dissolved in one or more pharmaceutically acceptable vehicles. Suitable vehicles include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl ester wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol, and water.

[00362] Pharmaceutical formulations can also be administered by nasal spray or inhalation. Such formulations are prepared according to well-known techniques in the pharmaceutical formulation art and can be prepared as solutions in Petition 870260061215, dated 06 / 22 / 2026, page 86 / 245 78 / 105 saline solution, employing benzyl alcohol or other suitable preservatives, absorption enhancers to intensify bioavailability, fluorocarbons and / or other conventional solubilizing or dispersing agents.

[00363] The compounds for use in the methods of the invention may be formulated in unit dosage form. The term unit dosage form refers to physically distinct units suitable as unit dosages for individuals undergoing prevention or treatment, with each unit containing a predetermined amount of active material calculated to produce the desired therapeutic effect, optionally in association with a suitable pharmaceutical vehicle. The unit dosage form may be for a single daily dose or for multiple daily doses (e.g., 1 to 4 or more times per day). When multiple daily doses are used, the unit dosage form may be the same or different for each dose.

[00364] All possible combinations of the embodiments indicated above are considered to be within the scope of this invention.

[00365] Reference is now made to the following examples which illustrate the invention in a non-limiting manner. General synthetic methods

[00366] Representative compounds for use in the present invention can be synthesized according to the general synthetic methods described below and illustrated in the following schemes. Since the schemes are merely illustrations, the invention should not be interpreted in a limiting manner by the chemical reactions and conditions described in the schemes and examples. Analogous compounds to the target compounds of these examples can be produced according to similar routes. The compounds presented are useful as pharmaceutical agents, as described in this invention. Petition 870260061215, dated 06 / 22 / 2026, p. 87 / 245 79 / 105 The various starting materials used in the schemes and examples are commercially available or can be prepared through methods within the practice of those skilled in the art. Compounds of Formula I.

[00367] The synthesis of compounds of general formula I can be carried out as described in Scheme 1. The 2-(4-chloro-2-methoxyphenyl) acetic acid (II) can be converted to the corresponding 2-(4-chloro-2-methoxyphenyl) acetyl chloride (III) with a chlorinating reagent such as, for example, thionyl chloride. The Friedel-Crafts reaction of the acid chloride (III) with a substituted indole of general formula (IV) can be carried out using a Lewis acid reagent such as, for example, EtsAlCl or TiCl4 in a suitable solvent such as, for example, CH2Cl2 or 1,2-dichloroethane and under suitable reaction conditions which typically (but not exclusively) involve cooling, to give the 3-acylated indole of general formula V.The introduction of an aniline moiety at the alpha position to the carbonyl moiety of compounds of general formula V can be achieved by a reaction sequence involving, for example, bromination of V with a reagent such as, for example, phenyltrimethylammonium tribromide in a suitable solvent such as, for example, THF (tetrahydrofuran), to give compounds of general formula VI, and subsequent reaction of the compounds of general formula VI with 3-methoxy-5-(methylsulfonyl)aniline (VII) in a suitable solvent such as, for example, CH3CN, and typically with the use of a base such as, for example, triethylamine (TEA) or N,n-diisopropylethylamine (DIPEA), to give compounds of general formula I as racemic mixtures. Chiral separation of compounds of general formula I can be done by, for example, chiral chromatography to give the A and B enantiomers of general formula I. Petition 870260061215, dated 06 / 22 / 2026, page 88 / 245 80 / 105 Enantiomers l(A) el(B) Scheme 1

[00368] In some cases, the synthesis of the intermediate of general formula V via the Friedel-Crafts synthesis approach is benefited by the presence of a protecting group (PG) on the N-indole during the Friedel-Crafts reaction step, as described in Scheme 2. To this end, the substituted indole of general formula IV can first be converted to an N-protected intermediate of general formula VIII, such as, for example, an N-tosylated intermediate of general formula VIII (PG = Ts), using a reagent such as, for example, tosyl chloride, in the presence of a base such as, for example, sodium hydride.The Friedel-Crafts reaction of substituted indole of general formula IV with acid(III) chloride can be carried out using a Lewis acid reagent such as, for example, E₂AlCl₂ or TiCl₂ in a suitable solvent such as, for example, CH₂Cl₂ or 1,2-dichloroethane, and under suitable reaction conditions that typically (but not exclusively) involve cooling, to give the N-protected 3-acylated indole of general formula IX. The removal of the PG protecting group from the N-indole intermediate of general formula IX can be done with a reagent such as, for example, Petition 870260061215, dated 06 / 22 / 2026, p. 89 / 245 81 / 105 LiOH (for PG = Ts) in a solvent mixture such as, for example, THF / water, at a suitable reaction temperature, to give the 3-acylated indole of general formula V. Cl Cl IV VIII IX V Scheme 2

[00369] As an alternative approach, the intermediate of general formula V can also be prepared as described in Scheme 3: The N-Boc protected substituted indole-3-carbaldehyde of general formula X can be converted to the corresponding Strecker type of intermediate of general formula XI by reaction with morpholine in the presence of reagents such as, for example, sodium cyanide and sodium bisulfite and in a suitable solvent such as, for example, a mixture of water and an organic solvent mixed with water such as, for example, dioxane. Alkylation of the compound of general formula XI with 4-chloro-2-methoxybenzyl chloride can be carried out in the presence of a base such as, for example, potassium hexamethyldisilazane and in a suitable solvent such as, for example, dimethylformamide (DMF) to give the compound of general formula XII.Subjecting the compound of general formula XII to a suitable aqueous acidic hydrolytic condition, such as treatment with an aqueous solution of hydrochloric acid at an elevated temperature, yields the intermediate of general formula V. Petition 870260061215, dated 06 / 22 / 2026, p. 90 / 245 82 / 105 Scheme 3

[00370] The compounds of Formula (I) can be synthesized according to the procedures disclosed in WO 2016 / 180696, which is incorporated herein in its entirety by reference. Examples

[00371] In the following examples, compound (a), preferably the (+)enantiomer of compound (a), is used as the active pharmaceutical ingredient (API). Compound (a) was synthesized as described in WO 2016 / 180696, under Example 9. It was obtained as a white powder: compound (a). Reactants Petition 870260061215, dated 06 / 22 / 2026, page 91 / 245 83 / 105 Chemical Name Company Methacrylic acid copolymer Methyl methacrylate Eudragit L100 Evonik Poly[methacrylic acid, ethyl acrylate] Eudragit L100-55 Evonik Hydroxypropyl methylcellulose E5 HPMC E5 Dow Hydroxypropyl methylcellulose succinate acetate HPMC-AS Shin-Etsu Hydroxypropyl methylcellulose succinate acetate HPMCAS MG Shin-Etsu Copovidone PVP VA 64 BASF Polyvinylpyrrolidone PVP K30 BASF Croscarmellose sodium: Ac-Di-Sol® DuPont Pharma Microcrystalline cellulose: Avicel® PH102 DuPont Pharma Colloidal pyrolyzed silica Aerosil® 200 Evonik Magnesium stearate N / A Avantor Sodium lauryl sulfate Kolliphor® SLS fine BASF Mannitol N / A Roquette Vitamin E TPGS N / A Isochem Example 1: Solid scattering screen

[00372] Solid dispersion formulations were prepared in a 96-well plate by a solvent evaporation method (transferring 100 μl of liquid containing the required amount of API and additives to each well, transferring the well plate to a vacuum oven at 70°C and pressure < 2 mbar for one hour, cooling to room temperature). The API (Compound (a) in amorphous form) and excipients were dissolved in a mixture of dichloromethane and methanol (50 / 50, v / v). The mixtures were prepared using an automated liquid handling workstation (Hamilton Microlab STAR plus). After dispensing, the amorphous films Petition 870260061215, dated 06 / 22 / 2026, page 92 / 245 84 / 105 of API polymer were generated by rapid evaporation of the organic solvent. This was done by evaporation under reduced pressure for one hour using a vacuum oven set at 70 °C and 200 mbar. The prepared solid dispersions are shown in Table A. The resulting films (12 replicates of each formulation per screen), each containing approximately 100 μg of API, were cooled and held at room temperature for one day for the first screening, and for 3 days for the second screening, before starting the dissolution test. The films were prepared with a constant percentage of API, 33% by weight, while the sum of the excipients was 67% by weight. For reference, a film containing only API was included. Table A: Solid dispersions tested Solid Dispersion Weight Ratio of API / Excipient 1 / Excipient 2* / Excipient 3* API Loading Dispersion 1 API / PVP K30 / Eudragit L100 (1 / 0.6 / 1.4) 100 μg Dispersion 2 API / PVP K30 / Eudragit L100 / SLS (1 / 0.6 / 1.37 / 0.04) 100 μg Dispersion 3 API / PVP K30 / HPMC E5 (1 / 0.6 / 1.4) 100 μg Dispersion 4 API / PVP K30 / Vit E TPGS (1 / 1.96 / 0.04) 100 μg Dispersion 5 API / PVP K30 (1 / 2) 100 μg Dispersion 6 API / PVP K30 / SLS (1 / 1.96 / 0.04) 100 μg Dispersion 7 API / PVP K30 / HPMC AS LG (1 / 0.6 / 1.4) 100 μg API Reference 100 μg *If present

[00373] A crystallinity assessment was performed by polarized light microscopy after film casting, on the day the dissolution study began, and after one, two, and four weeks of stability at 40°C / 75% humidity. No crystalline material could be detected after film casting, on the day the dissolution study began, and after one, two, and four weeks of stability at 40°C / 75% relative humidity. Petition 870260061215, dated 06 / 22 / 2026, p. 93 / 245 85 / 105

[00374] A miniaturized in vitro two-phase dissolution (SGF / FaSSIF) was performed, in which the amount of API dissolved was monitored as a function of time. Before starting the dissolution assay, the films were stored at room temperature for one day for the first screening and for three days for the second screening. By doing so, most of the residual solvent evaporated. The actual dissolution experiments were performed in 96 1 mL glass vials using the Hamilton STAR plus liquid handling platform for both sampling and sample preparation. Before addition to the films, the medium was preheated to 37 °C. 300 μL of preheated SGF (37°C, pH 1.3) was then added to the solid dispersions. After 15 minutes of incubation in SGF, 600 μL of preheated concentrated FaSSIF (37°C, pH 10.5) was added to the samples.The addition of this concentrated FaSSIF to SGF results in a medium with a composition similar to the typical FaSSIF medium used in one-phase dissolution studies. At predetermined time intervals (11, 24, 34, 49, 79, 139 minutes), aliquots were withdrawn from the dissolution medium and filtered through a 0.45 μm GHP membrane filter. Subsequently, the filtered solutions were quantitatively diluted with N-methylpyrrolidone (NMP) to avoid possible precipitation. The amount of API dissolved was determined by UPLC / UV-Vis analysis. The experiments were performed in duplicate for each formulation per screen.

[00375] Figure 1 shows the dissolution profiles of solid dispersions 1 to 7 (corresponding to concepts 1 to 7 in Figure 1) in SGFFaSSIF. A final release of approximately 9% of the total amount of API present in the films was measured for the pure amorphous API reference. All other solid dispersions tested show improved dissolution profiles compared to the reference. In the gastric phase, the API does not dissolve in any solid dispersion. For the Petition 870260061215, dated 06 / 22 / 2026, page 94 / 245 86 / 105 Solid dispersion 1 achieved a final release of 20% of the API.

[00376] A second solubility screening was performed as described above for solid dispersions 8 to 12 and their compositions listed in Table B. These solid dispersions were prepared as described above. Table B: Solid dispersions tested Solid Dispersion Weight Ratio of API / Excipient 1 / Excipient 2* / Excipient 3* API Loading Dispersion 8 API / Eudragit L100 (1 / 2) 100 μg Dispersion 9 API / PVP K30 / Eudragit L100 (1 / 0.6 / 1.4) at 100 μg Dispersion 10 API / PVP K30 / Eudragit L100 / SLS (1 / 0.6 / 1.37 / 0.04) at 100 μg Dispersion 11 API / HPMC E5 (1 / 2) 100 μg Dispersion 12 API / PVP K30 / HPMC E5 (1 / 0.6 / 1.4) at 100 μg *If present: solid dispersion was also tested on the first screen.

[00377] Figure 2 shows the dissolution profiles of solid dispersions 8 to 12 (corresponding to concepts 8 to 12 in Figure 2) in SGF-FaSSIF. A final release of approximately 9% of the total amount of API present in the films was measured for reference of pure amorphous API. For Dispersion 8, a final release of 54% of the API is achieved, while for Dispersion 9, a final release of 28% of the API was achieved. Example 2: Solubility screening

[00378] To test the appropriate solvent for spray drying, the approximate solubility of the starting material was estimated in different organic solvents at room temperature. Each solvent was added in increments of 50 μL or 100 μL to a 2 mL glass vial containing approximately 5 mg of each sample (API, Eudragit L100, and HPMC E5) until the solids were dissolved or a total volume of 1 mL was reached. The results Petition 870260061215, dated 06 / 22 / 2026, p. 95 / 245 87 / 105 are summarized in the table below. Table 1: Solubility screening of API, Eudragit L-100 and HPMC E5; S (solubility) in mg / mL Solvent\polymer API Eudragit L100 HPMC E5 Acetone / EtOH (1 / 1, v / v) S>100 S>100 S<3.3 Acetone / EtOH (2 / 1, v / v) S>100 S>100 S<3.3 Acetone / H2O (9 / 1, v / v) S>100 S>100 S<3.3 EtOH / H2O (9 / 1, v / v) 10 <S<12.5 S> 100 S<3.3*1 (directly co-solvent system) EtOH / H2O (9:1, v / v) N / AN / AS~25*2 (water first) Acetone / MeOH (2 / 1, v / v) S>100 N / AS<3.3 MeOH / DCM (1 / 1, v / v) S>100 150 <S<300 5~50* MeOH / DCM (3 / 1, v / v) N / A N / A 3,3~12,5* MeOH 42 S> 300 N / A *Transparent solution with very few particles, probably due to the intrinsic property of HPMC E5 itself. ** HPMC E5 was added directly to the mixture of organic solvent systems. * HPMC E5 was dissolved in water first, then the organic solvents were added.

[00379] The equilibrium solubility in MeOH and MeOH / dichloromethane (DCM) (1 / 1, v / v) was determined by UPLC and was 42 mg / mL and 317 mg / mL, respectively. Example 3: Spray drying

[00380] Based on the solvent selection and polymer screening results mentioned in the sections above, three polymers Petition 870260061215, dated 06 / 22 / 2026, p. 96 / 245 88 / 105 including Eudragit L100, HPMC AS and HPMC E5 were selected as carrier materials, Acetone / EtOH (2:1, v / v) (for Eudragit L100) and MeOH / DCM (1:1, v / v) (for HPMC E5 and HPMC AS) were selected respectively as solvent system for spray drying.

[00381] Sufficient quantities of different polymers were weighed into suitable glass bottles, respectively, and added with sufficient quantities of selected solvents to dissolve them. Approximately 25 g of Compound (a) (in the amorphous state) were then weighed and dissolved in each of the above solutions, respectively, to obtain clear solutions in Acetone / EtOH (2:1, v / v) at an API concentration of 14 mg / mL for Eudragit L100 and clear solutions in MeOH / DCM (1:1, v / v) at an API concentration of 10 mg / mL for HPMC E5 and HPMC AS, respectively. Approximately 35 g of Compound (a) were also weighed and dissolved in acetone to obtain the clear solution at an API concentration of 50 mg / mL to render the API amorphous.

[00382] Solid Dispersion 1 (SD1): API + Eudragit L100 (1:2 w / w).

[00383] Solid Dispersion 2 (SD2): API + HPMC E5 (1:2 w / w).

[00384] Solid Dispersion 3 (SD2): API + HPMC AS (1:2 w / w).

[00385] Spray drying apparatus: Buchi B-290. Table 2: Spray drying conditions and results API System SD1 SD2 SD3 Drug Load (% by weight) 100% 33.3% 33.3% 33.3% Mass Composition (g) 35 g 25g:50g 25g:50g 25g:50g API concentrate in SDD solution (mg / mL) 50 14 10 10 Petition 870260061215, dated 06 / 22 / 2026, page 97 / 245 89 / 105 Nozzle size (mm) 0.7 0.7 0.7 0.7 Solvent Acetone Acetone / EtOH (2 / 1, v / v) MeOH / DC M (1:1, v / v) MeOH / DC M (2:8, w / w) Inlet temperature (°C) 90 100 85 75 Outlet temperature (°C) 59 67 55 53 Nozzle airflow (m3 / mm) 40 50 40 40 Pump speed 50 40 50 50 Cyclone type High efficiency High efficiency High efficiency Standard Condenser temperature (°C) -21 -20 -20 -20 Efficiency (%) 86.4 73.8 80.4 86.5

[00386] Spray-dried dispersions (SDD) and spray-dried amorphous API powder were additionally dried under vacuum at a temperature below the Tg of the mixture. Example 4: Solid dispersion stability (SD):

[00387] The SD1, SD2 and SD3 powders obtained (i.e., SD1 based on Eudragit L100, SD2 based on HPMC E5, SD3 based on HPMC AS), after final post-drying, were weighed directly into flasks and configured for physical and chemical stability.

[00388] The appropriate quantity of each SD product was weighed into 40 mL glass vials (i.e., 12 mg for chemical stability and 50 mg for physical stability). The sample vials were then tightly sealed with gaskets and caps, wrapped in aluminum foil, and stored in the stability chamber at 25 °C / 60% relative humidity (RH) (closed) and 40 °C / 75% RH (closed) for Petition 870260061215, dated 06 / 22 / 2026, page 98 / 245 90 / 105 different time points (2 weeks, 1 month, 2 months, 3 months, and 6 months). Samples in triplicate were set up for chemical stability under each condition for each time point, and a single sample for physical stability. Compound (a), Eudragit L100, and HPMC E5 were also weighed into 40 mL glass vials and set up at each condition and time point for API and excipient control. The assay and impurity were tested for each condition at each time point for chemical stability, and XRPD, MLP, and mDSC were tested for physical stability.

[00389] The stability of SD1 as produced in Example 3 was tested by placing SD1 powder in glass bottles under stress conditions, as described in the first column of Table 3. Table 3: Physical and chemical stability of SD1 Storage conditions Time in months MLP XRPD Appearance Formulation Total impurities (%) Purity (%) Initial N / AN Am P1 1 0.93 99.07 2 0.93 99.07 25 °C 60 = closed; 1 MN Am P1 1 0.88 99.12 2 0.88 99.12 2 MN Am P1 1 0.91 99.09 2 0.91 99.09 3 MN Am P1 1 0.93 99.06 2 0.93 99.05 6 MN Am P1 1 0.91 99.09 2 0.91 99.09 40 °C 75% RH (closed) 1 MN Am P1 1 0.92 99.08 2 0.92 99.08 2 MN Am P2 1 0.97 99.03 2 0.99 99.01 3 MN Am P2 1 1.01 98.99 2 1.01 98.99 6 MN Am P2 1 0.95 99.05 2 0.98 99.02 UR: Relative humidity; M: Months; N: Non-birefringent; Am: Amorphous; P1: Soft white powder; P2: Soft white powder, and some of the powder could adhere to the bottom and to the surface. Petition 870260061215, dated 06 / 22 / 2026, page 99 / 245 91 / 105 flask wall; MLP: Polarized light microscope.

[00390] No obvious chemical and physical changes were observed after 6 months of storage in sealed glass bottles at 25°C and 60% relative humidity. However, an increase in total impurities was observed after 6 months of storage in sealed glass bottles at 40°C and 75% relative humidity, compared to the initial total impurities. Example 5: Stability of solid dispersion 2 (SD2):

[00391] The stability of SD2 as produced in Example 3 was tested by placing SD2 powder in glass bottles under stress conditions, as described in the first column of Table 4. Table 4: Physical and chemical stability of SD2. Storage Condition Time Points MLP XRPD Tg (°C) / m DSC Formulation Appearance Total Impurity (%) Purity (%) Initial N / AN Am 121.9 P3 1 0.87 99.13 2 0.89 99.11 25 °C 60% RH (closed) 1 MN Am 118.5 P3 1 0.83 99.17 2 0.83 99.17 2 MN Am 122.6 P3 1 0.86 99.14 2 0.87 99.13 3 MN Am 122.6 P3 1 0.86 99.14 2 0.87 99.13 6 MN Am 122.6 P3 1 0.83 99.18 2 0.82 99.19 40 °C 75% RH (closed) 1 MN Am 121.4 P3 1 0.83 99.16 2 0.84 99.16 2 MN Am 122.9 P3 1 0.87 99.13 2 0.87 99.13 3 MN Am 116.7 P3 1 0.88 99.12 2 0.88 99.12 6 MN Am 116.7 P3 1 0.84 99.16 2 0.84 99.16 UR: Relative humidity; M: Months; N: Non-birefringent; Am: Amorphous; P3: White powder, and some of the powder may adhere to the bottom and walls of the flask; MLP: Polarized light microscope. Petition 870260061215, dated 06 / 22 / 2026, pp. 100 / 245 92 / 105

[00392] Compared to the initial state, no obvious chemical or physical changes were observed after 6 months of storage in sealed glass bottles at 25°C / 60% relative humidity and 40°C / 75% relative humidity. Example 5A: Stability of solid dispersion 3 (SD3):

[00393] The stability of SD3 as produced in Example 3 was tested by placing SD3 powder in glass bottles under stress conditions, as described in the first column of Table 4A. Table 4A: Physical and chemical stability of SD3. Storage Condition Time Points ML P XRP D Tg (°C) / mD SC Appearance Formulation Total Impurity (%) Purity (%) Initial N / AN Am 109.5 P3 1 0.08 99.92 2 0.08 99.92 25°C 60% RH (closed) 2 SN Am 109.2 P3 1 0.10 99.91 2 0.10 99.90 1 MN Am 109.8 P3 1 0.13 99.87 2 0.13 99.87 3 MN Am 109.2 P3 1 0.16 99.84 2 0.16 99.84 40°C 75% RH (closed) 2 SN Am 109.4 P3 1 0.13 99.88 2 0.10 99.89 1 MN Am 109.8 P3 1 0.15 99.84 2 0.17 99.83 3 MN / A Am 109.0 P3 1 0.20 99.80 2 0.19 99.81 UR: Relative humidity; S: Weeks; M: Months; N: Non-birefringent; Am: Amorphous; P3: White powder, and some of the powder may adhere to the bottom and walls of the flask; MLP: Polarized light microscope.

[00394] Compared to the initial amount, the total impurities increased during storage in sealed glass bottles, particularly at 40°C and 75% relative humidity (from 0.08% at T0 to ~0.2% in 3 months). Example 5B: HPMC E5 Solid Dispersion Test

[00395] Four solid dispersions comprising different Petition 870260061215, dated 06 / 22 / 2026, p. 101 / 245 93 / 105 API / HPMC E5 weight ratios (listed below) were prepared as described in Example 3 above.

[00396] Solid dispersion 2a (SD2a): API + HPMC E5 (1:1 w / w)

[00397] Solid Dispersion 2b (SD2b): API + HPMC E5 (1:2 w / w)

[00398] Solid Dispersion 2c (SD2c): API + HPMC E5 (1:3 w / w)

[00399] Solid dispersion 2d (SD2d): API + HPMC E5 (1:4 w / w)

[00400] The prepared solid dispersions were tested in physiology-based dissolution tests (PBDT) using a simulated intestinal fluid as a medium. Dispersions SD2a, SD2b, SD2c, and SD2d were tested under fasting PBDT conditions. Dispersions SD2a, SD2b, and SD2d were tested under fed PBDT conditions. Details of the PBDT are provided in Tables 4B and 4B' respectively for fasting and fed conditions. Table 4B: PBDT for determining dissolution under fasting conditions. Parameter Method by PB Dissolution apparatus Paddle (USP type 2, Ph. Eur., JP) Dissolution medium temperature 37.0 ± 0.5°C Dissolution medium volume 900 mL Dissolution medium Phase 1 (15 minutes): 300 mL of SGF* pH 1.3 Phase 2 (2 hours): 900 mL of FaSSIF pH 6.5, 600 mL of FaSSIF** (preheated to 37°C) were added to the 300 mL of the Phase 1 solution. The total volume of FaSSIF pH 6.5 is 900 mL Paddle rotation speed 75 rpm Sample filter Whatman Spartan 0.2 μm RC (regenerated cellulose) membrane filter, 30 mm diameter, or equivalent. Petition 870260061215, dated 06 / 22 / 2026, page 102 / 245 94 / 105 HPLC analytical finishing with UV detection at 274 nm * Simulated gastric fluid; ** Simulated intestinal fluid in a fasting state Table 4B': PBDT for determining dissolution under fed conditions. Parameter Method by PB Dissolution apparatus Paddle (USP type 2, Ph. Eur., JP) Dissolution medium temperature 37.0 ± 0.5°C Dissolution medium volume 900 mL Dissolution medium Phase 1 (60 minutes): 300 mL phosphate buffer pH 4.9 2 g / L NaCl Phase 2 (3 hours): 900 mL FeSSIF pH 5.0, 600 mL of FeSSIF** (preheated to 37°C) were added to the 300 mL of the Phase 1 solution. The total volume of FeSSIF pH 5.0 is 900 mL Paddle rotation speed 75 rpm Sample filter Whatman Spartan 0.2 μm RC (regenerated cellulose) membrane filter, 30 mm diameter, or equivalent. Analytical finish HPLC with UV detection at 274 nm **Simulated intestinal fluid in a fed state**

[00401] Figure 3A shows the percentage of dissolution of the tested SD powders and Figure 3B shows the dissolution in mg of the same SD powders. SD2b and SD2c exhibit an improved dissolution profile compared to SD2a and SD2d. The improved dissolution profile was also observed for SD2b under PBDT-fed conditions, as can be seen in Figure 4.

[00402] In addition, the dissolution of the API and SD2a polymer, Petition 870260061215, dated 06 / 22 / 2026, page 103 / 245 95 / 105 SD2b, SD2c, and SD2d were evaluated in SGF-FaSSIF by adding 50 mg of each SD to 150 mL of pre-warmed SGF pH 1.3. After 15 min, 280 mL of pre-warmed 1.5x concentrated FaSSIF pH 10.3 were added to the SGF pH 1.3, resulting in FaSSIF pH 6.5. The samples were shaken at 250 rpm in an incubator at 37 °C. Time-dependent analysis was performed by taking 5 mL aliquots after 5' - 14' - 20' - 25' - 30' - 45' - 60' - 75' - 105' - 135'. The undissolved API was separated from the solution by filtration with a 25 mm Millex LCR filter with 0.45 μm PTFE (3 mL were discarded and 2 mL were used for concentration measurements). The solutions were diluted twice in ACN / water 50 / 50 v / v to avoid precipitation. The API concentration in the solution was determined using UPLC-UV. The HPMC E5 concentration in the solution was determined using UPLC-RI. Example 6: Stability of 10 mg SD1 tablets:

[00403] Tablets (10 mg strength) comprising SD1 have been prepared. The composition of the tablets is shown in Table 5. Table 5: Composition of the SD1 tablet (10 mg strength) Function Component %, by weight mg / tablet SDD Powder SD1 Powder comprising API 30.0% 30 Filler Mannitol 17.0% 17 Filler / binder Avicel PH102 45.0% 45 Surfactant SLS 1.0% 1 Disintegrant Croscarmellose sodium (Ac-Di-Sol) 5.0% 5 Flow agent Colloidal silicon dioxide (Aerosil 200) 1.0% 1 Lubricant Magnesium stearate 1.0% 1

[00404] The stability of the API, the SD1 powder, as well as the tablets (10 mg strength) comprising SD1 was tested by placing the tablets in high-density polyethylene (HDPE) bottles under Petition 870260061215, dated 06 / 22 / 2026, page 104 / 245 96 / 105 stress conditions, as described in column 2 of Table 6. The results are shown in Table 6. Table 6: Physical and chemical stability of 10 mg tablets prepared with Solid Dispersion 1. Sample Storage Condition Time Points XRP D Appearance Formulation Total Impurity (%) Purity (%) API 40 °C 75% RH (closed) 2 SN / A T1 1 1.05 98.95 1 MN / A T1 1 1.04 98.96 2 MN / A T1 1 1.06 98.94 3 MN / A T1 1 1.05 98.95 40 °C 75% RH (open) 2 SN / A T1 1 1.05 98.95 1 MN / A T1 1 1.06 98.94 2 MN / A T1 1 1.04 98.96 3 MN / A T1 1 1.04 98.96 SD1 Powder N / A Initial Am T1 1 1.15 98.85 40 °C 75% RH (closed) 2 S Am T1 1 1.26 98.75 1 M Am T1 1 1.33 98.67 2 M Am T1 1 1.35 98.65 3 M Am T1 1 1.30 98.70 40 °C, 75% RH (open) 2 S Am T1 1 1.16 98.84 1 M Am T1 1 1.16 98.84 2 M Am T1 1 1.12 98.88 3 M Am T1 1 1.14 98.86 Compressed N / A Initial Am T2 1 1.21 98.80 2 1.22 98.78 40 °C 75% RH (closed) 2 S Am T2 1 1.24 98.76 2 1.23 98.77 1 M Am T2 1 1.25 98.75 2 1.26 98.74 2 M Am T2 1 1.28 98.72 2 1.27 98.73 3 M Am T2 1 1.28 98.72 2 1.29 98.71 40 °C 75% RH (open) 2 S Am T2 1 1.16 98.84 2 1.16 98.84 1 M Am T2 1 1.15 98.85 2 1.16 98.84 2 M Am T2 1 1.13 98.87 2 1.13 98.87 3 M Am T2 1 1.13 98.87 2 1.12 98.88 RH: Relative humidity Petition 870260061215, dated 06 / 22 / 2026, page 105 / 245 97 / 105 S: week(s) M: Month(s) Am: amorphous; T1: white powder; T2: round, white or almost white tablet Example 7: Stability of 10 mg SD2 tablets:

[00405] Tablets (strength of 10 mg) comprising SD2 have been prepared. The composition of the tablets is shown in Table 7. Table 7: Composition of the SD2 tablet (10 mg strength) Function Component %, by weight mg / tablet SDD Powder SD2 Powder comprising API 30.0% 30 Filler Mannitol 17.0% 17 Filler / binder Avicel PH102 45.0% 45 Surfactant SLS 1.0% 1 Disintegrant Croscarmellose sodium (Ac-Di-Sol) 5.0% 5 Flow agent Colloidal silicon dioxide (Aerosil 200) 1.0% 1 Lubricant Magnesium stearate 1.0% 1

[00406] The stability of the API, SD2, as well as the tablet (10 mg strength) comprising SD2 was tested by placing the tablets in HDPE bottles under stress conditions, as described in column 2 of Table 7. The results are shown in Table 7. Table 8: Physical and chemical stability of 10 mg tablets prepared with Solid Dispersion 2. Tablet Storage conditions Time points XRPD Appearance Formulation Total impurities (%) Purity (%) API 40 °C 75% RH 2 SN / A T1 1 1.05 98.95 1 MN / A T1 1 1.04 98.96 Petition 870260061215, dated 06 / 22 / 2026, page 106 / 245 98 / 105 (Closed) 2 MN / A T1 1 1.05 98.94 3 MN / A T1 1 1.05 98.95 40 °C 75% RH (Open) 2 SN / A T1 1 1.06 98.95 1 MN / A T1 1 1.04 98.94 2 MN / A T1 1 1.04 98.96 3 MN / A T1 1 1.05 98.96 SD2 Powder N / A Initial Am T1 1 1.03 98.85 40 °C 75% RH (Closed) 2 S Am T1 1 1.05 98.75 1 M Am T1 1 1.07 98.67 2 M Am T1 1 1.09 98.65 3 M Am T1 1 1.08 98.70 40 °C 75% RH (open) 2 S Am T1 1 1.08 98.84 1 M Am T1 1 1.10 98.84 2 M Am T1 1 1.08 98.88 3 M Am T1 1 1.07 98.86 Compressed N / A Initial Am T2 1 1.04 98.80 2 1.04 98.78 40 °C 75% RH (closed) 2 S Am T2 1 1.04 98.76 2 1.04 98.77 1 M Am T2 1 1.05 98.75 2 1.06 98.74 2 M Am T2 1 1.07 98.72 2 1.07 98.73 3 M Am T2 1 1.08 98.72 2 1.07 98.71 40 °C 75% RH (open) 2 S Am T2 1 1.07 98.84 2 1.08 98.84 1 M Am T2 1 1.09 98.85 2 1.09 98.84 2 M Am T2 1 1.04 98.87 2 1.04 98.87 3 M Am T2 1 1.01 98.87 2 1.03 98.88 RH: Relative humidity S: week(s) Petition 870260061215, dated 06 / 22 / 2026, page 107 / 245 99 / 105 M: Month(s) Am: amorphous; T1: white powder; T2: round, white or almost white tablet Example 8: Tablet production Production of solid dispersions of SD1 Powder and SD2 Powder (see formulation in Table 8)

[00407] Methanol (for powder SD1) or a mixture of methanol and methylene chloride (1 / 1, v / v, for powder SD2) were transferred to a container and stirred using a mixer. During stirring, Compound (a) was added to the solvent. Stirring continued until Compound (a) dissolved. The resulting solution was filtered.

[00408] Eudragit L100 or hydroxypropyl methylcellulose E5 was added to the solution obtained in step 1. The mixture was stirred until completely combined.

[00409] The two mixtures were spray-dried using a suitable spray dryer (PSD-1) and the spray-dried products were collected.

[00410] The resulting powders were dried with a tray oven dryer and then collected. Table 9: Formulations for the preparation of SD1 powder and SD2 powder of solid dispersions Component (grams per 1,000 g of SD) Powder SD1 Powder SD2 Compound (a) 333.3 333.3 Methacrylic acid-methyl methacrylate copolymer (1:1) 666.7 NA Hydroxypropyl methylcellulose E5 NA 666.7 Methanol 14384.6 7107.5 Methylene chloride NA 11890.6 Petition 870260061215, dated 06 / 22 / 2026, page 108 / 245 100 / 105 Total lot size 1000 1000 Removed (by drying) during processing. Production of tablets comprising SD1 powder (see formulation in Table 8)

[00411] 1. SD1 powder, microcrystalline cellulose, mannitol, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, sodium lauryl sulfate were sifted together and then mixed in a pharmaceutical mixer.

[00412] 2. The mixture was compacted by rollers in a WP-120 roller compactor and the resulting granules were collected.

[00413] 3. Croscarmellose sodium and microcrystalline cellulose were sieved together and added to the dry granules obtained in step 2; the mixture was mixed in a pharmaceutical mixer.

[00414] 4. Extra sifted magnesium stearate was added and the resulting mixture was mixed in a pharmaceutical mixer.

[00415] 5. The final mixture was compacted into tablets using a Korsch XL 100 tablet press. Table 10: Tablet formulation comprising SD1 powder. RC Intra Ingredient Tablet 7 of 50 mg API (mg / tablet) Tablet 8 of 100 mg API (mg / tablet) Tablet 9 of 200 mg API (mg / tablet) Powder SD1 150 300 600 Mannitol 24 48 96 Microcrystalline cellulose 80 160 320 Sodium lauryl sulfate 4.5 9 18 Croscarmellose sodium 12 24 48 Colloidal silicon dioxide 6 12 24 Petition 870260061215, dated 06 / 22 / 2026, page 109 / 245 101 / 105 Magnesium stearate 1.5 3 6 RC Extra Croscarmellose sodium 3 6 12 Microcrystalline cellulose 17.5 35 70 Magnesium stearate 1.5 3 6 Total 300 600 1200 Production of tablets comprising SD2 powder (see formulation in Table 9)

[00416] 1. SD2 powder, microcrystalline cellulose, mannitol, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, sodium lauryl sulfate were sifted together and then mixed in a pharmaceutical mixer.

[00417] 2. The mixture was compacted by rollers in a WP-120 roller compactor and the resulting granules were collected.

[00418] 3. Croscarmellose sodium and microcrystalline cellulose were sieved together and added to the dry granules obtained in step 2; the mixture was mixed in a pharmaceutical mixer.

[00419] 4. Extra sifted magnesium stearate was added and the resulting mixture was mixed in a pharmaceutical mixer.

[00420] 5. The final mixture was compacted into tablets using a Korsch XL 100 tablet press. Table 11: Tablet formulation comprising SD2 powder. RC Intra Ingredient Tablet 10 of 50 mg API (mg / tablet) Tablet 11 of 100 mg API (mg / tablet) Tablet 12 of 200 mg API (mg / tablet) Powder SD2 150 300 600 Mannitol 24 48 96 Microcrystalline cellulose 80 160 320 Petition 870260061215, dated 06 / 22 / 2026, page 110 / 245 102 / 105 Sodium lauryl sulfate 4.5 9 18 Croscarmellose sodium 12 24 48 Colloidal silicon dioxide 6 12 24 Magnesium stearate 1.5 3 6 RC Extra Croscarmellose sodium 3 6 12 Microcrystalline cellulose 17.5 35 70 Magnesium stearate 1.5 3 6 Total 300 600 1200 Table 12: Evaluation of manufactured tablets comprising SD1 powder. Tablet 7 Tablet 9 Main compression force (KN) 7.9 0 to 9.0 91 to 10.0 91 to 16.5 91 to 17.5 91 to 20.6 Hardness (n=5,N) Min.(N) 110 131 135 218 251 355 Max. (N) 121 159 181 258 295 390 Average (N) 115.6 147.6 162.6 239.4 278 376.4 Friability (%):<0.5% N / A 0.0 N / AN / A 0.0 N / A Disintegration time (n = 6, mm:ss): 15 min First 0:45 2:04 3:23 1:16 2:11 4:40 Last 1:22 2:46 5:24 1:38 2:57 5:10 Table 13: Evaluation of manufactured tablets comprising SD2 powder. Tablet 10 Tablet 12 Main compression force (KN) 91 to 8.4 91 to 9.2 10.1 0 to 16.3 91 to 17.0 17.1 to 18.0 Hardness (n=5,N) Min.(N) 107 134 158 230 268 282 Petition 870260061215, dated 06 / 22 / 2026, page 111 / 245 103 / 105 Max. (N) 124 166 191 259 305 322 Average (N) 115.4 146.8 175.8 242.3 288.7 297.3 Friability (%): <0.5% 0.0 N / AN / AN / A 0.0 N / A Disintegration time (n = 6, mm:ss): 15 min First 2:14 3:27 5:35 2:38 4:43 4:20 Last 3:40 3:50 7:24 3:53 4:45 5:25 Example 9: Pharmacokinetics after oral administration of tablets in fasted dogs.

[00421] A pharmacokinetic (PK) study was conducted with tablets 7 and 10 mentioned above. The tablets were administered orally once, twice, or three times to male beagle dogs (N=3) in a fasting condition. The results are shown in Table 14. Table 14: Pharmacokinetics of fasting dogs at different doses Tablet 7 Tablet 10 Dose 50 mg / dog 2*50 mg / dog 50 mg / dog 2*50 mg / dog 3*50 mg / dog N 3 3 3 3 3 Cmax (ng / mL) 1320 ± 499 1680 ± 327 873 ± 123 2160 ± 385 2590 ± 996 Tmax (h) 4.00 (4.00 to 4.00) 4.00 (4.00 to 7.00) 4.00 (4.00 to 4.00) 4.00 (4.00 to 4.00) 4.00 (4.00 to 4.00) AUCultima (ng.h / mL) 22600 ± 4300 30000 ± 12300 13500 ± 2810 22300 ± 8210 42800 ± 21000 AUC» (h*ng / mL) 23500 ± 4550 30800 ± 13100 13800 ± 2860 22700 ± 8610 43100 ± 21200 Mean ± standard deviation AUC (Area under the curve) = area under the plasma concentration-time curve; AUCmax = AUC calculated up to the last point in time of the blood plasma level; AUC = AUC calculated using extrapolation of the plasma profile to infinite time; Cmax = maximum observed plasma concentration; N = number of animals; Tmax = time corresponding to the maximum observed plasma concentration; Petition 870260061215, dated 06 / 22 / 2026, page 112 / 245 104 / 105 Example 10: Pharmacokinetics after oral administration of tablets in fasted and fed dogs.

[00422] A pharmacokinetic (PK) study was conducted with tablets 9 and 12 mentioned above. Three tablets were administered orally to male beagle dogs (N=3) under fasted and fed conditions. The results are shown in Table 15. Table 15: Pharmacokinetics of dogs in fasted and fed states Tablet 9 Tablet 12 Fed Fasting Fed Fasting Fed Dose 200 mg *3 200 mg *3 200 mg *3 200 mg *3 N 3 3 3 3 Cmax (ng / mL) 6410 ±874 8540 ±1160 7380 ± 4460 12300 ±1790 Tmax (h) 7.00 (7.00 to 7.00) 7.00 (4.00 to 7.00) 7.00 (4.00 to 24.00) 7.00 (7.00 to 7.00) AUCultima (ng.h / mL) 139000 ± 26700 328000 ± 136000 222000 ± 156000 385000 ± 13500 AUC» (h*ng / mL) 140000 ± 27100 330000 ± 138000 223000 ± 157000 387000 ± 13900 Mean ± standard deviation AUC (Area under the curve) = area under the plasma concentration-time curve; AUCmax = AUC calculated up to the last point in time of the blood plasma level; AUC = AUC calculated using extrapolation of the plasma profile to infinite time; Cmax = maximum observed plasma concentration; N = number of animals; Tmax = time corresponding to the maximum observed plasma concentration;

[00423] Pharmacokinetic data clearly indicated that AUC values ​​were similar for fasting and fed states, indicating the absence of a food effect. Therefore, this formulation releases the API independently of the presence or absence of food. This is beneficial from a patient compliance standpoint. Therefore, a formulation according to the invention may result in a reduced food effect compared to others. Petition 870260061215, dated 06 / 22 / 2026, page 113 / 245 105 / 105 formulations.

[00424] Although preferred embodiments of the present invention have been shown and described herein, it will be evident to those skilled in the art that these embodiments are provided by way of example only. Numerous variations, alterations and substitutions will occur to those skilled in the art, without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in the practice of the invention and that embodiments within the scope of these claims and their equivalents are covered thereby.

Claims

1. Solid dosage form, characterized in that it comprises the pharmaceutical formulation comprising: a) an active pharmaceutical ingredient; and b1) a methacrylic acid copolymer, or b2) a cellulose derivative; wherein the active pharmaceutical ingredient is a dengue viral replication inhibitor of the formula: or a stereoisomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof.

2. Solid dosage form according to claim 1, characterized in that the viral replication inhibitor is the (S)enantiomer of:

3. Solid dosage form, according to claim 1 or 2, characterized in that the active pharmaceutical ingredient and a methacrylic acid copolymer or cellulose derivative are present in said formulation in a ratio of 4:1 w / w or 1:5 w / w.

4. Solid dosage form, according to any one of claims 1 to 3, characterized in that the methacrylic acid copolymer is selected from the group comprising a methacrylic acid-methyl methacrylate copolymer; a methacrylic acid-ethyl acrylate copolymer and a mixture thereof.

5. Solid dosage form, according to any one of claims 1 to 3, characterized in that the cellulose derivative has a viscosity in the range between 3 and 5,000 mPa.s in a 2% by weight solution in H2O at 25 °C and is selected from the group comprising HPMC E5, HPMC E6, HPMC E15, HPMC E50, HPMC K4M and HPMC-AS.

6. Solid dosage form, according to any one of claims 1 to 5, characterized in that it comprises a maximum of 40% by weight, preferably a maximum of 30% by weight, preferably a maximum of 25% by weight of the active pharmaceutical ingredient relative to the total weight of the formulation.

7. Solid dosage form, according to any one of claims 1 to 6, characterized in that it further comprises one or more pharmaceutically acceptable excipients selected from disintegrants, binders, diluents, lubricants, stabilizers, wetting agents, flow agents, osmotic agents, colorants, plasticizers and coatings.

8. Solid dosage form, according to any one of claims 1 to 7, characterized in that it comprises a plurality of granules forming an intragranular phase of the formulation and one or more excipients forming an extragranular phase of the formulation.

9. Solid dosage form, according to any one of claims 1 to 8, characterized in that it is an oral dosage form.

10. Solid dosage form, according to any one of claims 1 to 9, characterized in that it is a tablet.

11. Solid dosage form, according to any one of claims 1 to 10, characterized in that it comprises from about 0.5 mg to 1,000 mg of the active pharmaceutical ingredient; preferably, the formulation comprises from 1 mg to 1,000 mg of the active pharmaceutical ingredient; preferably, the formulation comprises from 2 mg to 500 mg of the active pharmaceutical ingredient.

12. Solid dosage form, according to any one of claims 1 to 11, characterized in that it comprises at least 0.5 mg of the active pharmaceutical ingredient; preferably at least 5 mg, preferably at least 10 mg, preferably at least 20 mg, preferably at least 50 mg, preferably at least 100 mg, preferably at least 200 mg, preferably at least 300 mg, preferably at least 400 mg, preferably at least 500 mg, or preferably at least 1000 mg of the active pharmaceutical ingredient.

13. Solid dosage form, according to any one of claims 1 to 12, characterized in that it is for the treatment or prevention of dengue viral infections.

14. Process for preparing a solid dosage form, as defined in any one of claims 1 to 13, characterized in that it comprises the steps of: a) dissolving the API in a solvent to form a solution; b) mixing the methacrylic acid copolymer or the cellulose derivative or a combination thereof with the solution formed in (a) to obtain a mixture; c) spray-drying the mixture to obtain a solid dispersion; d) optionally mixing the solid dispersion with at least one pharmaceutically acceptable excipient; e) compressing the mixture into a tablet; to provide a solid dosage form, as defined in any one of claims 18 to 29.

15. Process according to claim 14, characterized in that the active pharmaceutical ingredient is a dengue viral replication inhibitor of formula MeO O, preferably the (S)-enantiomer, or a stereoisomeric form, a pharmaceutically acceptable salt, solvate or polymorph thereof.

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