Tablet formulations involving alvelestat

Abstract

The present invention discloses a novel tablet formulation comprising alvelestat or a salt thereof, which has a higher drug loading than tablets previously known. Also disclosed herein are methods of administering the tablet to patients for treatment of various diseases. The disclosure also relates to the tablet of the invention for use in a method of treating a patient in need thereof.

Description

Tablet Formulations Involving AlvelestatCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of GB Application No. 2319953.2, filed 22nd December 2023. The contents of this application are incorporated herein by reference.FIELD OF THE INVENTION

[0002] The present invention discloses a novel tablet formulation comprising 6- methyl-5-(1-methyl-1H-pyrazol-5-yl)-N-{[5-(methylsulfonyl)pyridine-2-yl]methyl}-2-oxo-1-[3- (trifluoromethyl)phenyl]-1 ,2-dihydropyridine-3-carboxamide or a salt thereof.BACKGROUND OF THE INVENTION

[0003] WO 2005 / 026123, which is incorporated herein by reference in its entirety, teaches a class of neutrophil elastase (NE) inhibitors that are useful in therapy. WO 2005 / 026123 further discloses a specific NE inhibitor compound identified therein as 6- methyl-5-(1-methyl-1H-pyrazol-5-yl)-N-{[5-(methylsulfonyl)pyridin-2-yl]methyl}-2-oxo-1-[3- (trifluoromethyl)phenyl]-1 ,2-dihydropyridine-3-carboxamide and salts thereof (Example 94, page 85). This compound is known as alvelestat, AZD9668, or MPH966.

[0004] NE has been implicated in the promotion or exacerbation of a number of diseases such as pulmonary emphysema, pulmonary fibrosis, adult respiratory distress syndrome (ARDS), ischemia reperfusion injury, rheumatoid arthritis and pulmonary hypertension.

[0005] WO 2010 / 094964, which is incorporated herein by reference in its entirety, teaches salt forms of alvelestat. In particular, this document discloses alvelestat tosylate(the 4-methylbenzenesulfonate salt of alvelestat) and tablet dosage forms comprising 39.5 mg alvelestat tosylate, corresponding to 30 mg alvelestat free base. This document reports that alvelestat is administered in a maximum daily amount of 200 mg per day.

[0006] WO 2021 / 209739, which is hereby incorporated by reference in its entirety, discloses dosage regimens for the treatment of patients with a disease mediated by a-1 antitrypsin deficiency with alvelestat.

[0007] It has been determined that, to avoid NE activation, and hence, avoid damage associated with NE in diseases of the respiratory system which are mediated by a-1 antitrypsin deficiency, such as COPD, inhibitory treatment must achieve and maintain a threshold Cmin (trough plasma concentration) in a human of 300 nM or above.

[0008] To date, 12 clinical trials have been conducted using alvelestat in non-CF bronchiectasis, CF, bronchiolitis obliterans syndrome, and COPD. These trials compared placebo to alvelestat 60 mg twice per day and plasma alvelestat levels averaged 200 nM, suggesting the 60mg dose was at the lower end of the dose range to achieve adequate target engagement. Thus, a higher dose of alvelestat is needed to achieve the IC95 (plasma alvelestat concentration of >300 nM).

[0009] In Phase 2 clinical trials, alvelestat improved lung function in bronchiectasis, reduced markers of elastin degradation in CF, and reduced inflammatory markers in non- AATD patients with COPD. In all previous trials, alvelestat was well tolerated with no treatment emergent significant adverse events, ECG or vital sign changes, and no dose related liver function abnormalities were observed.

[0010] In later trials, alvelestat was administered in higher doses, e.g. 120 mg twice daily or 240 mg twice daily. More response has been seen in patients from the administration of the higher dose of 240 mg twice daily. For example, in the ASTRAEUS trial, the 240 mg twice daily dose demonstrated significant and consistent reductions in all three biomarkers related to AATD lung disease activity blood neutrophil elastase (NE), Aa- val360and the elastin breakdown product, desmosine, whereas 120 mg only showed a reduction of neutrophil elastase activity. This suggests that higher doses of alvelestat are more preferable.

[0011] However, in each clinical trial thus far, alvelestat has been supplied to patients in tablets comprising a 30 mg dose of alvelestat (as 39.5 mg alvelestat tosylate). This means that, to give doses of 120 mg or 240 mg twice daily, a patient must take 8 or 16 tablets a day. This number of tablets can be overwhelming for patients and cause a reduction in patient adherence. Therefore, there is a need for a tablet containing a higher dose of alvelestat to reduce the pill burden and to improve patient adherence.

[0012] Achieving this goal is not straightforward. Each 30 mg alvelestat tablet used in clinical trials comprises 10 wt% of alvelestat tosylate, and has a total tablet core weight of 400 mg. Scale-up of the 30 mg tablet, to make a 120 mg tablet, while retaining the same composition would not be feasible, as the total weight of such tablets would be at least 1600 mg. This would be a very large tablet that may cause discomfort in patients and may be difficult to swallow.

[0013] Moreover, increasing the drug loading of alvelestat in the tablet was also believed to be challenging. Previous experiments showed that increasing the alvelestat drug loading beyond 11.4 % (i.e. more than 15 wt% of alvelestat tosylate) resulted in poor tablet properties. For example, poor dissolution, as shown in Fig 1.

[0014] Additionally, salt forms of alvelestat have very low bulk density and poor powder flow. For example, the Carr Index (43%) and Hausner Ratio (1.74) of alvelestat tosylate mean that alvelestat tosylate is classified as ‘very, very poor flow’.

[0015] The overall physical properties and manufacturability of low drug load formulations are determined predominantly by the inactive ingredients or excipients in the formulation. However, at higher drug loading, the contribution of the physical properties of the active pharmaceutical ingredient (“API”) to the manufacturability of a formulation increases. A higher drug loading of alvelestat would therefore be expected to result in poorer manufacturability with respect to flowability and bulk density of the powder blend. A decrease in manufacturability occurred with tablets which contained above 10 wt% of alvelestat tosylate (corresponding to 7.6 wt% alvelestat free base, where, as used herein, the amount of alvelestat free base corresponds to the amount of the alvelestat compound within a given tablet).

[0016] Therefore, there is a need to overcome these challenges by providing tablets comprising higher doses of alvelestat, e.g. 60 mg and 120 mg doses. There is also a need to provide higher drug load tablets which maintain good dissolution profiles and good processability.SUMMARY OF THE INVENTION

[0017] The tablets provided herein have a higher drug loading of alvelestat than previously known tablets. They provide good dissolution properties, and they have sufficient processability. This allows alvelestat to be provided to patients in higher dose tablets, which reduces the pill burden for patients and improves adherence to therapy.

[0018] The invention relates to a tablet comprising alvelestat or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, whereinthe tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 10 wt% of alvelestat free base, wherein the tablet comprises an amount of alvelestat or a pharmaceutically acceptable salt thereof that corresponds to about 60 mg to about 120 mg of alvelestat free base.

[0019] The invention also relates to a tablet comprising alvelestat or a pharmaceutically acceptable salt thereof, wherein the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to about 120 mg of alvelestat free base; and wherein the tablet comprises one or more pharmaceutically acceptable excipients.

[0020] The invention also relates to a tablet comprising alvelestat or a pharmaceutically acceptable salt thereof, wherein the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to about 60 mg of alvelestat free base; and wherein the tablet comprises one or more pharmaceutically acceptable excipients.

[0021] The invention also relates to a method of treatment of a disease which is mediated by a-1 antitrypsin deficiency wherein the method comprises administering one or more tablet(s) of the invention to a subject in need thereof.

[0022] The invention also relates to alvelestat or a pharmaceutically acceptable salt thereof for use in a method of treatment of a disease which is mediated by a-1 antitrypsin deficiency wherein the method comprises administering one or more tablet(s) according to the invention to a subject in need thereof.

[0023] The invention also relates to the use of alvelestat or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treatment of a disease which is mediated by a-1 antitrypsin deficiency wherein the method comprises administering one or more tablet(s) according to the invention to a subject in need thereof.

[0024] In preferred embodiments of the invention, the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to about 60 mg or 120 mg of alvelestat free base.

[0025] In preferred embodiments of the invention, alvelestat is provided as alvelestat tosylate.

[0026] In preferred embodiments of the invention, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 15 wt% and at most about 25 wt% of alvelestat free base; at least about 40 wt% and at most about 70 wt% microcrystalline cellulose; at least about 3 wt% and at most about 15 wt%cross-linked polyvinylpyrrolidone; at least about 0.5 wt% and at most about 2.5 wt% sodium lauryl sulfate; at least about 5 wt% and at most about 10 wt% calcium hydrogen phosphate dihydrate; and at least about 0.5 wt% and at most about 2 wt% sodium stearyl fumarate. In particular, such a tablet may comprise at least about 20 wt% and at most about 33 wt% of alvelestat tosylate.

[0027] In preferred embodiments of the invention, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 15 wt% and at most about 25 wt% of alvelestat free base; at least about 50 wt% and at most about 62 wt% microcrystalline cellulose; at least about 4.5 wt% and at most about 11 wt% cross-linked polyvinylpyrrolidone; at least about 1.1 wt% and at most about 2.2 wt% sodium lauryl sulfate; at least about 5 wt% and at most about 10 wt% calcium hydrogen phosphate dihydrate; and at least about 0.5 wt% and at most about 2 wt% sodium stearyl fumarate. In particular, such a tablet may comprise at least about 20 wt% and at most about 33 wt% of alvelestat tosylate.

[0028] In preferred embodiments of the invention, the tablet consists of at least about 20 wt% and at most about 33 wt% alvelestat tosylate; at least about 40 wt% and at most about 70 wt% microcrystalline cellulose; at least about 3 wt% and at most about 15 wt% cross-linked polyvinylpyrrolidone; at least about 0.5 wt% and at most about 2.5 wt% sodium lauryl sulfate; at least about 5 wt% and at most about 10 wt% calcium hydrogen phosphate dihydrate; and at least about 0.5 wt% and at most about 2 wt% sodium stearyl fumarate, and optionally, a coating such as a film coating.

[0029] In preferred embodiments of the invention, the tablet consists of at least about 20 wt% and at most about 33 wt% alvelestat tosylate; at least about 50 wt% and at most about 62 wt% microcrystalline cellulose (MCC); at least about 4.5 wt% and at most about 11 wt% cross-linked polyvinylpyrrolidone (PVPcI); at least about 1.1 wt% and at most about 2.2 wt% sodium lauryl sulfate (SLS); at least about 5 wt% and at most about 10 wt% calcium hydrogen phosphate dihydrate (DCP); and at least about 0.5 wt% and at most about 2 wt% sodium stearyl fumarate (SSF), and optionally, a coating such as a film coating.

[0030] In one embodiment, the tablet providing an amount of 120 mg of alvelestat free base consists of about 158 mg alvelestat tosylate, about 320 mg MCC, about 60 mg PVPcI, about 12 mg SLS, about 41 mg DCP, about 9 mg SSF, such that the total core weight of the tablet is about 600 mg, and optionally, a coating such as a film coating.

[0031] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79 mg alvelestat tosylate, about 160 mg MCC, about 30 mg PVPcI,about 6 mg SLS, about 20 mg DCP, and about 5 mg SSF, such that the total core weight of the tablet is about 300 mg, and optionally, a coating such as a film coating.

[0032] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79 mg alvelestat tosylate, about 240 mg MCC, about 40 mg PVPcI, about 8 mg SLS, about 27 mg DCP, and about 6 mg SSF, such that the total core weight of the tablet is about 400 mg, and optionally, a coating such as a film coating.

[0033] In one embodiment, the tablet providing an amount of 120 mg of alvelestat free base consists of about 158 mg alvelestat tosylate, about 320 mg MCC, wherein about 42 mg MCC is provided extragranularly and about 278 mg MCC is provided intragranularly, about 60 mg PVPcI, wherein about 18 mg PVPcI is provided extragranularly and about 42 mg PVPcI is provided intragranularly, about 12 mg SLS, about 41 mg DCP, about 9 mg SSF, wherein about 3 mg SSF is provided extragranularly and about 6 mg SSF is provided intragranularly, such that the total core weight of the tablet is about 600 mg, and optionally, a coating such as a film coating.

[0034] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79 mg alvelestat tosylate, about 160 mg MCC, wherein about 21 mg MCC is provided extragranularly and about 139 mg MCC is provided intragranularly, about 30 mg PVPcI, wherein about 9 mg PVPcI is provided extragranularly and about 21 mg PVPcI is provided intragranularly, about 6 mg SLS, about 20 mg DCP, and about 5 mg SSF, wherein about 1.5 mg SSF is provided extragranularly and about 3 mg SSF is provided intragranularly, such that the total core weight of the tablet is about 300 mg, and optionally, a coating such as a film coating.

[0035] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79 mg alvelestat tosylate, about 240 mg MCC, wherein about 28 mg MCC is provided extragranularly and about 212 mg MCC is provided intragranularly, about 40 mg PVPcI, wherein about 12 mg PVPcI is provided extragranularly and about 28 mg PVPcI is provided intragranularly, about 8 mg SLS, about 27 mg DCP, and about 6 mg SSF, wherein about 2 mg SSF is provided extragranularly and about 4 mg SSF is provided intragranularly, such that the total core weight of the tablet is about 400 mg, and optionally, a coating such as a film coating.

[0036] BRIEF DESCRIPTION OF THE DRAWINGS

[0037] FIG 1A: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for different capsules containing different amounts of alvelestat tosylate.

[0038] FIG 1B: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for different tablets containing different amounts of alvelestat tosylate.

[0039] FIG 2: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for different tablets of Formula A (as described in Table 2), wherein the tablets contain alvelestat tosylate that has been manufactured in Batches A-H.

[0040] FIG 3: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for tablets according to Formulae A-C (as described in Tables 2 and 6), and for 4 of the tablets of Formula A.

[0041] Fig 4A: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for tablets according to Formula D and Formula E (as described in Table 7).

[0042] Fig 4B: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for tablets according to Formulae A, D and E (as described in Tables 2 and 7). Two batches of tablets used for the production of tablets according to Formula A have been shown (a and b).

[0043] Fig 5: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for uncoated tablets according to Formula E (as described in Table 7). Three batches of tablets used for the production of tablets according to Formula A have been shown (X, Y and Z).

[0044] Fig 6A: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for tablets according to Formula G and Formula H (as described in Table 10).

[0045] Fig 6B: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for tablets according to Formulae A, G and H (as described in Tables 2 and 10). Two batches of tablets used for the production of tablets according to Formula A have been shown (a and b).

[0046] Fig 7A: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for coated tablets according to Formula H (as described in Table 10) at different pHs.

[0047] Fig 7B: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for uncoated and coated tablets according to Formula E (as described in Table 7) at different pHs.

[0048] Fig 7C: This graph shows dissolution data (as a percentage of ‘label claim’ (LC)) against time for uncoated and coated tablets according to Formula I (as described in Table 12) at different pHs.

[0049] DETAILED DESCRIPTION

[0050] The description below is made with the understanding that the present disclosure is to be considered as an exemplification of the claimed subject matter and is not intended to limit the appended claims to the specific embodiments illustrated. The present disclosure provides reference to various embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the present disclosure. The headings used throughout this disclosure are provided for convenience and are not to be construed to limit the claims in any way. Embodiments illustrated under any heading may be combined with embodiments illustrated under any other heading.Definitions

[0051] Unless the context requires otherwise, throughout the present specification and claims, the word "comprise" and variations thereof, such as, "comprises" and "comprising" are to be construed in an open, inclusive sense, i.e. as "including, but not limited to". The term “consist of” and variations thereof, such as “consists of” and “consisting of’ are to be construed in a closed sense. For the avoidance of doubt, the open interpretations of the term ’’comprise” (and variations thereof) include within them the closed interpretations given by “consisting of” (and variations thereof).

[0052] Also herein, the recitations of numerical ranges by endpoints include all numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.).

[0053] As used herein, the term "about" means that a degree of variation is allowed at the recited value. For example, ± 10%, ± 5%, or ±1 of the recited value.

[0054] As used herein, “treatment” or “treating” is an approach for obtaining beneficial or desired results. For purposes of the present invention, beneficial or desired results include, but are not limited to, alleviation of a symptom and / or diminishment of the extent of a symptom associated with a disease or condition. “Treatment” or “treating” includes one or more of the following: a) inhibiting the disease or condition (e.g., decreasing one or more symptoms resulting from the disease or condition, and / or diminishing the extent of the disease or condition); b) slowing or arresting the development of one or more symptoms associated with the disease or condition (e.g., stabilizing the disease or condition, delaying the worsening or progression of the disease or condition); and c) relieving the disease or condition, e.g., causing the regression of clinical symptoms,ameliorating the disease state, delaying the progression of the disease, increasing the quality of life, and / or prolonging survival.

[0055] As used herein, "prevention" or "preventing" refers to a regimen that protects against the onset of the disease or disorder such that the clinical symptoms of the disease do not develop. Thus, "prevention" relates to administration of a therapy (e.g., administration of a therapeutic substance) to a subject before signs of the disease are detectable in the subject. The subject may be an individual at risk of developing the disease or disorder, such as an individual who has one or more risk factors known to be associated with development or onset of the disease or disorder.

[0056] As used herein, the term “therapeutically effective amount” or “effective amount” refers to an amount that is effective to elicit the desired biological or medical response, including the amount of a compound that, when administered to a subject for treating a disease, is sufficient to effect such treatment for the disease. The effective amount will vary depending on the particular compound, and characteristics of the subject to be treated, such as age, weight, etc. The effective amount can include a range of amounts. As is understood in the art, an effective amount may be in one or more doses, i.e. , a single dose or multiple doses may be required to achieve the desired treatment endpoint.

[0057] The term "solvate" is used herein to describe a molecular complex comprising the compound of the invention and a one or more pharmaceutically acceptable solvent molecules, for example, ethanol or water.

[0058] The term "hydrate" is employed when the solvent is water and for the avoidance of any doubt, the term "hydrate" is encompassed by the term "solvate".

[0059] The term “pharmaceutically acceptable salt” means a physiologically or toxicologically tolerable salt and includes, when appropriate, pharmaceutically acceptable base addition salts and pharmaceutically acceptable acid addition salts. For a review of suitable salts, see “Handbook of Pharmaceutical Salts: Properties, Selection and Use” by Stahl and Wermuth (Wiley-VCH, 2011).

[0060] “Pharmaceutically acceptable" or "physiologically acceptable" refer to compounds, salts, compositions, dosage forms etc. which are suitable for pharmaceutical use.

[0061] All documents referenced herein are each incorporated by reference in their entirety for all purposes.Pharmaceutical formulations

[0062] The following embodiments of the invention may be combined with each other to form further embodiments of the invention. Any explicit combinations described below do not preclude the combinations of other embodiments which have not been explicitly recited or exemplified.

[0063] The pharmaceutical formulations of the invention are tablets comprising alvelestat or a pharmaceutically acceptable salt thereof. Typically, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 10 wt% of alvelestat free base. Typically, the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to about 60 mg or 120 mg of alvelestat free base, for example 120 mg.Alvelestat

[0064] Alvelestat is a neutrophil elastase inhibitor disclosed in WO 2005026123, incorporated by reference in its entirety.

[0065] In the tablets of the invention, alvelestat may be provided as the free base or as a pharmaceutically acceptable salt thereof. Pharmaceutically acceptable salts of alvelestat are also disclosed in WO 2005026123 and WO2010094964, incorporated by reference in its entirety as mentioned above.

[0066] Typically, alvelestat is provided as the free base or as alvelestat tosylate, preferably as alvelestat tosylate. A tosylate salt may also be referred to as a 4- methylbenzenesulfonate salt.

[0067] Alvelestat tosylate is disclosed in WO 2010094964, incorporated by reference in its entirety. In particular, alvelestat tosylate may be used in the form of the crystalline Form A disclosed in WO 2010094964 in the tablets of the invention. Alvelestat tosylate Form A has an X-ray powder diffraction pattern measured using CuKaradiation with at least one specific peak at 20 = about 5.1, 7.3, 8.9, 17.0 or 17.8, preferably with specific peaks at 20 = about 5.1, 7.3, 8.9, 17.0 and 17.8. All XRPD peaks described herein may have a measurement error of ±0.5° 20.Tablets

[0068] The tablets of the invention comprise alvelestat or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 10 wt% of alvelestat free base.

[0069] Thus, the amount may be at least about 11 wt%, at least about 12 wt%, at least about 13 wt%, at least about 14% or preferably at least about 15 wt%.

[0070] The amount of alvelestat or a pharmaceutically acceptable salt thereof is not particularly limited, but may in some embodiments be at most about 40 wt%. Thus, the amount may be at most about 35 wt%, at most about 32 wt%, at most about 30 wt%, at most about 28 wt%, at most about 25 wt%, at most about 22 wt%, or preferably at most about 20 wt%.

[0071] Thus, a tablet disclosed herein may comprise an amount of alvelestat or a pharmaceutically acceptable salt thereof corresponding to at least about 15 wt% of alvelestat free base and at most about 40 wt% of alvelestat free base, in particular at least about 15 wt% of alvelestat free base and at most about 25 wt% of alvelestat free base. Preferably, a tablet disclosed herein comprises an amount of alvelestat or a pharmaceutically acceptable salt thereof corresponding to at least about 15 wt% of alvelestat free base and at most about 20 wt% of alvelestat free base.

[0072] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base.

[0073] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base.Weight of tablet

[0074] The weight of the tablet may be adjusted accordingly, in order to make a tablet with the desired amount of alvelestat. The “tablet core weight” as calculated herein is the sum total of the weight of alvelestat or pharmaceutically acceptable salt thereof, and any excipients except the coating.

[0075] In some embodiments, the tablet core weight is between about 500 mg to 1200 mg.

[0076] In some embodiments, the tablet core weight is between about 300 mg to 600 mg.

[0077] In some embodiments, the tablet core weight is about 300 mg.

[0078] In some embodiments, the tablet core weight is about 400 mg.

[0079] In some embodiments, the tablet core weight is about 600 mg.

[0080] For example, a tablet of the invention providing an amount of alvelestat or a pharmaceutically acceptable salt thereof corresponding to 120 mg of alvelestat free base advantageously has a tablet core weight of about 600 mg. In another example, a tablet of the invention providing an amount of alvelestat or a pharmaceutically acceptable salt thereof corresponding to 60 mg of alvelestat free base advantageously has a tablet core weight of about 300 mg. In yet another example, a tablet of the invention providing an amount of alvelestat or a pharmaceutically acceptable salt thereof corresponding to 60 mg of alvelestat free base advantageously has a tablet core weight of about 400 mg.Dosages

[0081] Typically, a tablet disclosed herein comprises an amount of alvelestat or pharmaceutically acceptable salt thereof corresponding to at least about 60 mg and at most about 120 mg of alvelestat free base. Thus, in some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof, wherein the amount of alvelestat or a pharmaceutically acceptable salt thereof corresponds to about 60 mg, about 80 mg, or about 120 mg of alvelestat free base. Preferably, the amount corresponds to 60 mg or 120 mg of alvelestat free base.

[0082] In some embodiments, the tablet comprises an amount of alvelestat or a pharmaceutically acceptable salt thereof corresponding to about 20 wt% of alvelestat free base, wherein the amount of alvelestat or a pharmaceutically acceptable salt thereof corresponds to about 120 mg of alvelestat free base.

[0083] In some embodiments, the tablet comprises an amount of alvelestat or a pharmaceutically acceptable salt thereof corresponding to about 20 wt% of alvelestat free base, wherein the amount of alvelestat or a pharmaceutically acceptable salt thereof corresponds to about 60 mg of alvelestat free base.

[0084] In some embodiments, the tablet comprises an amount of alvelestat or a pharmaceutically acceptable salt thereof corresponding to about 15 wt% of alvelestat freebase, wherein the amount of alvelestat or a pharmaceutically acceptable salt thereof corresponds to about 60 mg of alvelestat free base.

[0085] As noted above, in some embodiments, the tablet comprises a pharmaceutically acceptable salt of alvelestat. The present invention includes compounds of formula (I) in the form of salts, in particular acid addition salts. Suitable salts include those formed with both organic and inorganic acids. Such acid addition salts will normally be pharmaceutically acceptable although salts of non-pharmaceutically acceptable acids may be of utility in the preparation and purification of the compound in question. Thus, preferred salts include those formed from hydrochloric, hydrobromic, sulphuric, phosphoric, citric, tartaric, lactic, pyruvic, acetic, succinic, fumaric, maleic, methanesulphonic and benzenesulphonic acids. The pharmaceutically acceptable salt may be alvelestat tosylate or alvelestat mesylate. Preferably, the pharmaceutically acceptable salt of alvelestat is alvelestat tosylate.

[0086] Amounts and drug loads of alvelestat are typically provided herein as corresponding amounts and drug loads of alvelestat free base. The amount of pharmaceutically acceptable salt that corresponds to a certain amount of the free base can easily be calculated by taking into account the molecular mass of the counterion(s). For example, about 158 mg of alvelestat tosylate provides about 120 mg of alvelestat free base. About 79 mg of alvelestat tosylate provides about 60 mg of alvelestat free base. About 13.2 wt% of alvelestat tosylate corresponds to about 10 wt% of alvelestat free base. The same calculations can be performed to determine the corresponding amounts for other amounts and salts referred to herein.

[0087] Thus, preferred tablets of the invention comprise about 158 mg of alvelestat tosylate. Other preferred tablets of the invention comprise about 79 mg of alvelestat tosylate.

[0088] Accordingly, the invention also provides tablets comprising alvelestat tosylate, and one or more pharmaceutically acceptable excipients, wherein the tablet comprises at least about 13.2 wt% of alvelestat tosylate. In particular, the tablet comprises at least about 19.7 wt% of alvelestat tosylate and at most about 52.6 wt% of alvelestat tosylate, in particular at least about 19.7 wt% of alvelestat tosylate and at most about 32.9 wt% of alvelestat tosylate.

[0089] The invention also provides tablets comprising alvelestat tosylate, and one or more pharmaceutically acceptable excipients, wherein the tablet comprises about 26.3 wt% alvelestat tosylate. In preferred embodiments, these tablets comprise about 158 mg or about 79 mg alvelestat tosylate, more preferably about 158 mg.

[0090] The invention also provides tablets comprising alvelestat tosylate, and one or more pharmaceutically acceptable excipients, wherein the tablet comprises about 19.7 wt% alvelestat tosylate. In preferred embodiments, these tablets comprise about 158 mg or about 79 mg alvelestat tosylate, more preferably about 79 mg.Coatings

[0091] The tablets of the invention may be uncoated or coated.

[0092] In some embodiments, the tablets disclosed herein are uncoated. An uncoated tablet consists of an amount of alvelestat or a pharmaceutically acceptable salt thereof and any excipients other than a coating. For any uncoated tablet disclosed or provided as an embodiment herein, a coated tablet, the same in all respects except for the addition of a coating, is also disclosed or provided as an embodiment.

[0093] Typically, however, the tablets of the invention are coated. Suitable coatings include film coatings. Provision of a film coating may result in a better dissolution profile for a tablet.

[0094] Film coatings are known in the art and can be composed of hydrophilic polymer materials. Though the water soluble material included in the film coating of the present disclosure may include a single polymer material, it may also be formed using a mixture of more than one polymer. The coating may be clear, white or colored.

[0095] Suitable film coatings include, but are not limited to, polysaccharide materials, such as hydroxypropyl methyl cellulose (HPMC), methylcellulose, hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), poly(vinylalcohol-co-ethylene glycol) and other water soluble polymers. In some embodiments, the film coating is Opadry. In some embodiments, the film coating is Opadry 03F230007 peach, comprising 71.1 %w / w Hydroxy Propyl Methylcellulose (Hypromellose), 10.0 %w / w titanium dioxide, 17.8 %w / w Polyethylene glycol (Macrogol / PEG) MACROGOL 6000 or MW 8000, 0.92 %w / w iron oxide yellow, and 0.21 %w / w iron oxide red, wherein the w / w% are expressed as % weight of component relative to the total weight of the coating. In some embodiments, the film coating is Opadry 03B28460 white, comprising 65.3 %w / w Hydroxy Propyl Methylcellulose (Hypromellose), 21.3 %w / w titanium dioxide, and 13.3 %w / w Polyethylene glycol (Macrogol / PEG) MW 6000 grade, wherein the w / w% are expressed as % weight of component relative to the total weight of the coating. In some embodiments, the powder is dispersed in purified water before the start of the coating process.

[0096] The amount of coating will generally be between about 2-6% of the tablet core’s weight, preferably 4 wt%. Unless specifically stated otherwise, where the tablet is coated, it is to be understood that a reference to wt% is calculated with respect to the tablet core weight. The “tablet core weight” as calculated herein is the sum total of the weight of alvelestat or pharmaceutically acceptable salt thereof, and any excipients of the uncoated tablet.Excipients

[0097] Tablets will typically include one or more excipients. Excipients are constituents of a tablet other than the active substance.

[0098] Excipients should be compatible with the other ingredients of the formulation and physiologically innocuous to the recipient thereof. Examples of suitable excipients are well known to the person skilled in the art of tablet formulation and may be found e.g. in Handbook of Pharmaceutical Excipients (eds. Rowe, Sheskey & Quinn), 6th edition 2009. Excipients include, for example, adjuvants, diluents, fillers, disintegrants, lubricants, surfactants, basifying agents, solubilisers, glidants, binders, preservatives, surface active agents, dispersing agents, sweetening agents, flavoring agents, coloring agents, preserving agents and the like.

[0099] Where tablets of the invention are manufactured via granulation, components of the tablets disclosed herein may be provided intragranularly or extragranularly. In the tablet forms disclosed herein, portions of any excipients may be provided intragranularly or extragranularly.Filler

[0100] In some embodiments, the tablet may comprise one or more fillers (also known as diluents).

[0101] In some embodiments, an amount of one or more fillers is provided intragranularly. In some embodiments, an amount of one or more fillers is provided extragranularly. In some embodiments, an amount of one or more fillers is provided intragranularly and an amount of the one or more fillers is provided extragranularly.

[0102] In some embodiments, the filler may comprise one or more than one of the following: lactose or other polyols, including lactose anhydrous, sucrose, glucose, saccharose, sorbitol, mannitol, dibasic calcium phosphate (dicalcium phosphate) including hydrated forms such as calcium hydrogen phosphate dihydrate, and anhydrous forms,calcium sulphate; a starch, for example, potato starch, corn (maize) starch or amylopectin; maltodextrins, a cellulose derivative such as microcrystalline cellulose (MCC) or silicified microcrystalline cellulose (SMCC), Hypromellose, and the like. Examples of dibasic calcium phosphate dihydrate products are Calipharm D (from InnoPhos), ICL D (from ICL Performance Products), Calstar (FMC Biopolymer), Di-Cafos (Chemische Fabrik Budenheim), DI-TAB (Innophos) and Emcompress (JRS Pharma LP). Examples of dibasic calcium phosphate anhydrate are ICL A (from ICL Performance Products), Fuji Calin (from Fuji Chemicals), A-TAB (Innophos), Di-Cafos AN (Chemische Fabrik Budenheim) and Emcompress Anhydrous (JRS Pharma LP). Examples of mannitol products is Pearlitol DC 300 and Pearlitol SD200 (manufactured by Roquette). An example of a lactose product is Pharmatose DCL 15 (manufactured by DMV).

[0103] In some embodiments, fillers may be used individually or in combination. In some embodiments, the tablet may comprise maize starch. In some embodiments, the tablet may comprise lactose anhydrous and mannitol.

[0104] In some preferred embodiments, the filler comprises MCC. In some preferred embodiments, the filler comprises calcium hydrogen phosphate dihydrate (DCP). In some preferred embodiments, the filler comprises MCC and DCP.Disintegrant

[0105] In some embodiments, the tablet comprises one or more disintegrating agents or disintegrants.

[0106] In some embodiments, an amount of one or more disintegrants is provided intragranularly. In some embodiments, an amount of one or more disintegrants is provided extragranularly. In some embodiments, an amount of one or more disintegrants is provided intragranularly and an amount of the one or more disintegrants is provided extragranularly.

[0107] Disintegrating agents or disintegrants include for example, carmellose calcium, carboxymethyl starch sodium, croscarmellose sodium, polyvinylpyrrolidone (PVP), crospovidone (crosslinked polyvinylpyrrolidone, PVPcI), celluloses such as MCC or low substituted hydroxypropyl cellulose; starches such as pre-gelatinized starch, hydroxypropyl starch; alginate and the like.

[0108] Disintegrants include super-disintegrants. Super-disintegrants include for example crospovidone (PVPcI), croscarmellose sodium, sodium starch glycolate, calcium carboxymethylcellulose, calcium cellulose glycolate, carmellose calcium, chitosan hydrochloride, magnesium aluminum silicate.

[0109] In some embodiments, an amount of one or more super-disintegrants is provided intragranularly. In some embodiments, an amount of one or more super- disintegrants is provided extragranularly. In some embodiments, an amount of one or more super-disintegrants is provided intragranularly and an amount of the one or more super- disintegrants is provided extragranularly.

[0110] The name crospovidone is used interchangeably with crosslinked polyvinylpyrrolidone and is abbreviated PVPcI. This is distinguished from non-crosslinked polyvinylpyrrolidone, which is referred to as PVP.

[0111] In some embodiments, disintegrants, including super-disintegrants, may be used individually or in combination.

[0112] In some preferred embodiments, the disintegrant comprises MCC. In some preferred embodiments, the disintegrant comprises crospovidone (PVPcI). In some preferred embodiments, the disintegrant comprises MCC and PVPcI.Lubricant

[0113] In some embodiments, the tablet comprises one or more lubricants.

[0114] In some embodiments, an amount of one or more lubricants is provided intragranularly. In some embodiments, an amount of one or more lubricants is provided extragranularly. In some embodiments, an amount of one or more lubricants is provided intragranularly and an amount of the one or more lubricants is provided extragranularly.

[0115] Lubricants include magnesium stearate, calcium stearate, sucrose esters of fatty acids, metallic salts of fatty acids, sodium lauryl sulfate, sodium stearyl fumarate (SSF), stearic acid, glycerin fatty acid esters, fatty acids, talc, PEG 6000, glycerin behenate, magnesium lauryl sulphate, polyethyleneglycol, wax, paraffin and the like.

[0116] In some embodiments, lubricants may be used individually or in combination. For example, a combination of sodium lauryl sulfate and magnesium stearate may be used.

[0117] In some preferred embodiments, the lubricant comprises sodium lauryl sulfate. In some preferred embodiments, the lubricant comprises sodium stearyl fumarate. In more preferred embodiments, the lubricant comprises sodium lauryl sulfate and sodium stearyl fumarate.Surfactant

[0118] In some embodiments, the tablet comprises one or more surfactants. Surfactants may comprise wetting enhancers.

[0119] Surfactants include sodium lauryl sulfate (SLS), polysorbate 80, hydrogenated oil, polyoxyethylene(160)polyoxypropylene(30)glycol, and the like.

[0120] In some embodiments, surfactants may be used individually or in combination.

[0121] In preferred embodiments, the surfactant comprises SLS.Binder

[0122] Tablets as disclosed herein may optionally further comprise a binder, for example, hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), polyvinylpyrrolidone (PVP) or gelatine

[0123] In some embodiments, binders may be used individually or in combination.Tablet components

[0124] In some embodiments, the tablet comprises one or more fillers and one or more disintegrants.

[0125] In some embodiments, the tablet comprises one or more fillers and one or more lubricants.

[0126] In some embodiments, the tablet comprises one or more fillers and one or more surfactants.

[0127] In some embodiments, the tablet comprises one or more disintegrants and one or more lubricants.

[0128] In some embodiments, the tablet comprises one or more disintegrants and one or more surfactants.

[0129] In some embodiments, the tablet comprises one or more lubricants and one or more surfactants.

[0130] In some embodiments, the tablet comprises one or more fillers, one or more disintegrants, and one or more lubricants.

[0131] In some embodiments, the tablet comprises one or more fillers, one or more disintegrants, and one or more surfactants.

[0132] In some embodiments, the tablet comprises one or more fillers, one or more lubricants, and one or more surfactants.

[0133] In some embodiments, the tablet comprises one or more disintegrants, one or more lubricants, and one or more surfactants.

[0134] In some embodiments, the tablet comprises one or more fillers, one or more disintegrants, one or more lubricants, and one or more surfactants.Amounts of excipientsFillers

[0135] In some embodiments, the tablet comprises one or more fillers in an amount of about 40 wt% to about 80 wt%, or about 40 wt% to about 70 wt%, about 50 wt% to about 70 wt%, about 50 wt% to about 60 wt%, about 55 wt% to about 70%, or about 60 wt% to about 70 wt%. In some preferred embodiments, a tablet comprises one or more fillers in an amount of about 50 wt% to about 60 wt%. In some preferred embodiments, a tablet comprises one or more fillers in an amount of about 60 wt% to about 70 wt%.Disintegrants

[0136] In some embodiments, the tablet comprises one or more disintegrants in an amount of about 40 wt% to about 80 wt%, or about 50 wt% to about 70 wt%, or about 60 wt% to about 70 wt%. In some preferred embodiments, a tablet comprises one or more disintegrants in an amount of about 50 wt% to about 60 wt%. In some preferred embodiments, a tablet comprises one or more disintegrants in an amount of about 60 wt% to about 70 wt%.

[0137] In some embodiments, the tablet comprises one or more super-disintegrants in an amount of about 3 wt% to about 15 wt%, preferably about 4.5 wt% to about 11 wt%, more preferably about 10 wt%.

[0138] In some embodiments, the tablet comprises one or more disintegrants that are not super-disintegrants in an amount of about 50 wt% to about 60 wt%, and further comprises one or more super-disintegrants in an amount of about 3 wt% to about 15 wt% or about 4.5 wt% to about 11 wt%, or about 10 wt%.Lubricants

[0139] In some embodiments, the tablet comprises one or more lubricants in an amount of about 0.1 wt% to about 5 wt%, or about 0.5 wt% to about 3.5 wt%, or about 0.5 wt% to about 2.5 wt%, or about 1 wt% to about 2 wt%. In some preferred embodiments, a tablet comprises one or more lubricants in an amount of about 1 wt% to about 2 wt%, or about 2 wt% to about 4 wt%.Surfactants

[0140] In some embodiments, the tablet comprises one or more surfactants in an amount of about 0.1 wt% to about 4 wt%, about 0.5 wt% to about 2.5 wt%, or about 1.1 wt% to about 2.2 wt%, or about 1.5 wt% to about 2.5 wt%. In some preferred embodiments, a tablet comprises one or more surfactants in an amount of about 1 wt% to about 2 wt%.Tablet component compositions

[0141] Provided below are non-limiting embodiments of the invention defining amounts of components and types of excipients that may be seen in tablets according to the invention.

[0142] In some embodiments, the tablet comprises one or more fillers and one or more disintegrants in a total amount of about 40 wt% to about 80 wt%.

[0143] In some embodiments, the tablet comprises one or more fillers in an amount of about 40 wt% to about 80 wt% and one or more surfactants in an amount of about 0.1 wt% to about 4 wt%.

[0144] In some embodiments, the tablet comprises one or more fillers in an amount of about 40 wt% to about 80 wt%, and one or more lubricants in an amount of about 0.1 wt% to about 5 wt%.

[0145] In some embodiments, the tablet comprises one or more disintegrants in an amount of about 40 wt% to about 80 wt% and one or more surfactants in an amount of about 0.1 wt% to about 4 wt%.

[0146] In some embodiments, the tablet comprises one or more disintegrants in an amount of about 40 wt% to about 80 wt% and one or more lubricants in an amount of about 0.1 wt% to about 5 wt%.

[0147] In some embodiments, the tablet comprises one or more surfactants and one or more lubricants in a total amount of about 1 wt% to about 5 wt%.

[0148] In some embodiments, the tablet comprises one or more fillers in an amount of about 40 wt% to about 80 wt%, and one or more surfactants and one or more lubricants in a total amount of about 1 wt% to about 5 wt%.

[0149] In some embodiments, the tablet comprises one or more disintegrants in an amount of about 40 wt% to about 80 wt%, and one or more surfactants and one or more lubricants in a total amount of about 1 wt% to about 5 wt%.

[0150] In some embodiments, the tablet comprises one or more fillers and one or more disintegrants in a total amount of about 40 wt% to about 80 wt%, and one or more surfactants in an amount of about 0.1 wt% to about 4 wt%.

[0151] In some embodiments, the tablet comprises one or more fillers and one or more disintegrants in a total amount of about 40 wt% to about 80 wt%, and one or more lubricants in an amount of about 0.1 wt% to about 5 wt%.

[0152] In some embodiments, the tablet comprises one or more fillers and one or more disintegrants in a total amount of about 40 wt% to about 80 wt%, and one or more surfactants and one or more lubricants in a total amount of about 1 wt% to about 5 wt%.

[0153] In some embodiments, the tablet comprises one or more fillers and one or more disintegrants in a total amount of about 65 wt% to about 80 wt%.

[0154] In some embodiments, the tablet comprises one or more fillers in an amount of about 55 wt% to about 70 wt% and one or more surfactants in an amount of about 1 wt% to about 2 wt%.

[0155] In some embodiments, the tablet comprises one or more fillers in an amount of about 55 wt% to about 70 wt% and one or more lubricants in an amount of about 1.5 wt% to about 3.5 wt%.

[0156] In some embodiments, the tablet comprises one or more disintegrants in an amount of about 60 wt% to about 70 wt% and one or more surfactants in an amount of about 1 wt% to about 2 wt%.

[0157] In some embodiments, the tablet comprises one or more disintegrants in an amount of about 60 wt% to about 70 wt% and one or more lubricants in an amount of about 1 wt% to about 2 wt%, or about 2 wt% to about 4 wt%.

[0158] In some embodiments, the tablet comprises one or more surfactants and one or more lubricants in a total amount of about 2 wt% to about 4 wt%.

[0159] In some embodiments, the tablet comprises one or more fillers in an amount of about 55 wt% to about 70 wt%, and one or more surfactants and one or more lubricants in a total amount of about 2 wt% to about 4 wt%.

[0160] In some embodiments, the tablet comprises one or more disintegrants in an amount of about 55 wt% to about 70 wt%, and one or more surfactants and one or more lubricants in a total amount of about 2 wt% to about 4 wt%.

[0161] In some embodiments, the tablet comprises one or more fillers and one or more disintegrants in a total amount of about 65 wt% to about 80 wt%, and one or more surfactants and one or more lubricants in a total amount of about 2 wt% to about 4 wt%.

[0162] In some embodiments, the tablet comprises one or more fillers in an amount of about 40 wt% to about 70 wt%, and one or more super-disintegrants in an amount of about 3 wt% to about 15 wt%.

[0163] In some embodiments, the tablet comprises one or more fillers in an amount of about 55 wt% to about 70 wt%, and one or more super-disintegrants in an amount of about 9 wt% to about 11 wt%.

[0164] In some embodiments, the tablet comprises one or more fillers in an amount of about 55 wt% to about 70 wt%, one or more super-disintegrants in an amount of about 9 wt% to about 11 wt%, and one or more surfactants and one or more lubricants in a total amount of about 2 wt% to about 4 wt%.Exemplary excipients

[0165] Further detail is provided below relating to exemplary excipients which may be used in the composition of the tablets according to the invention disclosed herein. The subject-matter of the invention is not restricted to these components and other components as described above may also be used.Microcrystalline cellulose (MCC)

[0166] In some embodiments, a tablet disclosed herein comprises one or more cellulose derivatives. Examples of cellulose derivatives such as microcrystalline cellulose, include Avicel PH 101, PH 102, PH 102 SCG, PH200, PH301 , PH302, and PH-F20, Avicel RC-A591NF. An example of silicified microcrystalline cellulose products is ProSolv 90 HD, a mixture of MCC and colloidal silicon dioxide (manufactured by JRS Pharma).

[0167] In some embodiments, the tablet comprises microcrystalline cellulose (MCC). MCC may act as a filler and / or a disintegrant.

[0168] In some embodiments, the tablet comprises at least about 40 wt%, at least about 45 wt%, or at least about 50 wt% MCC. Preferably, a tablet disclosed herein comprises at least about 50 wt% MCC.

[0169] In some embodiments, the tablet comprises at most about 75 wt%, at most about 70 wt%, at most about 65 wt%, or at most about 62 wt% MCC. Preferably, a tablet disclosed herein comprises at most about 62 wt% MCC.

[0170] In some embodiments, the tablet comprises at least about 40 wt% MCC and at most about 75 wt% MCC, or at least about 40 wt% MCC and at most about 70 wt% MCC, or at least about 45 wt% MCC and at most about 70 wt% MCC, or at least about 45 wt% MCC and at most about 65 wt% MCC or at least about 50 wt% MCC and at most about 65 wt% MCC, or at least about 50 wt% MCC and at most about 62 wt% MCC.

[0171] Preferably, a tablet disclosed herein comprises at least about 40 wt% MCC and at most about 70 wt% MCC. More preferably, the tablet may comprise at least about 45 wt% MCC and at most about 65 wt% MCC. More preferably still, the tablet may comprise at least about 50 wt% MCC and at most about 62 wt% MCC.

[0172] In some embodiments, the tablet comprises about 53 wt% MCC. A tablet disclosed herein may comprise about 53.4 wt% MCC.

[0173] In some embodiments, the tablet comprises about 59 wt% MCC. A tablet disclosed herein may comprise about 58.6 wt% MCC.

[0174] In some embodiments, the tablet comprises about 60 wt% MCC. A tablet disclosed herein may comprise about 59.9 wt% MCC or about 60.0 wt% MCC.

[0175] In some embodiments, an amount of MCC may be provided intragranularly. In some embodiments, an amount of MCC may be provided extragranularly. In some embodiments, an amount of MCC may be provided intragranularly and an amount of MCC may be provided extragranularly.

[0176] In some embodiments, about 5 wt% to about 10 wt% MCC is provided extragranularly. In some embodiments, about 40 wt% to about 55 wt% MCC is providedintragranularly. In some embodiments, about 5 wt% to about 10 wt% MCC is provided extragranularly and about 40 wt% to about 55 wt% MCC is provided intragranularly. In some embodiments, the tablet comprises about 45 wt% MCC to about 65 wt% MCC, and about 5 wt% to about 10 wt% MCC is provided extragranularly and about 40 wt% to about 55 wt% MCC is provided intragranularly.

[0177] In some embodiments, about 7% MCC is provided extragranularly. In some embodiments, about 46 wt% MCC is provided intragranularly. In some embodiments, about 7 wt% MCC is provided extragranularly and about 46 wt% MCC is provided intragranularly. In some embodiments, the tablet comprises about 53 wt% MCC, and about 7 wt% MCC is provided extragranularly and about 46 wt% MCC is provided intragranularly.

[0178] In some embodiments, the tablet comprises about 53.4 wt% MCC, and about 7.0 wt% MCC is provided extragranularly and about 46.4 wt% MCC is provided intragranularly.

[0179] In some embodiments, about 7% MCC is provided extragranularly. In some embodiments, about 53 wt% MCC is provided intragranularly. In some embodiments, about 7 wt% MCC is provided extragranularly and about 53 wt% MCC is provided intragranularly. In some embodiments, the tablet comprises about 60 wt% MCC, and about 7 wt% MCC is provided extragranularly and about 53 wt% MCC is provided intragranularly.

[0180] In some embodiments, the tablet comprises about 59.9 or about 60.0 wt% MCC, and about 7.0 wt% MCC is provided extragranularly and about 52.9 or about 53.0 wt% MCC is provided intragranularly.Crospovidone / Crosslinked polyvinylpyrrolidone (PVPcI)

[0181] As above, crospovidone is used interchangeably with crosslinked polyvinylpyrrolidone and is abbreviated PVPcI. This is distinguished from non-crosslinked polyvinylpyrrolidone, which is referred to as PVP.

[0182] In some embodiments, the tablet comprises crospovidone (crosslinked polyvinylpyrrolidone, PVPcI). PVPcI acts as a super-disintegrant. In the tablet compositions proposed herein, the use of PVPcI may provide improved dissolution properties. Without wishing to be bound by theory, PVPcI may be a particularly effective super-disintegrant due to a combined effect of swelling, enhancing wettability, and wicking via capillary action.

[0183] In some embodiments, the tablet comprises an amount of PVPcI wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is from about 1:2 to about 1 :20, or is from about 1 :3 to about 1 :15, or is from about 1 :4 to about 1 :12, oris from about 1 :5 to 1 :6. In some embodiments, the ratio is about 1 :5, about 1 .6, or about 1 :11. The ratio of these components may contribute to the provision of tablets with favourable dissolution properties while maintaining processability.

[0184] In some embodiments, the tablet comprises at least about 3 wt% PVPcI, at least about 5 wt% PVPcI, at least about 7 wt% PVPcI, or at least about 9 wt% PVPcI. Preferably, a tablet disclosed herein comprises at least about 9 wt% PVPcI.

[0185] In some embodiments, the tablet comprises at most about 15 wt% PVPcI, at most about 13 wt% PVPcI, or at most about 11 wt% PVPcI. Preferably, a tablet disclosed herein comprises at most about 11 wt% PVPcI.

[0186] In some embodiments, the tablet comprises at least about 3 wt% PVPcI and at most about 15 wt% PVPcI, or at least about 4.5 wt% PVPcI and at most about 13 wt% PVPcI, or at least about 4.5 wt% PVPcI and at most about 11 wt% PVPcI, or at least about 7 wt% PVPcI and at most about 13 wt% PVPcI, or at least about 9 wt% PVPcI and at most about 11 wt% PVPcI.

[0187] A tablet disclosed herein comprises at least about 3 wt% PVPcI and at most about 15 wt% PVPcI. Preferably, a tablet disclosed herein comprises at least about 4.5 wt% PVPcI and at most about 11 wt% PVPcI, or at least about 7 wt% PVPcI and at most about 13 wt% PVPcI. Most preferably, a tablet disclosed herein comprises at least about 9 wt% PVPcI and at most about 11 wt% PVPcI.

[0188] In some preferred embodiments, tablets disclosed herein comprise about 10 wt% PVPcI.

[0189] In some preferred embodiments, tablets disclosed herein comprise about 5 wt% PVPcI, or about 5.4 wt% PVPcI.

[0190] In some embodiments, an amount of PVPcI may be provided intragranularly. In some embodiments, an amount of PVPcI may be provided extragranularly. In some embodiments, an amount of PVPcI may be provided intragranularly and an amount of PVPcI may be provided extragranularly.

[0191] In some embodiments, about 1 wt% to about 4 wt% PVPcI is provided extragranularly. In some embodiments, about 3.5 wt% to about 7 wt% PVPcI is provided intragranularly. In some embodiments, about 1 wt% to about 5 wt% PVPcI is provided extragranularly and about 3.5 wt% to about 7 wt% PVPcI is provided intragranularly. In some embodiments, the tablet comprises about 4.5 wt% to about 11 wt% PVPcI, and about 1 wt% to about 4 wt% PVPcI is provided extragranularly and about 3.5 wt% to about 7 wt% PVPcI is provided intragranularly.

[0192] In some embodiments, about 3% PVPcI is provided extragranularly. In some embodiments, about 7 wt% PVPcI is provided intragranularly. In some embodiments, about 3 wt% PVPcI is provided extragranularly and about 7 wt% PVPcI is provided intragranularly. In some embodiments, the tablet comprises about 10 wt% PVPcI, and about 3 wt% PVPcI is provided extragranularly and about 7 wt% PVPcI is provided intragranularly.

[0193] In some embodiments, the tablet comprises about 10.0 wt% PVPcI, and about 3.0 wt% PVPcI is provided extragranularly and about 7.0 wt% PVPcI is provided intragranularly.Sodium lauryl sulfate (SLS)

[0194] In some embodiments, the tablet comprises sodium lauryl sulfate (SLS). SLS may act as a surfactant, a lubricant, and / or a wetting enhancer. In the tablet compositions proposed herein, the use of SLS may increase the dissolution rate of the tablet.

[0195] In some embodiments, the tablet comprises at least about 0.3 wt%, at least about 0.5, at least about 0.7 wt%, at least about 0.9 wt%, at least about 1.1 wt%, at least about 1.3 wt%, or at least about 1.4 wt% SLS. Preferably, a tablet disclosed herein comprises at least about 1.4 wt% SLS.

[0196] In some embodiments, the tablet comprises at most about 3.0 wt%, at most about 2.5 wt%, at most about 2.2 wt%, or at most about 2.0 wt% SLS. Preferably, a tablet disclosed herein comprises at most about 2 wt% SLS.

[0197] In some embodiments, the tablet comprises at least about 0.3 wt% SLS and at most about 3 wt% SLS, or at least about 0.5 wt% SLS and at most about 2.5 wt% SLS, or at least about 0.7 wt% SLS and at most about 2.2 wt% SLS, or at least about 0.9 wt% SLS and at most about 2.2 wt% SLS, or at least about 1.1 wt% SLS and at most about 2.2 wt% SLS, or at least about 1.4 wt% SLS and at most about 2 wt% SLS.

[0198] Preferably, a tablet disclosed herein comprises at least about 0.5 wt% SLS and at most about 2.5 wt% SLS. More preferably, tablets disclosed herein comprise at least about 1.1 wt% SLS and at most about 2.2 wt% SLS. Most preferably, tablets disclosed herein comprises at least about 1.4 wt% SLS and at most about 2 wt% SLS.

[0199] In some preferred embodiments, a tablet disclosed herein comprises about 2 wt% SLS, or about 2.0 wt% SLS. In some preferred embodiments, a tablet disclosed herein comprises about 1 wt% SLS, or about 1.4 wt% SLS.Calcium hydrogen phosphate dihydrate (DCP)

[0200] In some embodiments, the tablet comprises calcium hydrogen phosphate dihydrate (DCP).

[0201] Calcium hydrogen phosphate dihydrate (CAS# 7789-77-7, EC number 231- 826-1) is synonymous with dibasic calcium phosphate dihydrate and with dicalcium phosphate dihydrate. In some embodiments, DCP is supplied as Calipharm D (from Innophos).

[0202] In some embodiments, an amount of DCP may substitute an amount of MCC to provide further embodiments of tablets according to the invention. In some embodiments, the ratio of the amount of DCP in a tablet to the amount of MCC in the tablet is from about 1 :2 to about 1 :18. Preferably, the ratio of the amount of DCP in a tablet to the amount of MCC in the tablet is from about 1:7 to about 1 :11. More preferably, the ratio of the amount of DCP in a tablet to the amount of MCC in the tablet is from about 1:8 to about 1 :9.

[0203] In some preferred embodiments, the ratio of the amount of DCP in a tablet to the amount of MCC in the tablet is about 1:8. In some preferred embodiments, the ratio of the amount of DCP in a tablet to the amount of MCC in the tablet is about 1 :9.

[0204] In some embodiments, the tablet comprises at least about 3 wt%, at least about 4 wt%, at least about 5 wt%, at least about 6 wt%, at least about 7 wt%, or at least about 8 wt% DCP. Preferably, a tablet disclosed herein comprises at least about 5 wt% DCP.

[0205] In some embodiments, the tablet comprises at most about 7 wt%, at most about 8 wt%, at most about 9 wt%, at most about 10 wt%, at most about 11 wt%, or at most about 12 wt% DCP. Preferably, a tablet disclosed herein comprises at most about 10 wt% DCP.

[0206] In some embodiments, the tablet comprises at least about 3 wt% DCP and at most about 12 wt% DCP, or at least about 5 wt% DCP and at most about 10 wt% DCP, or at least about 6 wt% DCP and at most about 8 wt% DCP, or at least about 6 wt% DCP and at most about 7 wt% DCP.

[0207] Preferably, a tablet disclosed herein comprises at least about 5 wt% DCP and at most about 10 wt% DCP. More preferably, a tablet disclosed herein comprises at least about 6 wt% DCP and at most about 7 wt% DCP. Most preferably, tablets disclosed herein comprise about 7 wt% or about 6.8 wt% DCP.Sodium stearyl fumarate (SSF)

[0208] In some embodiments, the tablet comprises sodium stearyl fumarate (SSF).

[0209] In some embodiments, the tablet comprises at least about 0.1 wt%, at least about 0.5 wt%, at least about 1 wt%, or at least about 1.5 wt% SSF. Preferably, a tablet disclosed herein comprises at least about 1 wt% SSF.

[0210] In some embodiments, the tablet comprises at most about 2.5 wt%, or at most about 2 wt%, or at most about 1.5 wt% SSF. Preferably, a tablet disclosed herein comprises at most about 2 wt% SSF.

[0211] In some embodiments, tablets disclosed herein comprise at least about 0.1 wt% and at most about 2.5 wt% SSF, or at least about 0.5 wt% and at most about 2 wt% SSF, or at least about 1 wt% and at most about 2 wt% SSF, or at least about 1 wt% and at most about 1.5 wt% SSF, or at least about 1.5 wt% and at most about 2 wt% SSF.

[0212] Preferably, tablets disclosed herein comprise at least about 0.5 wt% SSF and at most about 2 wt% SSF. More preferably, a tablet disclosed herein comprises at least about 1 wt% and at most about 2 wt% SSF. Most preferably, tablets disclosed herein comprise about 1.5 wt% SSF.

[0213] In some embodiments, an amount of SSF may be provided intragranularly. In some embodiments, an amount of SSF may be provided extragranularly. In some embodiments, an amount of SSF may be provided intragranularly and an amount of SSF may be provided extragranularly.

[0214] In some embodiments, about 0.5 wt% SSF is provided extragranularly. In some embodiments, about 1 wt% SSF is provided intragranularly. In some embodiments, about 0.5 wt% SSF is provided extragranularly and about 1 wt% SSF is provided intragranularly. In some embodiments, the tablet comprises about 1.5 wt% SSF, and about 0.5 wt% SSF is provided extragranularly and about 1 wt% or about 1.0 wt% SSF is provided intragranularly.Intragranular and extragranular- MCC, SSF, PVPcI

[0215] In some embodiments, wherein a tablet comprises MCC, SSF and / or PVPcI, amounts of the MCC, SSF and / or PVPcI are provided extragranularly. In some embodiments, wherein a tablet comprises MCC, SSF and / or PVPcI, amounts of the MCC, SSF and PVPcI are provided intragranularly. In some embodiments, wherein a tabletcomprises MCC, SSF and / or PVPcI, amounts of the MCC, SSF and / or PVPcI are provided extragranularly and amounts of the MCC, SSF and / or PVPcI are provided intragranularly.

[0216] The use of an amount of SSF as an extragranular component aids in lubrication during the manufacturing process. The use of an amount of MCC and / or PVPcI as extragranular components may aid the dissolution and / or disintegration of the tablet. The use of MCC and PVPcI as extragranular components may result in an improvement of dissolution and / or disintegration of the tablet that is greater than the use of either component alone as an extragranular component.

[0217] In some embodiments, the tablet comprises about 45 wt% MCC to about 65 wt% MCC, wherein about 5 wt% to about 10 wt% MCC is provided extragranularly and about 40 wt% to about 55 wt% MCC is provided intragranularly, and about 4.5 wt% PVPcI to about 11 wt% PVPcI, wherein about 1 wt% to about 4 wt% PVPcI is provided extragranularly and wherein about 3.5 wt% to about 7 wt% PVPcI is provided intragranularly.

[0218] In some embodiments, the tablet comprises about 45 wt% MCC to about 65 wt% MCC, wherein about 5 wt% to about 10 wt% MCC is provided extragranularly and about 40 wt% to about 55 wt% MCC is provided intragranularly, and about 10 wt% PVPcI, wherein about 3 wt% PVPcI is provided extragranularly and wherein about 7 wt% PVPcI is provided intragranularly.

[0219] In some embodiments, the tablet comprises about 45 wt% MCC to about 65 wt% MCC, wherein about 5 wt% to about 10 wt% MCC is provided extragranularly and wherein about 40 wt% to about 55 wt% MCC is provided intragranularly, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and wherein about 1 wt% is provided intragranularly.

[0220] In some embodiments, the tablet comprises about 53 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and wherein about 46 wt% MCC is provided intragranularly, and about 10 wt% PVPcI, wherein about 3 wt% PVPcI is provided extragranularly and wherein about 7 wt% PVPcI is provided intragranularly

[0221] In some embodiments, the tablet comprises about 53 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and wherein about 46 wt% MCC is provided intragranularly, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and wherein about 1 wt% SSF is provided intragranularly.

[0222] In some embodiments, the tablet comprises about 60 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and wherein about 53 wt% MCC is providedintragranularly, and about 10 wt% PVPcI, wherein about 3 wt% PVPcI is provided extragranularly and wherein about 7 wt% PVPcI is provided intragranularly.

[0223] In some embodiments, the tablet comprises about 60 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and wherein about 53 wt% MCC is provided intragranularly, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and wherein about 1 wt% SSF is provided intragranularly.

[0224] In some embodiments, wherein a tablet comprises MCC, SSF and PVPcI, amounts of MCC, SSF and PVPcI are provided extragranularly. In some embodiments, wherein a tablet comprises MCC, SSF and PVPcI, amounts of MCC, SSF and PVPcI are provided intragranularly. In some embodiments, wherein a tablet comprises MCC, SSF and PVPcI, amounts of MCC, SSF and PVPcI are provided extragranularly and amounts of MCC, SSF and PVPcI are provided intragranularly.

[0225] In some embodiments, the tablet comprises about 45 wt% MCC to about 65 wt% MCC, wherein about 5 wt% to about 10 wt% MCC is provided extragranularly and about 40 wt% to about 55 wt% MCC is provided intragranularly, and about 10 wt% PVPcI, wherein about 3 wt% PVPcI is provided extragranularly and wherein about 7 wt% PVPcI is provided intragranularly, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and wherein about 1 wt% is provided intragranularly.

[0226] In some embodiments, the tablet comprises about 53 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and about 46 wt% MCC is provided intragranularly, and about 10 wt% PVPcI, wherein about 3 wt% PVPcI is provided extragranularly and wherein about 7 wt% PVPcI is provided intragranularly, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and wherein about 1 wt% is provided intragranularly.

[0227] In some embodiments, the tablet comprises about 60 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and about 53 wt% MCC is provided intragranularly, and about 10 wt% PVPcI, wherein about 3 wt% PVPcI is provided extragranularly and wherein about 7 wt% PVPcI is provided intragranularly, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and wherein about 1 wt% is provided intragranularly.Tablet formulations

[0228] In the invention, a tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 10 wt% of alvelestat free base.

[0229] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base. In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base.

[0230] In some embodiments, the tablet further comprises MCC and PVPcI.

[0231] In some embodiments, the tablet further comprises MCC and SLS.

[0232] In some embodiments, the tablet further comprises MCC and DCP.

[0233] In some embodiments, the tablet further comprises MCC and SSF.

[0234] In some embodiments, the tablet further comprises PVPcI and SLS.

[0235] In some embodiments, the tablet further comprises PVPcI and DCP.

[0236] In some embodiments, the tablet further comprises PVPcI and SSF.

[0237] In some embodiments, the tablet further comprises SLS and DCP.

[0238] In some embodiments, the tablet further comprises SLS and SSF.

[0239] In some embodiments, the tablet further comprises DCP and SSF.

[0240] In some embodiments, the tablet further comprises MCC, PVPcI, and SLS.

[0241] In some embodiments, the tablet further comprises MCC, PVPcI, and DCP.

[0242] In some embodiments, the tablet further comprises MCC, PVPcI, and SSF.

[0243] In some embodiments, the tablet further comprises MCC, SLS, and DCP.

[0244] In some embodiments, the tablet further comprises MCC, SLS, and SSF.

[0245] In some embodiments, the tablet further comprises MCC, DCP, and SSF.

[0246] In some embodiments, the tablet further comprises PVPcI, SLS, and DCP.

[0247] In some embodiments, the tablet further comprises PVPcI, SLS, and SSF.

[0248] In some embodiments, the tablet further comprises PVPcI, DCP, and SSF

[0249] In some embodiments, the tablet further comprises SLS, DCP, and SSF.

[0250] In some embodiments, the tablet further comprises MCC, PVPcI, SLS, and DCP.

[0251] In some embodiments, the tablet further comprises MCC, PVPcI, SLS, and SSF.

[0252] In some embodiments, the tablet further comprises MCC, PVPcI, DCP, and SSF.

[0253] In some embodiments, the tablet further comprises MCC, SLS, DCP, and SSF.

[0254] In some embodiments, the tablet further comprises PVPcI, SLS, DCP, and SSF.

[0255] In some embodiments, the tablet further comprises MCC, PVPcI, SLS, DCP, and SSF.

[0256] In some embodiments, the tablet comprises at least about 40 wt% and at most about 70 wt% MCC and at least about 3 wt% and at most about 15 wt% PVPcI.

[0257] In some embodiments, the tablet comprises at least about 50 wt% and at most about 62 wt% MCC, and at least about 4.5 wt% and at most about 11 wt% PVPcI.

[0258] In some embodiments, the tablet comprises at least about 40 wt% and at most about 70 wt% MCC, and at least about 0.5 wt% and at most about 2.5 wt% SLS.

[0259] In some embodiments, the tablet comprises at least about 50 wt% and at most about 62 wt% MCC, and at least about 1.1 wt% and at most about 2.2 wt% SLS.

[0260] In some embodiments, the tablet comprises at least about 0.5 wt% and at most about 2.5 wt% SLS, and at least about 3 wt% and at most about 15 wt% PVPcI.

[0261] In some embodiments, the tablet comprises at least about 1.1 wt% and at most about 2.2 wt% SLS, and at least about 4.5 wt% and at most about 11 wt% PVPcI.

[0262] In some embodiments, the tablet comprises at least about 40 wt% and at most about 70 wt% MCC, at least about 3 wt% and at most about 15 wt% PVPcI, and at least about 0.5 wt% and at most about 2.5 wt% SLS.

[0263] In some embodiments, the tablet comprises at least about 50 wt% and at most about 62 wt% MCC, at least about 4.5 wt% and at most about 11 wt% PVPcI, and at least about 1.1 wt% and at most about 2.2 wt% SLS.

[0264] In some embodiments, the tablet comprises at least about 40 wt% and at most about 70 wt% MCC, at least about 3 wt% and at most about 15 wt% PVPcI, at least about 0.5 wt% and at most about 2.5 wt% SLS, and at least about 5 wt% DCP and at most about 10 wt% DCP.

[0265] In some embodiments, the tablet comprises at least about 50 wt% and at most about 62 wt% MCC, at least about 4.5 wt% and at most about 11 wt% PVPcI, at leastabout 1.1 wt% and at most about 2.2 wt% SLS, and at least about 5 wt% DCP and at most about 10 wt% DCP.

[0266] In some embodiments, the tablet comprises at least about 40 wt% and at most about 70 wt% MCC, at least about 3 wt% and at most about 15 wt% PVPcI, at least about 0.5 wt% and at most about 2.5 wt% SLS, at least about 5 wt% DCP and at most about 10 wt% DCP, and at least about 0.5 wt% SSF and at most about 2 wt% SSF.

[0267] In some embodiments, the tablet comprises at least about 50 wt% and at most about 62 wt% MCC, at least about 4.5 wt% and at most about 11 wt% PVPcI, at least about 1.1 wt% and at most about 2.2 wt% SLS, and at least about 5 wt% DCP and at most about 10 wt% DCP, and at least about 0.5 wt% SSF and at most about 2 wt% SSF.

[0268] In some embodiments, the tablet consists of at least about 13.7 wt% and at most about 38.9 wt% alvelestat tosylate, at least about 50 wt% and at most about 62 wt% MCC, at least about 4.5 wt% and at most about 11 wt% PVPcI, at least about 1.1 wt% and at most about 2.2 wt% SLS, and at least about 5 wt% DCP and at most about 10 wt% DCP, and at least about 0.5 wt% SSF and at most about 2 wt% SSF, and optionally, a coating such as a film coating.Tablets providing an amount of alvelestat corresponding to about 20 wt% of alvelestat free base

[0269] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, and the tablet further comprises MCC and PVPcI, or further comprises MCC and SLS, or further comprises PVPcI and SLS.

[0270] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 40 wt% and at most about 70 wt% MCC, and at least about 3 wt% and at most about 15 wt% PVPcI.

[0271] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 50 wt% and at most about 62 wt% MCC, and at least about 4.5 wt% and at most about 11 wt% PVPcI.

[0272] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat freebase, at least about 40 wt% and at most about 70 wt% MCC, and at least about 0.5 wt% and at most about 2.5 wt% SLS.

[0273] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 50 wt% and at most about 62 wt% MCC, and at least about 1.1 wt% and at most about 2.2 wt% SLS.

[0274] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 0.5 wt% and at most about 2.5 wt% SLS, and at least about 3 wt% and at most about 15 wt% PVPcI.

[0275] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 1.1 wt% and at most about 2.2 wt% SLS, and at least about 4.5 wt% and at most about 11 wt% PVPcI.

[0276] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, and the tablet further comprises MCC, PVPcI, and SLS.

[0277] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 40 wt% and at most about 70 wt% MCC, at least about 3 wt% and at most about 15 wt% PVPcI, and at least about 0.5 wt% and at most about 2.5 wt% SLS.

[0278] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 50 wt% and at most about 62 wt% MCC, at least about 4.5 wt% and at most about 11 wt% PVPcI, and at least about 1.1 wt% and at most about 2.2 wt% SLS.

[0279] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, and the tablet further comprises MCC, PVPcI, SLS, and DCP.

[0280] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 40 wt% and at most about 70 wt% MCC, at least about 3 wt% and at most about 15 wt% PVPcI, at least about 0.5 wt% and at most about 2.5 wt% SLS, and at least about 5 wt% DCP and at most about 10 wt% DCP.

[0281] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 50 wt% and at most about 62 wt% MCC, at least about 4.5 wt% and at most about 11 wt% PVPcI, at least about 1.1 wt% and at most about 2.2 wt% SLS, and at least about 5 wt% DCP and at most about 10 wt% DCP.

[0282] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, and the tablet further comprises MCC, PVPcI, SLS, DCP, and SSF.

[0283] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 40 wt% and at most about 70 wt% MCC, at least about 3 wt% and at most about 15 wt% PVPcI, at least about 0.5 wt% and at most about 2.5 wt% SLS, at least about 5 wt% DCP and at most about 10 wt% DCP, and at least about 0.5 wt% SSF and at most about 2 wt% SSF.

[0284] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, at least about 50 wt% and at most about 62 wt% MCC, at least about 4.5 wt% and at most about 11 wt% PVPcI, at least about 1.1 wt% and at most about 2.2 wt% SLS, at least about 5 wt% DCP and at most about 10 wt% DCP, and at least about 0.5 wt% SSF and at most about 2 wt% SSF.

[0285] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 52 wt% to about 55 wt% MCC, about 9 wt% to about 11 wt% PVPcI, and about 1.5 wt% to about 2.5 wt% SLS.

[0286] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 53 wt% MCC, about 9 wt% to about 11 wt% PVPcI, and about 1.5 wt% to about 2.5 wt% SLS.

[0287] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 52 wt% to about 55 wt% MCC, about 10 wt% PVPcI, and about 1.5 wt% to about 2.5 wt% SLS.

[0288] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat freebase, about 52 wt% to about 55 wt% MCC, about 9 wt% to about 11 wt% PVPcI, and about 2 wt% SLS.

[0289] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 53 wt% MCC, about 10 wt% PVPcI, and about 1.5 wt% to about 2.5 wt% SLS.

[0290] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 52 wt% to about 55 wt% MCC, about 10 wt% PVPcI, and about 2 wt% SLS.

[0291] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 53 wt% MCC, about 10 wt% PVPcI, and about 2 wt% SLS.

[0292] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 52 wt% to about 55 wt% MCC, about 9 wt% to about 11 wt% PVPcI, about 1.5 wt% to about 2.5 wt% SLS, about 6.0 wt% to about 7.5 wt% DCP, and about 1 wt% to about 2 wt% SSF.

[0293] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 53 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 6.0 wt% to about 7.5 wt% DCP, and about 1 wt% to about 2 wt% SSF.

[0294] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 53 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 6.0 wt% to about 7.5 wt% DCP, and about 1.5 wt% SSF.

[0295] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 53 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 7 wt% DCP, and about 1 wt% to about 2 wt% SSF.

[0296] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 53 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF.

[0297] In some embodiments, the tablet comprises about 26 wt% alvelestat tosylate, about 53 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF.

[0298] In some embodiments, the tablet comprises about 26.3 wt% alvelestat tosylate, about 53.4 wt% MCC, about 10.0 wt% PVPcI, about 2.0 wt% SLS, about 6.8 wt% DCP, and about 1.5 wt% SSF.

[0299] In one embodiment, the tablet consists of about 26 wt% alvelestat tosylate, about 53 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF, and optionally, a coating such as a film coating.

[0300] In one embodiment, the tablet consists of about 26.3 wt% alvelestat tosylate, about 53.4 wt% MCC, about 10.0 wt% PVPcI, about 2.0 wt% SLS, about 6.8 wt% DCP, about 1.5 wt% SSF, and optionally, a coating such as a film coating.

[0301] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base, about 53 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and about 46 wt% MCC is provided intragranularly, about 10 wt% PVPcI, wherein about 3 wt% PVPcI is provided extragranularly and about 7 wt% PVPcI is provided intragranularly, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and about 1 wt% SSF is provided intragranularly.

[0302] In some embodiments, the tablet comprises about 26 wt% alvelestat tosylate, about 53 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and about 46 wt% MCC is provided intragranularly, about 10 wt% PVPcI, wherein about 3 wt% PVPcI is provided extragranularly and about 7 wt% PVPcI is provided intragranularly, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and about 1 wt% SSF is provided intragranularly.

[0303] In some embodiments, the tablet comprises about 26.3 wt% alvelestat tosylate, about 53.4 wt% MCC, wherein about 7.0 wt% MCC is provided extragranularly and about 46.4 wt% MCC is provided intragranularly, about 10.0 wt% PVPcI, wherein about 3.0 wt% PVPcI is provided extragranularly and about 7.0 wt% PVPcI is provided intragranularly, about 2.0 wt% SLS, about 6.8 wt% DCP, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and about 1 wt% SSF is provided intragranularly.

[0304] In one embodiment, the tablet consists of about 26 wt% alvelestat tosylate, about 53 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and about 46 wt% MCC is provided intragranularly, about 10 wt% PVPcI, wherein about 3 wt% PVPcI isprovided extragranularly and about 7 wt% PVPcI is provided intragranularly, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and about 1 wt% SSF is provided intragranularly, and optionally, a coating such as a film coating.

[0305] In one embodiment, the tablet consists of about 26.3 wt% alvelestat tosylate, about 53.4 wt% MCC, wherein about 7.0 wt% MCC is provided extragranularly and about 46.4 wt% MCC is provided intragranularly, about 10.0 wt% PVPcI, wherein about 3.0 wt% PVPcI is provided extragranularly and about 7.0 wt% PVPcI is provided intragranularly, about 2.0 wt% SLS, about 6.8 wt% DCP, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and about 1 wt% SSF is provided intragranularly, and optionally, a coating such as a film coating.

[0306] In some embodiments, the tablet comprises about 26 wt% alvelestat tosylate, about 59 wt% MCC, about 5 wt% PVPcI, about 1 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF.

[0307] In some embodiments, the tablet comprises about 26.3 wt% alvelestat tosylate, about 58.6 wt% MCC, about 5.4 wt% PVPcI, about 1.4 wt% SLS, about 6.8 wt% DCP, and about 1.5 wt% SSF.

[0308] In one embodiment, the tablet consists of about 26 wt% alvelestat tosylate, about 59 wt% MCC, about 5 wt% PVPcI, about 1 wt% SLS, about 7 wt% DCP, about 1.5 wt% SSF, and optionally, a coating such as a film coating.

[0309] In one embodiment, the tablet consists of about 26.3 wt% alvelestat tosylate, about 58.6 wt% MCC, about 5.4 wt% PVPcI, about 1.4 wt% SLS, about 6.8 wt% DCP, about 1.5 wt% SSF, and optionally, a coating such as a film coating.120 mg tablet

[0310] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 312 mg to about 330 mg MCC, about 54 mg to about 66 mg PVPcI, and about 9 mg to about 15 mg SLS.

[0311] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 320 mg MCC, about 54 mg to about 66 mg PVPcI, and about 9 mg to about 15 mg SLS.

[0312] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 312 mg to about 330 mg MCC, about 60 mg PVPcI, and about 9 mg to about 15 mg SLS.

[0313] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 312 mg to about 330 mg MCC, about 54 mg to about 66 mg PVPcI, and about 12 mg SLS.

[0314] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 320 mg MCC, about 60 mg PVPcI, and about 9 mg to about 15 mg SLS.

[0315] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 312 mg to about 330 mg MCC, about 60 mg PVPcI, and about 12 mg SLS.

[0316] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 320 mg MCC, about 60 mg PVPcI, and about 12 mg SLS.

[0317] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 312 mg to about 330 mg MCC, about 54 mg to about 66 mg PVPcI, about 9 mg to about 15 mg SLS, about 36 mg to about 45 mg DCP, and about 6 mg to about 12 mg SSF.

[0318] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 320 mg MCC, about 60 mg PVPcI, about 12 mg SLS, about 36 mg to about 45 mg DCP, and about 6 mg to about 12 mg SSF.

[0319] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 320 mg MCC, about 60 mg PVPcI, about 12 mg SLS, about 36 mg to about 45 mg DCP, and about 9 mg SSF.

[0320] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 320 mg MCC, about 60 mg PVPcI, about 12 mg SLS, about 41 mg DCP, and about 6 mg to about 12 mg SSF.

[0321] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 320 mg MCC, about 60 mg PVPcI, about 12 mg SLS, about 41 mg DCP, and about 9 mg SSF.

[0322] In some embodiments, the tablet providing an amount of 120 mg of alvelestat free base comprises about 158 mg alvelestat tosylate, about 320 mg MCC, about 60 mg PVPcI, about 12 mg SLS, about 41 mg DCP, about 9 mg SSF.

[0323] In some embodiments, the tablet providing an amount of 120 mg of alvelestat free base comprises about 157.9 mg alvelestat tosylate, about 320.3 mg MCC, about 60.0 mg PVPcI, about 12.0 mg SLS, about 40.8 mg DCP, about 9.0 mg SSF.

[0324] In one embodiment, the tablet providing an amount of 120 mg of alvelestat free base consists of about 158 mg alvelestat tosylate, about 320 mg MCC, about 60 mg PVPcI, about 12 mg SLS, about 41 mg DCP, about 9 mg SSF, such that the total core weight of the tablet is about 600 mg, and optionally, a coating such as a film coating.

[0325] In one embodiment, the tablet providing an amount of 120 mg of alvelestat free base consists of about 157.9 mg alvelestat tosylate, about 320.3 mg MCC, about 60.0 mg PVPcI, about 12.0 mg SLS, about 40.8 mg DCP, about 9.0 mg SSF, such that the total core weight of the tablet is about 600 mg, and optionally, a coating such as a film coating.

[0326] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 320 mg MCC, wherein about 42 mg MCC is provided extragranularly and about 278 mg MCC is provided intragranularly, about 60 mg PVPcI, wherein about 18 mg PVPcI is provided extragranularly and about 42 mg PVPcI is provided intragranularly, about 12 mg SLS, about 41 mg DCP, and about 9 mg SSF, wherein about 3 mg SSF is provided extragranularly and about 6 mg SSF is provided intragranularly.

[0327] In some embodiments, the tablet providing an amount of 120 mg of alvelestat free base comprises about 158 mg alvelestat tosylate, about 320 mg MCC, wherein about 42 mg MCC is provided extragranularly and about 278 mg MCC is provided intragranularly, about 60 mg PVPcI, wherein about 18 mg PVPcI is provided extragranularly and about 42 mg PVPcI is provided intragranularly, about 12 mg SLS, about 41 mg DCP, and about 9 mg SSF, wherein about 3 mg SSF is provided extragranularly and about 6 mg SSF is provided intragranularly.

[0328] In some embodiments, the tablet providing an amount of 120 mg of alvelestat free base comprises about 157.9 mg alvelestat tosylate, about 320.3 mg MCC, wherein about 42.0 mg MCC is provided extragranularly and about 278.3 mg MCC is providedintragranularly, about 60.0 mg PVPcI, wherein about 18.0 mg PVPcI is provided extragranularly and about 42.0 mg PVPcI is provided intragranularly, about 12.0 mg SLS, about 40.8 mg DCP, about 9.0 mg SSF, wherein about 3.0 mg SSF is provided extragranularly and about 6.0 mg SSF is provided intragranularly.

[0329] In one embodiment, the tablet providing an amount of 120 mg of alvelestat free base consists of about 158 mg alvelestat tosylate, about 320 mg MCC, wherein about 42 mg MCC is provided extragranularly and about 278 mg MCC is provided intragranularly, about 60 mg PVPcI, wherein about 18 mg PVPcI is provided extragranularly and about 42 mg PVPcI is provided intragranularly, about 12 mg SLS, about 41 mg DCP, and about 9 mg SSF, wherein about 3 mg SSF is provided extragranularly and about 6 mg SSF is provided intragranularly, such that the total core weight of the tablet is about 600 mg, and optionally, a coating such as a film coating.

[0330] In one embodiment, the tablet providing an amount of 120 mg of alvelestat free base consists of about 157.9 mg alvelestat tosylate, about 320.3 mg MCC, wherein about 42.0 mg MCC is provided extragranularly and about 278.3 mg MCC is provided intragranularly, about 60.0 mg PVPcI, wherein about 18.0 mg PVPcI is provided extragranularly and about 42.0 mg PVPcI is provided intragranularly, about 12.0 mg SLS, about 40.8 mg DCP, about 9.0 mg SSF, wherein about 3.0 mg SSF is provided extragranularly and about 6.0 mg SSF is provided intragranularly, such that the total core weight of the tablet is about 600 mg, and optionally, a coating such as a film coating.60 mg tablet

[0331] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 156 mg to about 165 mg MCC, about 27 mg to about 33 mg PVPcI, and about 4.5 mg to about 7.5 mg SLS.

[0332] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 160 mg MCC, about 30 mg PVPcI, and about 6 mg SLS.

[0333] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 156 mg to about 165 mg MCC, about 27 mg to about 33 mg PVPcI, and about 4.5 mg to about 7.5 mg SLS, about 18 mg to about 23 mg DCP, and about 3 mg to about 6 mg SSF.

[0334] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 160 mg MCC, about 30 mg PVPcI, and about 6 mg SLS, about 20 mg DCP, and about 5 mg SSF.

[0335] In some embodiments, the tablet providing an amount of 60 mg of alvelestat free base comprises about 79 mg alvelestat tosylate, about 160 mg MCC, about 30 mg PVPcI, about 6 mg SLS, about 20 mg DCP, and about 5 mg SSF.

[0336] In some embodiments, the tablet providing an amount of 60 mg of alvelestat free base comprises about 79.0 mg alvelestat tosylate, about 160.2 mg MCC, about 30.0 mg PVPcI, about 6.0 mg SLS, about 20.4 mg DCP, about 4.5 mg SSF.

[0337] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79 mg alvelestat tosylate, about 160 mg MCC, about 30 mg PVPcI, about 6 mg SLS, about 20 mg DCP, and about 5 mg SSF, such that the total core weight of the tablet is about 300 mg, and optionally, a coating such as a film coating.

[0338] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79.0 mg alvelestat tosylate, about 160.2 mg MCC, about 30.0 mg PVPcI, about 6.0 mg SLS, about 20.4 mg DCP, and about 4.5 mg SSF, such that the total core weight of the tablet is about 300 mg, and optionally, a coating such as a film coating.

[0339] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 160 mg MCC, wherein about 21 mg MCC is provided extragranularly and about 139 mg MCC is provided intragranularly, about 30 mg PVPcI, wherein about 9 mg PVPcI is provided extragranularly and about 21 mg PVPcI is provided intragranularly, and about 6 mg SLS, about 20 mg DCP, and about 5 mg SSF, wherein about 1.5 mg SSF is provided extragranularly and about 3 mg SSF is provided intragranularly.

[0340] In some embodiments, the tablet providing an amount of 60 mg of alvelestat free base comprises about 79 mg alvelestat tosylate, about 160 mg MCC, wherein about 21 mg MCC is provided extragranularly and about 139 mg MCC is provided intragranularly, about 30 mg PVPcI, wherein about 9 mg PVPcI is provided extragranularly and about 21 mg PVPcI is provided intragranularly, and about 6 mg SLS, about 20 mg DCP, and about 5 mg SSF, wherein about 1.5 mg SSF is provided extragranularly and about 3 mg SSF is provided intragranularly.

[0341] In some embodiments, the tablet providing an amount of 60 mg of alvelestat free base comprises about 79.0 mg alvelestat tosylate, about 160.2 mg MCC, wherein about 21.0 mg MCC is provided extragranularly and about 139.2 mg MCC is providedintragranularly, about 30.0 mg PVPcI, wherein about 9.0 mg PVPcI is provided extragranularly and about 21.0 mg PVPcI is provided intragranularly, about 6.0 mg SLS, about 20.4 mg DCP, about 4.5 mg SSF, wherein about 1.5 mg SSF is provided extragranularly and about 3.0 mg SSF is provided intragranularly.

[0342] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79 mg alvelestat tosylate, about 160 mg MCC, wherein about 21 mg MCC is provided extragranularly and about 139 mg MCC is provided intragranularly, about 30 mg PVPcI, wherein about 9 mg PVPcI is provided extragranularly and about 21 mg PVPcI is provided intragranularly, and about 6 mg SLS, about 20 mg DCP, and about 5 mg SSF, wherein about 1.5 mg SSF is provided extragranularly and about 3.0 mg SSF is provided intragranularly, such that the total core weight of the tablet is about 300 mg, and optionally, a coating such as a film coating.

[0343] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79.0 mg alvelestat tosylate, about 160.2 mg MCC, wherein about 21 mg MCC is provided extragranularly and about 139.2 mg MCC is provided intragranularly, about 30.0 mg PVPcI, wherein about 9.0 mg PVPcI is provided extragranularly and about 21.0 mg PVPcI is provided intragranularly, about 6.0 mg SLS, about 20.4 mg DCP, about 4.5 mg SSF, wherein about 1.5 mg SSF is provided extragranularly and about 3.0 mg SSF is provided intragranularly, such that the total core weight of the tablet is about 300 mg, and optionally, a coating such as a film coating.Tablets providing an amount of alvelestat corresponding to about 15 wt% of alvelestat free base

[0344] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, and the tablet further comprises MCC and PVPcI, or further comprises MCC and SLS, or further comprises PVPcI and SLS.

[0345] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 40 wt% and at most about 70 wt% MCC, and at least about 3 wt% and at most about 15 wt% PVPcI.

[0346] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 50 wt% and at most about 62 wt% MCC, and at least about 4.5 wt% and at most about 11 wt% PVPcI.

[0347] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 40 wt% and at most about 70 wt% MCC, and at least about 0.5 wt% and at most about 2.5 wt% SLS.

[0348] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 50 wt% and at most about 62 wt% MCC, and at least about 1.1 wt% and at most about 2.2 wt% SLS.

[0349] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 0.5 wt% and at most about 2.5 wt% SLS, and at least about 3 wt% and at most about 15 wt% PVPcI.

[0350] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 1.1 wt% and at most about 2.2 wt% SLS, and at least about 4.5 wt% and at most about 11 wt% PVPcI.

[0351] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, and the tablet further comprises MCC, PVPcI, and SLS.

[0352] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 40 wt% and at most about 70 wt% MCC, at least about 3 wt% and at most about 15 wt% PVPcI, and at least about 0.5 wt% and at most about 2.5 wt% SLS.

[0353] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 50 wt% and at most about 62 wt% MCC, at least about 4.5 wt% and at most about 11 wt% PVPcI, and at least about 1.1 wt% and at most about 2.2 wt% SLS.

[0354] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, and the tablet further comprises MCC, PVPcI, SLS, and DCP.

[0355] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 40 wt% and at most about 70 wt% MCC, at least about 3 wt% and atmost about 15 wt% PVPcI, at least about 0.5 wt% and at most about 2.5 wt% SLS, and at least about 5 wt% DCP and at most about 10 wt% DCP.

[0356] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 50 wt% and at most about 62 wt% MCC, at least about 4.5 wt% and at most about 11 wt% PVPcI, at least about 1.1 wt% and at most about 2.2 wt% SLS, and at least about 5 wt% DCP and at most about 10 wt% DCP.

[0357] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, and the tablet further comprises MCC, PVPcI, SLS, DCP, and SSF.

[0358] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 40 wt% and at most about 70 wt% MCC, at least about 3 wt% and at most about 15 wt% PVPcI, at least about 0.5 wt% and at most about 2.5 wt% SLS, at least about 5 wt% DCP and at most about 10 wt% DCP, and at least about 0.5 wt% SSF and at most about 2 wt% SSF.

[0359] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, at least about 50 wt% and at most about 62 wt% MCC, at least about 4.5 wt% and at most about 11 wt% PVPcI, at least about 1.1 wt% and at most about 2.2 wt% SLS, at least about 5 wt% DCP and at most about 10 wt% DCP, and at least about 0.5 wt% SSF and at most about 2 wt% SSF.

[0360] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 58 wt% to about 62 wt% MCC, about 9 wt% to about 11 wt% PVPcI, and about 1.5 wt% to about 2.5 wt% SLS.

[0361] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 60 wt% MCC, about 9 wt% to about 11 wt% PVPcI, and about 1.5 wt% to about 2.5 wt% SLS.

[0362] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 58 wt% to about 62 wt% MCC, about 10 wt% PVPcI, and about 1.5 wt% to about 2.5 wt% SLS.

[0363] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 58 wt% to about 62 wt% MCC, about 9 wt% to about 11 wt% PVPcI, and about 2 wt% SLS.

[0364] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 60 wt% MCC, about 10 wt% PVPcI, and about 1.5 wt% to about 2.5 wt% SLS.

[0365] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 58 wt% to about 62 wt% MCC, about 10 wt% PVPcI, and about 2 wt% SLS.

[0366] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 60 wt% MCC, about 10 wt% PVPcI, and about 2 wt% SLS.

[0367] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 58 wt% to about 62 wt% MCC, about 9 wt% to about 11 wt% PVPcI, about 1.5 wt% to about 2.5 wt% SLS, about 6.0 wt% to about 7.5 wt% DCP, and about 1 wt% to about 2 wt% SSF.

[0368] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 60 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 6.0 wt% to about 7.5 wt% DCP, and about 1 wt% to about 2 wt% SSF.

[0369] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 60 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 6.0 wt% to about 7.5 wt% DCP, and about 1.5 wt% SSF.

[0370] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 60 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 7 wt% DCP, and about 1 wt% to about 2 wt% SSF.

[0371] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 60 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF.

[0372] In some embodiments, the tablet comprises about 20 wt% alvelestat tosylate, about 60 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF.

[0373] In some embodiments, the tablet comprises about 19.8 wt% alvelestat tosylate, about 60.0 wt% MCC, about 10.0 wt% PVPcI, about 2.0 wt% SLS, about 6.8 wt% DCP, and about 1.5 wt% SSF.

[0374] In one embodiment, the tablet consists of about 20 wt% alvelestat tosylate, about 60 wt% MCC, about 10 wt% PVPcI, about 2 wt% SLS, about 7 wt% DCP, about 1.5 wt% SSF, and optionally, a coating such as a film coating.

[0375] In one embodiment, the tablet consists of about 19.8 wt% alvelestat tosylate, about 60.0 wt% MCC, about 10.0 wt% PVPcI, about 2.0 wt% SLS, about 6.8 wt% DCP, about 1.5 wt% SSF, and optionally, a coating such as a film coating.

[0376] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base, about 60 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and about 53 wt% MCC is provided intragranularly, about 10 wt% PVPcI, wherein about 3 wt% PVPcI is provided extragranularly and about 7 wt% PVPcI is provided intragranularly, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and about 1 wt% SSF is provided intragranularly.

[0377] In some embodiments, the tablet comprises about 20 wt% alvelestat tosylate, about 60 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and about 53 wt% MCC is provided intragranularly, about 10 wt% PVPcI, wherein about 3 wt% PVPcI is provided extragranularly and about 7 wt% PVPcI is provided intragranularly, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and about 1 wt% SSF is provided intragranularly.

[0378] In some embodiments, the tablet comprises about 19.8 wt% alvelestat tosylate, about 60.0 wt% MCC, wherein about 7.0 wt% MCC is provided extragranularly and about 53.2 wt% MCC is provided intragranularly, about 10.0 wt% PVPcI, wherein about 3.0 wt% PVPcI is provided extragranularly and about 7.0 wt% PVPcI is provided intragranularly, about 2.0 wt% SLS, about 6.8 wt% DCP, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and about 1.0 wt% SSF is provided intragranularly.

[0379] In one embodiment, the tablet consists of about 20 wt% alvelestat tosylate, about 60 wt% MCC, wherein about 7 wt% MCC is provided extragranularly and about 53 wt% MCC is provided intragranularly, about 10 wt% PVPcI, wherein about 3 wt% PVPcI isprovided extragranularly and about 7 wt% PVPcI is provided intragranularly, about 2 wt% SLS, about 7 wt% DCP, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and about 1 wt% SSF is provided intragranularly, and optionally, a coating such as a film coating.

[0380] In one embodiment, the tablet consists of about 19.8 wt% alvelestat tosylate, about 60.0 wt% MCC, wherein about 7.0 wt% MCC is provided extragranularly and about 53.2 wt% MCC is provided intragranularly, about 10.0 wt% PVPcI, wherein about 3.0 wt% PVPcI is provided extragranularly and about 7.0 wt% PVPcI is provided intragranularly, about 2.0 wt% SLS, about 6.8 wt% DCP, and about 1.5 wt% SSF, wherein about 0.5 wt% SSF is provided extragranularly and about 1.0 wt% SSF is provided intragranularly, and optionally, a coating such as a film coating.60 mg tablet

[0381] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 232 mg to about 248 mg MCC, about 36 mg to about 44 mg PVPcI, and about 6 mg to about 10 mg SLS.

[0382] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 240 mg MCC, about 36 mg to about 44 mg PVPcI, and about 6 mg to about 10 mg SLS.

[0383] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 232 mg to about 248 mg MCC, about 40 mg PVPcI, and about 6 mg to about 10 mg SLS.

[0384] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 232 mg to about 248 mg MCC, about 36 mg to about 44 mg PVPcI, and about 8 mg SLS.

[0385] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 240 mg MCC, about 40 mg PVPcI, and about 6 mg to about 10 mg SLS.

[0386] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 232 mg to about 248 mg MCC, about 40 mg PVPcI, and about 8 mg SLS.

[0387] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 240 mg MCC, about 40 mg PVPcI, and about 8 mg SLS.

[0388] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 232 mg to about 248 mg MCC, about 36 mg to about 44 mg PVPcI, about 6 mg to about 10 mg SLS, about 24 mg to about 30 mg DCP, and about 4 mg to about 8 mg SSF.

[0389] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 240 mg MCC, about 40 mg PVPcI, about 8 mg SLS, about 24 mg to about 30 mg DCP, and about 4 mg to about 8 mg SSF.

[0390] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 240 mg MCC, about 40 mg PVPcI, about 8 mg SLS, about 24 mg to about 30 mg DCP, and about 6 mg SSF.

[0391] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 240 mg MCC, about 40 mg PVPcI, about 8 mg SLS, about 27 mg DCP, and about 4 mg to about 8 mg SSF.

[0392] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 240 mg MCC, about 40 mg PVPcI, about 8 mg SLS, about 27 mg DCP, and about 6 mg SSF.

[0393] In some embodiments, the tablet providing an amount of 60 mg of alvelestat free base comprises about 79 mg alvelestat tosylate, about 240 mg MCC, about 40 mg PVPcI, about 8 mg SLS, about 27 mg DCP, and about 6 mg SSF.

[0394] In some embodiments, the tablet providing an amount of 60 mg of alvelestat free base comprises about 79.0 mg alvelestat tosylate, about 239.8 mg MCC, about 40.0 mg PVPcI, about 8.0 mg SLS, about 27.2 mg DCP, and about 6.0 mg SSF.

[0395] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79 mg alvelestat tosylate, about 240 mg MCC, about 40 mg PVPcI, about 8 mg SLS, about 27 mg DCP, and about 6 mg SSF, such that the total core weight of the tablet is about 400 mg, and optionally, a coating such as a film coating.

[0396] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79.0 mg alvelestat tosylate, about 239.8 mg MCC, about 40.0 mg PVPcI, about 8.0 mg SLS, about 27.2 mg DCP, and about 6.0 mg SSF, such that the total core weight of the tablet is about 400 mg, and optionally, a coating such as a film coating.

[0397] In some embodiments, the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 240 mg MCC, wherein about 28 mg MCC is provided extragranularly and about 212 mg MCC is provided intragranularly, about 40 mg PVPcI, wherein about 12 mg PVPcI is provided extragranularly and about 8 mg PVPcI is provided intragranularly, about 8 mg SLS, about 27 mg DCP, and about 6 mg SSF, wherein about 2 mg SSF is provided extragranularly and about 4 mg SSF is provided intragranularly.

[0398] In some embodiments, the tablet providing an amount of 60 mg of alvelestat free base comprises about 79 mg alvelestat tosylate, about 240 mg MCC, wherein about 28 mg MCC is provided extragranularly and about 212 mg MCC is provided intragranularly, about 40 mg PVPcI, wherein about 12 mg PVPcI is provided extragranularly and about 8 mg PVPcI is provided intragranularly, about 8 mg SLS, about 27 mg DCP, and about 6 mg SSF, wherein about 2 mg SSF is provided extragranularly and about 4 mg SSF is provided intragranularly.

[0399] In some embodiments, the tablet providing an amount of 60 mg of alvelestat free base comprises about 79.0 mg alvelestat tosylate, about 239.8 mg MCC, wherein about 28.0 mg MCC is provided extragranularly and about 211.8 mg MCC is provided intragranularly, about 40.0 mg PVPcI, wherein about 12.0 mg PVPcI is provided extragranularly and about 8.0 mg PVPcI is provided intragranularly, about 8.0 mg SLS, about 27.2 mg DCP, and about 6.0 mg SSF, wherein about 2.0 mg SSF is provided extragranularly and about 4.0 mg SSF is provided intragranularly.

[0400] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79 mg alvelestat tosylate, about 240 mg MCC, wherein about 28 mg MCC is provided extragranularly and about 212 mg MCC is provided intragranularly, about 40 mg PVPcI, wherein about 12 mg PVPcI is provided extragranularly and about 8 mg PVPcI is provided intragranularly, about 8 mg SLS, about 27 mg DCP, and about 6 mg SSF, wherein about 2 mg SSF is provided extragranularly and about 4 mg SSF is provided intragranularly, such that the total core weight of the tablet is about 400 mg, and optionally, a coating such as a film coating.

[0401] In one embodiment, the tablet providing an amount of 60 mg of alvelestat free base consists of about 79.0 mg alvelestat tosylate, about 239.8 mg MCC, wherein about28.0 mg MCC is provided extragranularly and about 211.8 mg MCC is provided intragranularly, about 40.0 mg PVPcI, wherein about 12.0 mg PVPcI is provided extragranularly and about 8.0 mg PVPcI is provided intragranularly, about 8.0 mg SLS, about 27.2 mg DCP, and about 6.0 mg SSF, wherein about 2.0 mg SSF is provided extragranularly and about 4.0 mg SSF is provided intragranularly, such that the total core weight of the tablet is about 400 mg, and optionally, a coating such as a film coating.Dissolution profile

[0402] Tablets of the invention may have favourable dissolution properties, making them particularly useful in therapeutic applications. The tablets disclosed herein are preferably immediate release tablets.

[0403] A dissolution profile of a tablet as disclosed herein can be measured using apparatus and methodology described in US / European and Japanese Pharmacopoeia, for example USP <711> Dissolution which uses a USP II paddle apparatus. The dissolution profile may be carried out in any pH conditions, e.g. wherein the solution is buffered to pH 6.8 or to pH 1.1. The dissolution medium for pH 6.8 may be a 50 mM phosphate buffer, and the dissolution medium for pH 1.1 may be HCI. The dissolution medium may be provided in a volume according to the tablet, e.g. a 900 mL volume of dissolution medium may be used for a tablet providing 60 mg or 120 mg of alvelestat free base. The dissolution medium temperature may be 37°C ± 0.5°C. The rotation speed may be 75 rpm or 100 rpm.

[0404] In some embodiments, the tablet of the invention releases at least about 70 %, at least about 75 %, at least about 80 %, at least about 85 %, or at least about 90 % of alvelestat or a pharmaceutically salt thereof in about 60 minutes at pH 6.8. Preferably, a tablet of the invention releases at least about 90 % of alvelestat or a pharmaceutically acceptable salt thereof in about 60 minutes at pH 6.8.

[0405] In some embodiments, the tablet of the invention releases at least about 70 %, at least about 75 %, at least about 80 %, at least about 85 %, or at least about 90 % alvelestat or a pharmaceutically acceptable salt thereof in about 60 minutes at pH 1.1.

[0406] In some embodiments, the tablet of the invention releases at least about 70 %, at least about 75 %, at least about 80 %, at least about 85 %, or at least about 90 % of alvelestat or a pharmaceutically salt thereof in about 60 minutes at pH 6.8, and at least about 75 %, at least about 80 %, at least about 85 %, or at least about 90 % of alvelestat or a pharmaceutically salt thereof in about 60 minutes at pH 1.1. Preferably, a tablet of theinvention releases at least about 90 % of alvelestat or a pharmaceutically acceptable salt thereof in about 60 minutes at pH 6.8 and at least about 90 % of alvelestat or a pharmaceutically acceptable salt thereof in about 60 minutes at pH 1.1.Manufacturing methods

[0407] Methods for producing the pharmaceutical formulations disclosed herein are also provided. These methods may be performed on blends having the compositions disclosed herein. In general, tableting methods are well known in the art of pharmacy. Techniques and formulations generally are found in Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, PA), which is hereby incorporated by reference herein in its entirety.

[0408] A tablet can be made by compression or molding, optionally with one or more excipients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with excipients.

[0409] In some embodiments, the tablet is manufactured using a method comprising direct compression.

[0410] In some embodiments, the tablet is manufactured using a method comprising dry granulation through slugging.

[0411] In some embodiments, the tablet is manufactured using a method comprising dry granulation through roller compaction.

[0412] Preferably, the tablet is manufactured using a method comprising dry granulation through roller compaction. Preferably the tablets of the invention are roller compacted tablets.

[0413] Typically, the tablets of the invention may be manufactured in a method comprising (i) blending alvelestat or a pharmaceutically acceptable salt thereof with one or more excipients (ii) granulation, (iii) a second blending process to form a power blend and (iv) compressing the powder blend into a tablet.Blending

[0414] In some embodiments, the method comprises blending alvelestat or a pharmaceutically acceptable salt thereof with excipients. In some embodiments, the alvelestat or a pharmaceutically acceptable salt thereof may be milled by any suitable method prior to blending with excipients.

[0415] The methods of manufacturing a tablet herein relate to the embodiments of the invention disclosed herein. Such a method may be used to make any of the embodiments of the invention, with the amounts of excipients to be used as specified for that embodiment.

[0416] The alvelestat or pharmaceutically acceptable salt thereof and the excipients may be blended by any suitable method in the preparation of tablets as disclosed herein.In some embodiments, all the excipients and / or alvelestat are blended at the same time. In other embodiments, the excipients and / or alvelestat may be blended in different orders or amounts, for example, in some embodiments certain excipients are blended first, and then are processed to form granules, before they are then blended with the remaining excipients to form the final power blend. In some embodiments of the blending process used in the production of tablets of the present invention, an amount of an excipient may be included in the initial blend that granules are formed from, and the rest of the excipient to be used in the tablet is blended in the post-granulation blending. In some embodiments the blending process may include milling of the alvelestat or a pharmaceutically acceptable salt thereof and / or the excipients of the tablet by any suitable method at one or more stages of the blending and granulation process.

[0417] In some embodiments, wherein the tablet comprises MCC, PVPcI and / or SSF, an amount of the MCC, PVPcI and / or SSF is blended prior to granulation. In some embodiments, wherein the tablet comprises MCC, PVPcI and / or SSF, an amount of the MCC, PVPcI and / or SSF is blended with the granules after granulation. In some embodiments, wherein the tablet comprises MCC, PVPcI and / or SSF, an amount of the MCC, PVPcI and / or SSF is blended prior to granulation, and an amount of the MCC, PVPcI and / or SSF is blended with the granules after granulation. In some embodiments, the method of manufacturing a tablet of the invention comprises blending an amount of the MCC, PVPcI and / or SSF prior to granulation, and blending an amount of the MCC, PVPcI and / or SSF with the granules after granulation.

[0418] In these embodiments, it is understood that the blending prior to granulation also includes alvelestat, or a pharmaceutically acceptable salt thereof, and the other intragranular excipients, and that the blending after granulation can also include other extragranular excipients.

[0419] In some embodiments, an amount of MCC is blended prior to granulation. In some embodiments, an amount of MCC is blended with the granules after granulation. In some embodiments, an amount of MCC is blended prior to granulation, and an amount of MCC is blended with the granules after granulation. In some embodiments, the method ofmanufacturing a tablet of the invention comprises blending an amount of MCC prior to granulation, and blending an amount of MCC with the granules after granulation.

[0420] In some embodiments, about 40 wt% to about 55 wt% (relative to the weight of the total components of the blend) of MCC is blended prior to granulation, and about 5 wt% to about 10 wt% (relative to the weight of the total components of the blend) of MCC is blended with the granules after granulation. In some embodiments, the method of manufacturing a tablet of the invention comprises blending 40 wt% to about 55 wt% (relative to the weight of the total components of the blend) of MCC prior to granulation and blending about 5 wt% to about 10 wt% (relative to the weight of the total components of the blend) of MCC with the granules after granulation.

[0421] In some embodiments, about 46 wt% (relative to the weight of the total components of the blend) of MCC is blended prior to granulation, and about 7 wt% (relative to the weight of the total components of the blend) of MCC is blended with the granules after granulation. In some embodiments, the method of manufacturing a tablet of the invention comprises blending 46 wt% (relative to the weight of the total components of the blend) of MCC prior to granulation, and blending about 7 wt% (relative to the weight of the total components of the blend) of MCC with the granules after granulation.

[0422] In some embodiments, about 53 wt% (relative to the weight of the total components of the blend) of MCC is blended prior to granulation, and about 7 wt% (relative to the weight of the total components of the blend) of MCC is blended with the granules after granulation. In some embodiments, the method of manufacturing a tablet of the invention comprises blending 53 wt% (relative to the weight of the total components of the blend) of MCC prior to granulation, and blending about 7 wt% (relative to the weight of the total components of the blend) of MCC with the granules after granulation.

[0423] In some embodiments, an amount of PVPcI is blended prior to granulation. In some embodiments, an amount of PVPcI is blended with the granules after granulation. In some embodiments, an amount of PVPcI is blended prior to granulation, and an amount of PVPcI is blended with the granules after granulation. In some embodiments, the method of manufacturing a tablet of the invention comprises blending an amount of PVPcI prior to granulation, and blending an amount of PVPcI with the granules after granulation.

[0424] In some embodiments, about 3.5 wt% to about 7 wt% (relative to the weight of the total components of the blend) of PVPcI is blended prior to granulation, and about 1 wt% to about 4 wt% (relative to the weight of the total components of the blend) of PVPcI is blended with the granules after granulation. In some embodiments, the method of manufacturing a tablet of the invention comprises blending about 3.5 wt% to about 7 wt%(relative to the weight of the total components of the blend) of PVPcI prior to granulation, and blending about 1 wt% to about 4 wt% (relative to the weight of the total components of the blend) of PVPcI with the granules after granulation.

[0425] In some embodiments, 7 wt% (relative to the weight of the total components of the blend) of PVPcI is blended prior to granulation, and 3 wt% (relative to the weight of the total components of the blend) of PVPcI is blended with the granules after granulation. In some embodiments, the method of manufacturing a tablet of the invention comprises blending 7 wt% (relative to the weight of the total components of the blend) of PVPcI prior to granulation, and blending about 3 wt% (relative to the weight of the total components of the blend) of PVPcI with the granules after granulation.

[0426] In some embodiments, an amount of SSF is blended prior to granulation. In some embodiments, an amount of SSF is blended with the granules after granulation. In some embodiments, an amount of SSF is blended prior to granulation, and an amount of SSF is blended with the granules after granulation. In some embodiments, the method of manufacturing a tablet of the invention comprises blending an amount of SSF prior to granulation, and blending an amount of SSF with the granules after granulation.

[0427] In some embodiments, about 1 wt% (relative to the weight of the total components of the blend) of SSF is blended prior to granulation, and about 0.5 wt% (relative to the weight of the total components of the blend) SSF is blended with the granules after granulation. In some embodiments, the method of manufacturing a tablet of the invention comprises blending about 1 wt% (relative to the weight of the total components of the blend) of SSF prior to granulation, and blending about 0.5 wt% (relative to the weight of the total components of the blend) of SSF with the granules after granulation.

[0428] In some embodiments, wherein the tablet comprises MCC, PVPcI and SSF, an amount of MCC, PVPcI and SSF is blended prior to granulation. In some embodiments, wherein the tablet comprises MCC, PVPcI and SSF, an amount of MCC, PVPcI and SSF is blended with the granules after granulation. In some embodiments, wherein the tablet comprises MCC, PVPcI and SSF, an amount of MCC, PVPcI and SSF is blended prior to granulation, and an amount of the MCC, PVPcI and SSF is blended with the granules after granulation. In some embodiments, the method of manufacturing a tablet of the invention comprises blending amounts of MCC, PVPcI and SSF prior to granulation, and blending further amounts of MCC, PVPcI and SSF with the granules after granulation.

[0429] In some embodiments, the method of manufacturing a tablet of the invention comprises blending about 40 wt% to about 55 wt% (relative to the weight of the totalcomponents of the blend) of MCC, about 3.5 wt% to about 7 wt% (relative to the weight of the total components of the blend) of PVPcI, and about 1 wt% (relative to the weight of the total components of the blend) of SSF prior to granulation, and blending about 5 wt% to about 10 wt% (relative to the weight of the total components of the blend) of MCC, about 1 wt% to about 4 wt% (relative to the weight of the total components of the blend) of PVPcI, and about 0.5 wt% (relative to the weight of the total components of the blend) SSF with the granules after granulation.

[0430] In some embodiments, the method of manufacturing a tablet of the invention comprises blending about 46 wt% (relative to the weight of the total components of the blend) of MCC, about 7 wt% (relative to the weight of the total components of the blend) of PVPcI, and about 1 wt% (relative to the weight of the total components of the blend) of SSF prior to granulation, and blending about 7 wt% (relative to the weight of the total components of the blend) of MCC, about 3 wt% (relative to the weight of the total components of the blend) of PVPcI, and about 0.5 wt% (relative to the weight of the total components of the blend) SSF with the granules after granulation.

[0431] In some embodiments, the method of manufacturing a tablet of the invention comprises blending about 53 wt% (relative to the weight of the total components of the blend) of MCC, about 7 wt% (relative to the weight of the total components of the blend) of PVPcI, and about 1 wt% (relative to the weight of the total components of the blend) of SSF are blended prior to granulation, and blending about 7 wt% (relative to the weight of the total components of the blend) of MCC, about 3 wt% (relative to the weight of the total components of the blend) of PVPcI, and about 0.5 wt% (relative to the weight of the total components of the blend) SSF with the granules after granulation.

[0432] In some embodiments, during the initial blending prior to granulation, an amount of an excipient, such as MCC, may be introduced along with alvelestat to the blending apparatus prior to the other excipients. The rest of the components to be included in the initial blend may then be introduced and blended together.Methods of treatment

[0433] The tablets disclosed herein may be used in methods of treatment of a disease mediated by a-1 antitrypsin deficiency. Thus, the invention provides a method for treating a patient with a disease mediated by a-1 antitrypsin deficiency, comprising administering the tablet of the invention to a patient in need thereof. In preferredembodiments, the disease mediated by a-1 antitrypsin deficiency is a disease of the respiratory system mediated by a-1 antitrypsin deficiency.

[0434] As used herein, a disease of the respiratory system which is mediated by a-1 antitrypsin deficiency includes asthma, including bronchial, allergic, intrinsic, extrinsic, exercise-induced, drug-induced (including aspirin and NSAID-induced) and dust-induced asthma, both intermittent and persistent and of all severities, and other causes of airway hyper-responsiveness; chronic obstructive pulmonary disease (COPD); bronchitis, including infectious and eosinophilic bronchitis; emphysema; bronchiectasis; cystic fibrosis; sarcoidosis; farmer's lung and related diseases; hypersensitivity pneumonitis; adult respiratory distress syndrome (ARDS); lung fibrosis, including cryptogenic fibrosing alveolitis, idiopathic interstitial pneumonias, fibrosis complicating anti-neoplastic therapy and chronic infection, including tuberculosis and aspergillosis and other fungal infections; complications of lung transplantation; antitussive activity including treatment of chronic cough associated with inflammatory and secretory conditions of the airways, and iatrogenic cough; acute and chronic rhinitis including rhinitis medicamentosa, and vasomotor rhinitis; perennial and seasonal allergic rhinitis including rhinitis nervosa (hay fever); nasal polyposis; acute viral infection including the common cold, pulmonary hypertension, and infection due to respiratory syncytial virus, influenza, coronavirus (including SARS) and adenovirus. In particular, the disease mediated by a-1 antitrypsin deficiency is COPD, emphysema, asthma, or bronchiectasis, in particular a-1 antitrypsin deficiency mediated emphysema.

[0435] Also provided is a method of treatment of a patient with COPD comprising administering the tablet of the invention to a patient in need thereof. Also provided is a method of treatment of a patient with emphysema comprising administering the tablet of the invention to a patient in need thereof. Also provided is a method of treatment of a patient with asthma comprising administering the tablet of the invention to a patient in need thereof. Also provided is a method of treatment of a patient with bronchiectasis comprising administering the tablet of the invention to a patient in need thereof.

[0436] Also provided are methods of treating or preventing graft rejection, cardiac allograft vasculopathy (CAV), cardiac allograft nephropathy (CAN), chronic lung allograft dysfunction (CLAD), bronchiolitis obliterans syndrome (BOS), lung transplant associated bronchiolitis obliterans syndrome (LT-BOS), graft versus host disease (GVHD), including acute graft versus host disease and chronic graft versus host disease.

[0437] Also provided are methods of treating or preventing a symptom or complication attributable of a SARS-COV infection, such as COVID-19. Such symptoms orcomplications may include acute respiratory distress syndrome (ARDS), acute lung injury (ALI). Systemic inflammatory response syndrome (SIRS), pulmonary fibrosis, pneumonia, inflammation of the lungs, respiratory failure (e.g. Type 1 or Type 2), coagulopathy, antiphospholipid syndrome (APS or APLS), multi-organ failure, cytokine release syndrome (CRS), dyspnea, shock, hypoxemia, neutrophilia, neurological complications, Guillain- Barre syndrome (GBS), and thrombosis.

[0438] Also provided are methods of treating or preventing fibrosis. In certain embodiments, the disease can be selected from graft rejection, graft versus host disease (GVHD), chronic lung allograft dysfunction (CLAD), Lung Transplant associated Bronchiolitis Obliterans Syndrome (LT-BOS), bronchiolitis obliterans syndrome (BOS), GVHD associated BOS (GVHD BOS), Lung Transplant associated Restrictive Allograft Syndrome (LT-RAS), GVHD associated restrictive chronic lung function decline (GVHD R- CLFD), liver disease, heart disease, cirrhosis, fibrothorax, radiation-induced lung injury, glial scar, arterial stiffness, kidney disease, Crohn’s disease, Dupuytren's contracture, keloid disorder, Peyronie's disease and adhesive capsulitis, rheumatoid arthritis, ulcerative colitis, systemic lupus erythematosus, and hypertension. In certain embodiments, the disease can be selected from non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatosis, non-alcoholic steatohepatitis (NASH), and cirrhosis.

[0439] The invention also provides a tablet of the invention for use in a method of treatment described above. The invention also provides alvelestat for use in a method of treatment described above, wherein the method comprises administering a tablet according to the invention to a patient in need thereof.Dosing

[0440] Typically, the tablets of the invention are administered orally. Thus, the tablets of the invention are typically suitable for oral administration.

[0441] In preferred embodiments, the tablets of the invention are administered twice daily.

[0442] In preferred embodiments, the tablets of the invention are administered twice daily and the total daily amount of alvelestat or a pharmaceutically salt thereof corresponds to 240 mg of alvelestat free base. In particular, the invention provides a method in which a tablet of the invention comprising alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to 120 mg alvelestat free base is administered to a patient twice daily. In particular, the invention provides a method in which two tablets of theinvention each comprising alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to 60 mg alvelestat free base are administered to a patient twice daily.

[0443] In preferred embodiments, the tablets of the invention are administered twice daily and the total daily amount of alvelestat or a pharmaceutically salt thereof corresponds to 480 mg of alvelestat free base. In particular, the invention provides a method in which two tablets of the invention comprising alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to 120 mg alvelestat free base are administered to a patient twice daily. In particular, the invention provides a method in which four tablets of the invention each comprising alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to 60 mg alvelestat free base are administered to a patient twice daily.

[0444] In some embodiments, a first daily dose is administered to the patient for a first time period, a second daily dose is administered to the patient for a second time period, a third daily dose is administered to the patient for a third time period, and a fourth daily dose is administered to the patient for a fourth time period. In some embodiments, the time periods may be the same or different. In some embodiments, the time periods may be 1 week or 2 weeks.

[0445] In some embodiments, the first daily dose is 60mg of alvelestat free base. In some embodiments, the first dose is given once daily. In some embodiments, the first dose is given as one 60 mg tablet.

[0446] In some embodiments, the second daily dose is 120mg of alvelestat free base. In some embodiments, the second dose is given once daily. In some embodiments, the first daily dose is given as one 120 mg tablet.

[0447] In some embodiments, the third daily dose is 180mg of alvelestat free base. In some embodiments, the third dose is given once daily. In some embodiments, the third daily dose is given as one 60 mg tablet and one 120 mg tablet or as three 60 mg tablets.

[0448] In some embodiments, the fourth daily dose is 240mg of alvelestat free base. In some embodiments, the fourth dose is given twice daily. In some embodiments, the fourth daily dose is given as one 120 mg twice a day or two 60 mg tablets twice a day.

[0449] In some embodiments, 60 mg of alvelestat free base is administered to the patient once daily for a first time period as a 60 mg tablet of the invention, 120 mg of alvelestat free base is administered to the patient for a second time period as a 120 mg tablet of the invention, 180 mg of alvelestat free base is administered to the patient to the patient for a third time period as a 60 mg tablet of the invention and a 120 mg tablet of theinvention, and 240 mg is administered to the patient as 120 mg twice daily, wherein the dose is given as one 120 mg tablet of the invention twice daily, for a fourth time period. In some embodiments, the time periods may be the same or different. In some embodiments, the time periods may be 1 week or 2 weeks.

[0450] In some embodiments, after the fourth time period, 120 mg of alvelestat free base is administered to the patient twice daily, wherein a total daily amount of 240 mg is administered to the patient.Remarks

[0451] It will be appreciated that where ranges of % weight are provided for different components of the composition of the core tablet, the total % weight of the components will add up to 100%. In particular, when the upper limits of each range, when added together, exceed 100%, it will be understood that the actual amounts of components present in the composition will be selected so that the total weight % totals 100% and does not exceed it.

[0452] As those skilled in the art will appreciate, numerous modifications and variations of the present disclosure are possible in light of these teachings, and all such are contemplated hereby.

[0453] For example, in addition to the embodiments described herein, the present disclosure contemplates and claims those disclosures resulting from the combination of features of the disclosure cited herein and those of the cited prior art references which complement the features of the present disclosure. Similarly, it will be appreciated that any described material, feature, or article may be used in combination with any other material, feature, or article, and such combinations are considered within the scope of this disclosure.

[0454] All publications, patents and patent applications are incorporated by reference in their entirety, as though individually incorporated by reference. The disclosure has been described with reference to various specific and embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the disclosure.EXAMPLESREFERENCE EXAMPLE 1 : impact of drug loading on manufacture and dissolution

[0455] The dissolution rate of alvelestat from formulations comprising different drug loads of alvelestat tosylate were compared.Part A

[0456] In particular, the dissolution rate (pH = 1, 75 rpm (0-60 minutes) + 200 rpm (> 60 minutes) of the tablet formulation used in phase 1 and 2a clinical studies comprising 10 wt% alvelestat tosylate (7.60 wt% alvelestat free base) was compared against the dissolution rate (pH = 2, 75rpm) for powder formulations in capsules comprising 15, 35 and 50 wt% alvelestat tosylate (11.4, 26.6 and 38.0 wt% of alvelestat free base respectively).

[0457] The results are shown in Figure 1A. The results indicated that higher amount of API (i.e. above 15 wt% alvelestat tosylate / 11.4 wt% alvelestat free base) in the formulation resulted in a dissolution of alvelestat tosylate that was too slow to be effective as an immediate release formulation, whereas the formulation with lower drug load displays a much faster dissolution rate.

[0458] These results show that the drug load influences dissolution rate, i.e. higher drug load results in a slower dissolution rate.

[0459] It was also found that manufacturability is influenced by the drug load. Higher drug load (>10 wt% alvelestat tosylate / 7.60 wt% alvelestat free base) resulted in a poorer manufacturability with respect to flowability and bulk density of the powder blend.Part B

[0460] The dissolution rate of coated tablets of the following drug loading of alvelestat tosylate was measured.Table 1 : drug loading of alvelestat in tablets tested for dissolution rates

[0461] The results are shown in Figure 1 B. This shows that the dissolution rates are slower at higher tablet strengths, ie, tablets with a higher API concentration gives a slower dissolution rate.Part C

[0462] Tablets comprising 30 mg alvelestat (as 39.5 mg alvelestat tosylate) with 10, 15 and 20 wt% alvelestat tosylate were prepared. A higher API concentration in the tablet affected the manufacturability negatively. Manufacturability of tablets with 20% API was poor. An API concentration of 15% compared to 10% increased the tablet weight variation due to a reduced flowability of the granules. An increase in drug load was thus judged not to be feasible.Conclusion

[0463] Therefore, a 10 wt% drug load of alvelestat tosylate was selected for manufacturing the 30 mg alvelestat dose tablet.REFERENCE EXAMPLE 2: dissolution of 30 mg dose strength tablets

[0464] For phase 1 and 2 studies, 30 mg dose immediate release tablets were produced. These tablets had the following composition. In particular, they comprise 9.88 wt% alvelestat tosylate, which corresponds to only 7.5 wt% alvelestat free base.Table 2: Formula A - 30 mg tablet compositiona. Weight of coating may vary between 3% to 5% of tablet core weight b. Pre-formulated commercially available blend - Opadry 03B28460 c. Removed (evaporation) during processing

[0465] These tablets were tested for their dissolution properties (USP Apparatus 2(Paddle), 900 mL, 50 mM sodium phosphate buffer pH 6.8, 75 rpm) and the results are shown in Figure 2.

[0466] It was thus possible to achieve fast release of alvelestat but a low drug load (<10 wt% alvelestat tosylate) was considered important for reliable manufacture and dissolution. However, such a low drug load was not ideal for higher dose strength tablets (e.g. 60 mg, 120 mg) required for phase 3 clinical study.EXAMPLE 1 : properties of alvelestat toyslate

[0467] Heckel analysis was performed using a Styl’OneTMEVO Compaction and Compression simulator (Korsch AG, Germany). Alvelestat tosyate was compacted to theoretical zero porosity using a single flat faced punch (11.28 mm).

[0468] The data generated was analysed to generate values for the True Density, Yield Pressure (Py) at high-speed and slow-speed compression and values for ‘out of die porosity’.

[0469] The Strain Rate Sensitivity (SRS) was calculated using the yield pressures determined at high-speed and slow-sped compression.

[0470] The bulk density and tapped bulk density for alvelestat tosylate was determined using standard methodology as described in US Pharmacopeia <616>, bulk density and tapped density of powders and then used to calculate the Carr index and Hausner ratio of alvelestat tosylate.

[0471] The physical properties of alvelestat tosylate are exemplified in the table below.Table 3: measured properties of alvelestat tosylate

[0472] The deformation behaviour of alvelestat is classified as ‘moderately hard - brittle’ material. The Carr Index and Hausner ratio indicate that alvelestat tosylate is classified as ‘very, very poor flow’. Taken together, the results indicate that alvelestat toyslate has powder properties that may be expected to make it difficult to formulate, particularly at higher drug loading than used in the 30 mg alvelestat tablets of Formula A used in clinical studies.EXAMPLE 2: manufacturing alvelestat tablets of the invention

[0473] Alvelestat tablets evaluated were manufactured using a dry granulation I tablet compression process, followed by optional film-coating.

[0474] The overall manufacturing process consisted of co-blending with excipients, sieving and mixing to produce a homogenous mixed powder blend followed by roller compaction and milling.

[0475] The intragranular excipients and alvelestat tosylate were co-blended prior to the dry granulation and the extragranular excipients were introduced afterwards. The lubricant, sodium stearyl fumarate was added, with the overall amount divided between the intra-granular blend and extra-granular stages. Optionally, microcrystalline cellulose and / or crospovidone were also divided between the intra-granular blend and extra-granular stages. The resulting granules (lubricated with extra-granular sodium stearyl fumarate) were then blended and compressed into core tablets.

[0476] Some of the tablets were subsequently film-coated.EXAMPLE 3: 120 mg tablets of the invention of different sizes

[0477] Tablet formulations were manufactured as set out in the table below using the general process set out in Example 2.

[0478] These formulations comprised 26.32 wt%, 19.74 wt% or 13.16 wt% alvelestat tosylate in 600 mg, 800 mg and 1200 mg tablets respectively (157.9 mg) corresponding to 20 wt%, 15% wt% and 10% wt% alvelestat free base respectively (120 mg).

[0479] Batches of the same composition, but making use of different batches of API, were labelled with a number representing the composition and a letter identifying which batch of API was used.

[0480] For tablet batches 1-4 and 6-9, batches marked as ‘a’ are from the same API batch, and batches with ‘b’ are from the other API batch (i.e. 1a and 2a share the same API batch, whereas 1a and 1b have different API batches).

[0481] For tablet batch 5, both 5a and 5b are from the ‘a’ batch of API, and c and d are from the ‘b’ batch of API.Table 4a: compositions of 600 mg 120 mg tabletsTable 4b: compositions of 800 mg 120 mg tabletsTable 4c: compositions of 1200 mg 120 mg tablets

[0482] The tablets produced were tested for alvelestat tosylate (Assay, % label claim), uniformity of content and by determining the amount of alvelestat tosylate in the tablets using gradient reversed phase liquid chromatography using a Acquity Waters HSS T3 column. Disintegration time was determined in water using harmonized methods and equipment as described in the US / European and Japanese Pharmacopoeia.Table 5: results from testing of compositions of Tables 4a-c above

[0483] 120 mg strength tablets can be manufactured with core tablet weights of 600 mg, 800 mg and 1200 mg. The Assay and Content Uniformity indicates that 120 mg tablets are manufacturable with acceptable tablet disintegration times.EXAMPLE 4: 120 mg tablets of the invention

[0484] Certain specific tablet formulations were manufactured with compositions as set out in the table below using the general process set out in Example 2.

[0485] These formulations comprised 26.32 wt% of alvelestat tosylate (157.9 mg), which corresponds to about 20 wt% of alvelestat free base (120 mg).Table 6: compositions of new 120 mg formulationEXAMPLE 5: dissolution of 120 mg tablets

[0486] Dissolution profiles of tablets according to the formulae A-C were prepared.

[0487] 30 mg tablets according to Formula A were tested using an automated sampling and analysis platform.

[0488] The dissolution profile of 120 mg uncoated tablets according to Formula B and C were determined in 900 mL of 50 mM sodium phosphate buffer at pH 6.8 and using aUSP apparatus 2 (paddle) at 75 rpm and 37± 0.5 °C. Analysis was made by UV spectrophotometer with a detection wavelength of 337 nm.

[0489] To confirm the dissolution of 120 mg as 4 x 30 mg tablets, tablet Batch 145 was tested for dissolution as a single 30 mg tablet and as 4 x 30 mg tablets. The hydrodynamic behaviour of 4 x 30 mg is not representative of the hydrodynamic behaviour of a single 120 mg strength tablet, but this test was run in order to aid understanding of the behaviour of an increased ‘load’ in the test. Fast dissolution was possible using 4 x 30 mg tablets.

[0490] As can be seen in Figure 3, similar dissolution profiles are produced under the same conditions as those for the 1x30 mg tablet, showing that there is sufficient dissolution of alvelestat even with the higher drug loading, contrary to the expectations from earlier testing of the API.EXAMPLE 6: further formulations of 120 mg tablets

[0491] Further formulations were explored, and uncoated 120 mg tablets according to the formulae below were produced.Table 7: further 120 mg tablet compositions

[0492] Formula D differs from Formula C by the presence of extragranular crospovidone, and formula E differs from formula D by the presence of extragranular microcrystalline cellulose.

[0493] Dissolution tests showing the effect of the extragranular addition of crospovidone on the initial dissolution rate (0-10 minutes) were determined in 900 mL of 50 mM sodium phosphate buffer at pH 6.8 using a USP apparatus 2 (paddle) at 75 rpm and 37± 0.5 °C. Analysis was made by UV spectrophotometer with a detection wavelength of 337 nm. Disintegration time was determined in water using harmonized methods and equipment as described in the US / European and Japanese Pharmacopoeia.

[0494] The impact of dividing the crospovidone between the intragranular and extragranular stages is shown in the table below.Table 8: disintegration and dissolution rates measured to compare Formula C to Formula D

[0495] As can be seen in the table above, dividing the crospovidone that would normally be added to the intragranular stage between the intragranular and extragranular stages does not significantly influence the maximum disintegration time but surprisingly improves the initial rate of dissolution of the 120 mg and 60 mg strength tablets.

[0496] Using the same method as above, dissolution was also measured for tablets of formula E.Table 9: disintegration and dissolution rates measured to compare Formula D to Formula E

[0497] As can be seen in the table above tablets according to formula E improve the initial rate of dissolution of the 120 mg and 60 mg strength tablets yet further compared to tablets according to formula D. This shows that the extragranular addition of MCC results in improved dissolution.

[0498] The dissolution profiles of tablets according to Formulae D and E were measured, according to the same method set out above, and the results are shown in Figures 4A and 4B. Figure 4B shows that the tablets according to these formulae fall within the range of dissolution of tablets of Formula A.EXAMPLE 7: dissolution of 120 mg tablets at different pHs

[0499] The dissolution profiles of uncoated tablets of the invention of Formula E comprising 120 mg alvelestat were determined at pH 6.8 (phosphate buffer, 100 rpm) and pH 1.1 (HCI, 100 rpm). The results are shown in Figure 5 and are shown to fall within the dissolution range of coated 30 mg tablets used in clinical trials, when tested at pH 6.8, rpm:75.

[0500] These data show that tablets of the invention display a favourable dissolution profile at both pH 6.8 and 1.1.EXAMPLE 8: 60 mg tablets of the invention

[0501] Certain specific tablet formulations were manufactured with compositions as set out in the table below using the general process set out in Example 2.

[0502] These formulations comprised 79 mg of alvelestat tosylate, which corresponds to 60 mg of alvelestat free base.Table 10: compositions of 60 mg tablets

[0503] As for the tablets according to formulae C-E in Example 6, further dissolution tests were run on the 60 mg tablets of formulae F-H. Table 11a: disintegration and dissolution rates measured to compare Formula F to Formula GTable 11b: disintegration and dissolution rates measured to compare Formula G to Formula H

[0504] These results also confirm the effect of extragranular crospovidone and microcrystalline cellulose as shown in Example 6.

[0505] Dissolution profiles for Formulae G and H are shown in Figures 6A and 6B. Figure 6B shows that the dissolution of tablets according to these formulae fall within the range of dissolution of tablets of Formula A.EXAMPLE 9: further 60 mg tablet composition

[0506] Another 60 mg tablet was also prepared according to the process set out in Example 2. The composition of this tablet is set out below.Table 12: composition of 60 mg tablet according to formula IEXAMPLE 10: coated tablets and further dissolution tests on 60 mg and 120 mg tablets

[0507] The 60 mg coated tablets were coated with Opadry 03B28460 (white) and the120 coated tablet were coated with Opadry 03F230007 (peach). 4 wt% of coating was applied to each, i.e. 12 mg of coating for the 300 mg 60 mg tablet, 16 mg of coating for the 400 mg 60 mg tablet, and 24 mg of coating for the 600 mg 120 mg tablet.

[0508] Compositions of the coatings are set out below. Table 13a: coating composition for 120 mg tabletsTable 13b: coating composition for 60 mg tablets

[0509] Dissolution tests were performed on coated 60 mg tablets according to Formula H. Further dissolution tests were performed on 120 mg tablets according to Formula E and 60 mg tablets according to Formula I, where uncoated and coated tablets were tested. These tests were run using either a phosphate buffer of pH 6.8 or HCI pH 1.1, using the same method as described in example 5, except that the rotation speed was increased to 100 rpm.

[0510] The results of these tests can be seen in Figures 7A-7C. These data show that both coated and uncoated tablets of the invention display a favourable dissolution profile at both pH 6.8 and 1.1.EXAMPLE 11 : coated tablets and dissolution tests against Formula A1

[0511] Alvelestat tablets according to Formula A1, I and E were manufactured using the same batch of alvelestat, according to the process of Example 2.

[0512] The overall manufacturing process consisted of co-blending with excipients, sieving and mixing to produce a homogenous mixed powder blend followed by roller compaction and milling. The lubricant, sodium stearyl fumarate was added, with the overall amount divided between the intragranular blend and extragranular stages. The resulting granules (lubricated with extra-granular sodium stearyl fumarate) were then blended and compressed into core tablets (600 mg core weight for Formula E and 400 mg core weight for tablets of Formula A1 and Formula I) and were then film coated using an aqueous film coat suspension. Tablets of Formula I and Formula E were manufactured with the microcrystalline cellulose and crospovidone split between the intragranular and extragranular stages.Table 14a: Formula A1

[0513] Formula A1 comprised 39.5 mg of alvelestat tosylate, which corresponds to 30 mg of alvelestat free base.

[0514] The coating for tablets according to Formulae A1 and I was Opadry 03B28460. For tablets according to Formula E, Opadry 03F230007 was used for the coating. Table 14b: film coating of tablets being assessed

[0515] Dissolution was analysed under identical conditions: 1000 mL of 50 mM sodium phosphate buffer pH 6.8, using USP apparatus 2 (paddle), 37± 0.5 °C using mixing speed 100 rpm. Analysis was made by UV spectrophotometer with a detection wavelength of 337 nm. The dissolution after 60 minutes is shown in the table below:Table 14c: Comparability of dissolution

[0516] The 60 mg and 120 mg strength film-coated tablets showed an improvement in the overall release of alvelestat compared to the 30 mg strength film-coated tablets, achieving the release of 100% and 95% of label claim compared to 91% label claim for the 30 mg strength tablets.EXAMPLE 12: mass production tests of tablets

[0517] The manufacturing process for Alvelestat 60 mg strength (Formula I) and 120 mg strength (Formula E) film coated tablets was performed to produce -20,000 and - 60,000 tablets per batch manufactured respectively.

[0518] Manufacturing was carried out following Good Manufacturing Practice (GMP) in a GMP manufacturing facility. Dissolution was analysed under identical conditions: 1000 mL of 50 mM sodium phosphate buffer pH 6.8, using USP apparatus 2 (paddle), 37± 0.5 °C using mixing speed 100 rpm. Analysis was made by UV spectrophotometer with a detection wavelength of 337 nm. The dissolution specification for Quality Control release was ‘not less than 80% (Q) of label claim after 45 minutes’.

[0519] Alvelestat ‘Assay’ was determined using high performance liquid chromatography (HPLC: reversed phase liquid chromatography procedure using a high- strength silica trifunctionally-bonded C18 column with ultraviolet (UV) detection at 240 nm using UV or Diode Array Detection using a mobile phase of acetonitrile and phosphate buffer). Tablet Uniformity of Content was determined in accordance with United States Pharmacopeia (USP) <905> and European Pharmacopeia (Ph. Eur.) 2.9.40 with sample preparation followed by quantification using HPLC. All the analytical procedures had been previously validated. The dissolution, assay and uniformity of content results are shown in the table below.Table 15: Dissolution, Assay and Uniformity of Content of film coated alvelestat tablets manufactured at large scaleL1 AV = Acceptance value to be compared to the maximum allowed acceptance value (L1).

[0520] For solid dosage forms, the maximum allowed acceptance value (L1) is 15.0. The acceptance values (AV) for these tablets are 1.8, 2.0 and 2.4, and so are well away from failure at L1 = 15.

[0521] Alvelestat 60 mg strength and 120 mg strength film coated tablets can be manufactured at large scale with good dissolution which is within specification i.e. tablets are produced of uniform content, show an alvelestat assay at 100% label claim, and have dissolution well above 80% at 45 minutes.The embodiments set out below represent examples of embodiments of the invention.1. A tablet comprising alvelestat or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients; and wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 10 wt% of alvelestat free base; and wherein the tablet comprises an amount of alvelestat or a pharmaceutically acceptable salt thereof that corresponds to about 60 mg to about 120 mg of alvelestat free base.2. A tablet according to embodiment 1 , wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 15 wt% of alvelestat free base and at most about 40 wt% of alvelestat free base.3. A tablet according to any previous embodiment, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 15 wt% of alvelestat free base and at most about 25 wt% of alvelestat free base.4. A tablet according to any previous embodiment, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base.5. A tablet according to any one of embodiments 1 to 3, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 15 wt% of alvelestat free base.6. A tablet according to any previous embodiment, wherein the alvelestat or a pharmaceutically acceptable salt thereof is in the form of alvelestat tosylate.7. A tablet according to any previous embodiment wherein the tablet comprises at least one pharmaceutically acceptable excipient that acts as a filler.8. A tablet according to any previous embodiment wherein the tablet comprises at least one pharmaceutically acceptable excipient that acts as a disintegrant.9. A tablet according to any previous embodiment wherein the tablet comprises at least one pharmaceutically acceptable excipient that acts as a surfactant.10. A tablet according to any previous embodiment wherein the tablet comprises at least one pharmaceutically acceptable excipient that acts as a lubricant.11. A tablet according to any previous embodiment wherein the tablet comprises microcrystalline cellulose (MCC).12. A tablet according to any previous embodiment, wherein the tablet comprises at most about 70 wt% MCC.13. A tablet according to any previous embodiment, wherein the tablet comprises at least about 40 wt% MCC and at most about 70 wt% MCC.14. A tablet according to any previous embodiment, wherein the tablet comprises at least about 45 wt% MCC and at most about 65 wt% MCC.15. A tablet according to any previous embodiment, wherein the tablet comprises at least about 50 wt % MCC and at most about 62 wt% MCC.16. A tablet according to any previous embodiment wherein the tablet comprises crosslinked polyvinylpyrrolidone (PVPcI).17. A tablet according to embodiment 16, wherein the tablet further comprises microcrystalline cellulose (MCC), and wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is from about 1 :3 to about 1 :15.18. A tablet according to embodiment 17 wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is from about 1 :4 to about 1 :12.19. A tablet according to any previous embodiment, wherein the tablet comprises at least about 3 wt% PVPcI.20. A tablet according to any previous embodiment, wherein the tablet comprises at least about 3 wt% PVPcI and at most about 15 wt% PVPcI.21. A tablet according to any previous embodiment, wherein the tablet comprises at least about 4.5 wt % PVPcI and at most about 11 wt% PVPcI.22. A tablet according to any previous embodiment wherein the tablet comprises sodium lauryl sulfate (SLS).23. A tablet according to any previous embodiment, wherein the tablet comprises at least about 0.5 wt% SLS.24. A tablet according to any previous embodiment, wherein the tablet comprises at least about 0.5 wt% SLS and at most about 2.5 wt% SLS.25. A tablet according to any previous embodiment, wherein the tablet comprises at least about 1.1 wt % SLS and at most about 2.2 wt% SLS.26. A tablet according to any previous embodiment wherein the tablet comprises Calcium Hydrogen Phosphate Dihydrate (DCP).27. A tablet according to any previous embodiment wherein the tablet comprises at most about 10 wt% DCP.28. A tablet according to any previous embodiment wherein the tablet comprises at least about 5 wt% DCP and at most about 10 wt% DCP.29. A tablet according to any previous embodiment wherein the tablet comprises sodium stearyl fumarate (SSF).30. A tablet according to any previous embodiment wherein the tablet comprises at least about 0.5 wt% SSF and at most about 2 wt% SSF.31. A tablet according to any previous embodiment wherein the tablet comprises:(i) alvelestat or a pharmaceutically acceptable salt thereof;(ii) MCC;(iii) PVPcI; and(iv) SLS.32. A tablet according to embodiment 31 wherein the tablet further comprises DCP and SSF.33. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC; and(ii) at least about 3 wt% and at most about 15 wt% PVPcI.34. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC; and(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI.35. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC; and(ii) at least about 0.5 wt% and at most about 2.5 wt% SLS.36. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC; and(ii) at least about 1.1 wt % and at most about 2.2 wt% SLS.37. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC; and(ii) at least about 3 wt% and at most about 15 wt% PVPcI.38. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC; and(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI.39. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC; and(ii) at least about 0.5 wt% and at most about 2.5 wt% SLS.40. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC; and(ii) at least about 1.1 wt % and at most about 2.2 wt% SLS.41. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt% and at most about 62 wt% MCC; and(ii) at least about 3 wt% and at most about 15 wt% PVPcI.42. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt% and at most about 62 wt% MCC; and(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI.43. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt% and at most about 62 wt% MCC; and(ii) at least about 0.5 wt% and at most about 2.5 wt% SLS.44. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt% and at most about 62 wt% MCC; and(ii) at least about 1.1 wt % and at most about 2.2 wt% SLS.45. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(ii) at least about 3 wt% and at most about 15 wt% PVPcI.46. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(ii) at least about 3 wt% and at most about 15 wt% PVPcI.47. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI.48. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI.49. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.50. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.51. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.52. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.53. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.54. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.55. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.56. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.57. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.58. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.59. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.60. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.61. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt % and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.62. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.63. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.64. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.65. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.66. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.67. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.68. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.69. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.70. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.71. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.72. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.73. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt % and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.74. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.75. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.76. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.77. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.78. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.79. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.80. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.81. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.82. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP;(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.83. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.84. A tablet according to any previous embodiment, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.85. A tablet according to any previous embodiment wherein the tablet comprises about 53 wt % MCC or about 60 wt% MCC.86. A tablet according to any previous embodiment wherein the tablet comprises about 10 wt% PVPcI.87. A tablet according to any previous embodiment wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is about 1:5 or about 1:6.88. A tablet according to any previous embodiment wherein the tablet comprises about 2 wt% SLS.A tablet according to any previous embodiment wherein the tablet comprises about 7 wt% DCP. A tablet according to any previous embodiment wherein the tablet comprises about1.5 wt% SSF. A tablet according to any previous embodiment wherein the tablet comprises about 53 wt % MCC and about 10 wt% PVPcI. A tablet according to any previous embodiment wherein the tablet comprises about 53 wt % MCC and about 2 wt% SLS. A tablet according to any previous embodiment wherein the tablet comprises about 10 wt% PVPcI and about 2 wt% SLS. A tablet according to any previous embodiment wherein the tablet comprises about 53 wt % MCC, about 10 wt% PVPcI and about 2 wt% SLS. A tablet according to any previous embodiment wherein the tablet comprises about53.4 wt % MCC, about 10 wt% PVPcI, about 2.0 wt% SLS, about 6.8 wt% DCP, about1.5 wt% SSF and wherein the amount of alvelestat or a pharmaceutically acceptable salt thereof is about 26.3 wt% alvelestat tosylate. A tablet according to any one of embodiments 1 to 91 wherein the tablet comprises about 60 wt % MCC and about 10 wt% PVPcI. A tablet according to any one of embodiments 1 to 91 or embodiment 96 wherein the tablet comprises about 60 wt % MCC and about 2 wt% SLS. A tablet according to any one of embodiments 1 to 91 or embodiments 96-97 wherein the tablet comprises about 10 wt% PVPcI and about 2 wt% SLS. A tablet according to any one of embodiments 1 to 91 or embodiments 96-98 wherein the tablet comprises about 60 wt % MCC, about 10 wt% PVPcI and about 2 wt% SLS. A tablet according to any one of embodiments 1 to 91 or embodiments 96-99 wherein the tablet comprises about 59.9 wt % MCC, about 10 wt% PVPcI, about 2.0wt% SLS, about 6.8 wt% DCP, about 1.5 wt% SSF and wherein the amount of alvelestat or a pharmaceutically acceptable salt thereof is about 19.7 wt% alvelestat tosylate.101. A tablet according to any previous embodiment wherein the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to about 60 mg, about 80 mg, or about 120 mg of alvelestat free base.102. A tablet according to embodiment 101 wherein the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to about 120 mg of alvelestat free base.103. A tablet according to embodiment 101 wherein the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to about 60 mg of alvelestat free base.104. A tablet according to embodiment 102 comprising about 158 mg alvelestat tosylate.105. A tablet according to embodiment 103 comprising about 79 mg alvelestat tosylate.106. A tablet according to any previous embodiment wherein the weight of the tablet is between about 300 mg to about 1200 mg.107. A tablet according to embodiment 106 wherein the weight of the tablet is about 600 mg.108. A tablet according to embodiment 106 wherein the weight of the tablet is about 400 mg.109. The tablet according to any previous embodiment, wherein the tablet is coated with a film coating.110. A tablet comprising alvelestat or a pharmaceutically acceptable salt thereof, wherein the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to about 120 mg of alvelestat free base; and wherein the tablet comprises one or more pharmaceutically acceptable excipients.111. A tablet according to embodiment 110, wherein the alvelestat or a pharmaceutically acceptable salt thereof is in the form of alvelestat tosylate.112. A tablet according to any one of embodiments 110-111 , wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 10 wt% of alvelestat free base.113. A tablet according to any one of embodiments 110-112, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 15 wt% of alvelestat free base and at most about 40 wt% of alvelestat free base.114. A tablet according to any one of embodiments 110-113, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 15 wt% of alvelestat free base and at most about 25 wt% of alvelestat free base.115. A tablet according to any one of embodiments 110-114, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base.116. A tablet according to any one of embodiments 110-115 wherein the tablet comprises at least one pharmaceutically acceptable excipient that acts as a filler.117. A tablet according to any one of embodiments 110-116 wherein the tablet comprises at least one pharmaceutically acceptable excipient that acts as a disintegrant.118. A tablet according to any one of embodiments 110-117 wherein the tablet comprises at least one pharmaceutically acceptable excipient that acts as a surfactant.119. A tablet according to any one of embodiments 110-118 wherein the tablet comprises at least one pharmaceutically acceptable excipient that acts as a lubricant.120. A tablet according to any one of embodiments 110-119 wherein the tablet comprises microcrystalline cellulose (MCC).121. A tablet according to any one of embodiments 110 to 120, wherein the tablet comprises at most about 70 wt% MCC.122. A tablet according to any one of embodiments 110 to 121, wherein the tablet comprises at least about 40 wt% MCC and at most about 70 wt% MCC.123. A tablet according to any one of embodiments 110 to 122, wherein the tablet comprises at least about 45 wt% MCC and at most about 65 wt% MCC.124. A tablet according to any one of embodiments 110 to 123, wherein the tablet comprises at least about 50 wt % MCC and at most about 60 wt% MCC.125. A tablet according to any one of embodiments 110 to 124, wherein the tablet comprises polyvinylpyrrolidone (PVPcI).126. A tablet according to embodiment 125, wherein the tablet further comprises microcrystalline cellulose (MCC), and wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is from about 1 :3 to about 1 :15.127. A tablet according to embodiment 126 wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is from about 1:4 to about 1:12.128. A tablet according to any one of embodiments 110 to 127, wherein the tablet comprises at least about 3 wt% PVPcI.129. A tablet according to any one of embodiments 110 to 128, wherein the tablet comprises at least about 3 wt% PVPcI and at most about 15 wt% PVPcI.130. A tablet according to any one of embodiments 110 to 129, wherein the tablet comprises at least about 4.5 wt % PVPcI and at most about 11 wt% PVPcI.131. A tablet according to any one of embodiments 110 to 130, wherein the tablet comprises sodium lauryl sulfate (SLS).132. A tablet according to any one of embodiments 110 to 131, wherein the tablet comprises at least about 0.5 wt% SLS.133. A tablet according to any one of embodiments 110 to 132, wherein the tablet comprises at least about 0.5 wt% SLS and at most about 2.5 wt% SLS.134. A tablet according to any one of embodiments 110 to 133, wherein the tablet comprises at least about 1.1 wt % SLS and at most about 2.2 wt% SLS.135. A tablet according to any one of embodiments 110 to 134, wherein the tablet comprises Calcium Hydrogen Phosphate Dihydrate (DCP).136. A tablet according to any one of embodiments 110 to 135, wherein the tablet comprises at most about 10 wt% DCP.137. A tablet according to any one of embodiments 110 to 136, wherein the tablet comprises at least about 5 wt% DCP and at most about 10 wt% DCP.138. A tablet according to any one of embodiments 110 to 137 wherein the tablet comprises sodium stearyl fumarate (SSF).139. A tablet according to any one of embodiments 110 to 138, wherein the tablet comprises at least about 0.5 wt% SSF and at most about 2 wt% SSF.140. A tablet according to any one of embodiments 110 to 139, wherein the tablet comprises:(i) alvelestat or a pharmaceutically acceptable salt thereof;(ii) MCC;(iii) PVPcI; and(iv) SLS.141. A tablet according to embodiment 140 wherein the tablet further comprises DCP and SSF.142. A tablet according to any one of embodiments 110 to 141, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC; and(ii) at least about 3 wt% and at most about 15 wt% PVPcI.143. A tablet according to any one of embodiments 110 to 142, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC; and(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI.144. A tablet according to any one of embodiments 110 to 143, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC; and(ii) at least about 0.5 wt% and at most about 2.5 wt% SLS.145. A tablet according to any one of embodiments 110 to 144, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC; and(ii) at least about 1.1 wt % and at most about 2.2 wt% SLS.146. A tablet according to any one of embodiments 110 to 145, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC; and(ii) at least about 3 wt% and at most about 15 wt% PVPcI.147. A tablet according to any one of embodiments 110 to 146, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC; and(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI.148. A tablet according to any one of embodiments 110 to 147, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC; and(ii) at least about 0.5 wt% and at most about 2.5 wt% SLS.149. A tablet according to any one of embodiments 110 to 148, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC; and(ii) at least about 1.1 wt % and at most about 2.2 wt% SLS.150. A tablet according to any one of embodiments 110 to 149, wherein the tablet comprises:(i) at least about 50 wt% and at most about 60 wt% MCC; and(ii) at least about 3 wt% and at most about 15 wt% PVPcI.151. A tablet according to any one of embodiments 110 to 150, wherein the tablet comprises:(i) at least about 50 wt% and at most about 60 wt% MCC; and(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI.152. A tablet according to any one of embodiments 110 to 151, wherein the tablet comprises:(i) at least about 50 wt% and at most about 60 wt% MCC; and(ii) at least about 0.5 wt% and at most about 2.5 wt% SLS.153. A tablet according to any one of embodiments 110 to 152, wherein the tablet comprises:(i) at least about 50 wt% and at most about 60 wt% MCC; and(ii) at least about 1.1 wt % and at most about 2.2 wt% SLS.154. A tablet according to any one of embodiments 110 to 153, wherein the tablet comprises:(i) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(ii) at least about 3 wt% and at most about 15 wt% PVPcI.155. A tablet according to any one of embodiments 110 to 154, wherein the tablet comprises:(i) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(ii) at least about 3 wt% and at most about 15 wt% PVPcI.156. A tablet according to any one of embodiments 110 to 155, wherein the tablet comprises:(i) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI.157. A tablet according to any one of embodiments 110 to 156, wherein the tablet comprises:(i) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI.158. A tablet according to any one of embodiments 110 to 157, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.159. A tablet according to any one of embodiments 110 to 158, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.160. A tablet according to any one of embodiments 110 to 159, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.161. A tablet according to any one of embodiments 110 to 160, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.162. A tablet according to any one of embodiments 110 to 161, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.163. A tablet according to any one of embodiments 110 to 162, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.164. A tablet according to any one of embodiments 110 to 163, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.165. A tablet according to any one of embodiments 110 to 164, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.166. A tablet according to any one of embodiments 110 to 165, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.167. A tablet according to any one of embodiments 110 to 166, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.168. A tablet according to any one of embodiments 110 to 167, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS.169. A tablet according to any one of embodiments 110 to 168, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.170. A tablet according to any one of embodiments 110 to 169, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt % and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.171. A tablet according to any one of embodiments 110 to 170, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.172. A tablet according to any one of embodiments 110 to 171, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.173. A tablet according to any one of embodiments 110 to 172, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.174. A tablet according to any one of embodiments 110 to 173, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.175. A tablet according to any one of embodiments 110 to 174, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.176. A tablet according to any one of embodiments 110 to 175, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.177. A tablet according to any one of embodiments 110 to 176, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.178. A tablet according to any one of embodiments 110 to 177, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.179. A tablet according to any one of embodiments 110 to 178, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.180. A tablet according to any one of embodiments 110 to 179, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.181. A tablet according to any one of embodiments 110 to 180, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP.182. A tablet according to any one of embodiments 110 to 181, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt % and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.183. A tablet according to any one of embodiments 110 to 182, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.184. A tablet according to any one of embodiments 110 to 183, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.185. A tablet according to any one of embodiments 110 to 184, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.186. A tablet according to any one of embodiments 110 to 185, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.187. A tablet according to any one of embodiments 110 to 186, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.188. A tablet according to any one of embodiments 110 to 187, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.189. A tablet according to any one of embodiments 110 to 188, wherein the tablet comprises:(i) at least about 45 wt% and at most about 65 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.190. A tablet according to any one of embodiments 110 to 189, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.191. A tablet according to any one of embodiments 110 to 190, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP;(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.192. A tablet according to any one of embodiments 110 to 191, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.193. A tablet according to any one of embodiments 110 to 192, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.194. A tablet according to any one of embodiments 110 to 193 wherein the tablet comprises about 53 wt % MCC.195. A tablet according to any one of embodiments 110 to 194 wherein the tablet comprises about 10 wt% PVPcI.196. A tablet according to any one of embodiments 110 to 195 wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is about 1:5.197. A tablet according to any one of embodiments 110 to 196 wherein the tablet comprises about 2 wt% SLS.198. A tablet according to any one of embodiments 110 to 197 wherein the tablet comprises about 53 wt % MCC and about 10 wt% PVPcI.199. A tablet according to any one of embodiments 110 to 198 wherein the tablet comprises about 53 wt % MCC and about 2 wt% SLS.200. A tablet according to any one of embodiments 110 to 199 wherein the tablet comprises about 10 wt% PVPcI and about 2 wt% SLS.201. A tablet according to any one of embodiments 110 to 200 wherein the tablet comprises about 53 wt % MCC, about 10 wt% PVPcI and about 2 wt% SLS.202. A tablet according to any one of embodiments 110 to 201 wherein the tablet comprises about 7 wt% DCP.203. A tablet according to any one of embodiments 110 to 202 wherein the tablet comprises about 1.5 wt% SSF.204. A tablet according to any one of embodiments 110 to 203 wherein the tablet comprises about 53.4 wt % MCC, about 10 wt% PVPcI, about 2.0 wt% SLS, about 6.8 wt% DCP, about 1.5 wt% SSF and wherein the amount of alvelestat or a pharmaceutically acceptable salt thereof comprises about 26.3 wt% alvelestat tosylate.205. A tablet according to any one of embodiments 110 to 204 comprising about 158 mg alvelestat tosylate.206. A tablet according to any one of embodiments 110 to 205 wherein the weight of the tablet is between about 500 mg to about 1200 mg.207. A tablet according to any one of embodiments 110 to 206 wherein the weight of the tablet is about 600 mg.208. A tablet according to any one of embodiments 110 to 207 wherein the tablet is coated with a film coating.209. A tablet according to any preceding embodiment wherein the tablet comprises about 7 wt% MCC extragranularly.210. A tablet according to any preceding embodiment wherein the tablet comprises about 3 wt% PVPcI extragranularly.211. A tablet according to any preceding embodiment wherein the tablet comprises about 7 wt% MCC and about 3 wt% PVPcI extragranularly.212. A tablet according to any preceding embodiment wherein the tablet comprises about 7 wt% MCC, about 3 wt% PVPcI and about 0.5 wt% SSF extragranularly.213. A method of treatment of a disease which is mediated by a-1 antitrypsin deficiency wherein the method comprises administering one or more tablet(s) according to any preceding embodiment to a subject in need thereof.214. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method of treatment of a disease which is mediated by a-1 antitrypsin deficiency wherein the method comprises administering one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof.215. The method of embodiment 213 or the alvelestat for use of embodiment 214, wherein the disease mediated by a-1 antitrypsin deficiency is COPD, emphysema, asthma or bronchiectasis, in particular AATD-mediated emphysema.A method of treating or preventing graft rejection, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof. A method of treating or preventing graft versus host disease (GVHD), wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof. A method of treating or preventing lung transplant associated bronchiolitis obliterans syndrome, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof. A method of treating or preventing bronchiolitis obliterans syndrome (BOS) associated with GVHD, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method of treating or preventing graft rejection, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method of treating or preventing graft versus host disease (GVHD), wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method of treating or preventing lung transplant associated bronchiolitis obliterans syndrome, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to anyone of embodiments 1 to 212 to a subject in need thereof.223. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method of treating or preventing bronchiolitis obliterans syndrome (BOS) associated with GVHD, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof.224. A method for treating a coronavirus infection and / or preventing progression of a coronavirus disease, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof.225. A method for treating or preventing a lung or respiratory condition in a subject having a coronavirus infection, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof.226. A method for treating and / or preventing progression of COVID-19, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof.227. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method for treating a coronavirus infection and / or preventing progression of a coronavirus disease, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof.228. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing a lung or respiratory condition in a subject having a coronavirus infection, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according any one of embodiments 1 to 212 to a subject in need thereof.Alvelestat or a pharmaceutically acceptable salt thereof for use in a method for treating and / or preventing progression of COVID- 19, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof. A method for treating or preventing bronchiectasis, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing bronchiectasis, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of embodiments 1 to 212 to a subject in need thereof.

Claims

CLAIMS1. A tablet comprising alvelestat or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable excipients; and wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 10 wt% of alvelestat free base; and wherein the tablet comprises an amount of alvelestat or a pharmaceutically acceptable salt thereof that corresponds to about 60 mg to about 120 mg of alvelestat free base.

2. A tablet according to claim 1 , wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 15 wt% of alvelestat free base and at most about 40 wt% of alvelestat free base, for example, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 15 wt% of alvelestat free base and at most about 25 wt% of alvelestat free base, for example, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% or 15 wt% of alvelestat free base.

3. A tablet according to any previous claim, wherein the alvelestat or a pharmaceutically acceptable salt thereof is in the form of alvelestat tosylate.

4. A tablet according to any previous claim wherein the tablet comprises:(i) at least one pharmaceutically acceptable excipient that acts as a filler; and / or(ii) at least one pharmaceutically acceptable excipient that acts as a disintegrant; and / or(iii) at least one pharmaceutically acceptable excipient that acts as a surfactant; and / or(iv) at least one pharmaceutically acceptable excipient that acts as a lubricant.

5. A tablet according to any previous claim wherein the tablet comprises:(a) microcrystalline cellulose (MCC), for example wherein the tablet comprises at least about 40 wt% MCC and at most about 70 wt% MCC, for example at least about 50 wt % MCC and at most about 62 wt% MCC; and / or(b) cross-linked polyvinylpyrrolidone (PVPcI), optionally wherein:(i) the tablet further comprises microcrystalline cellulose (MCC), and wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is from about 1 :3 to about 1 : 15, for example, wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is from about 1 :4 to about 1 :12; and / or(ii) the tablet comprises at least about 3 wt% PVPcI and at most about 15 wt% PVPcI, for example, wherein the tablet comprises at least about 4.5 wt % PVPcI and at most about 11 wt% PVPcI; and / or(c) sodium lauryl sulfate (SLS), for example, wherein the tablet comprises at least about 0.5 wt% SLS and at most about 2.5 wt% SLS, for example, at least about 1.1 wt % SLS and at most about 2.2 wt% SLS; and / or(d) Calcium Hydrogen Phosphate Dihydrate (DCP), for example, wherein the tablet comprises at least about 5 wt% DCP and at most about 10 wt% DCP; and / or(e) sodium stearyl fumarate (SSF), for example, wherein the tablet comprises at least about 0.5 wt% SSF and at most about 2 wt% SSF.

6. A tablet according to any previous claim wherein the tablet comprises:(i) alvelestat or a pharmaceutically acceptable salt thereof;(ii) MCC;(iii) PVPcI; and(iv) SLS; optionally, wherein the tablet further comprises DCP and SSF.

7. A tablet according to any previous claim, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS, for example, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.

8. A tablet according to any previous claim, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt % and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF,for example, wherein the tablet comprises:(i) at least about 50 wt % and at most about 62 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.

9. A tablet according to any previous claim wherein the tablet comprises:(a) about 53.4 wt % MCC, about 10 wt% PVPcI, about 2.0 wt% SLS, about 6.8 wt% DCP, about 1.5 wt% SSF and wherein the amount of alvelestat or a pharmaceutically acceptable salt thereof is about 26.3 wt% alvelestat tosylate; or(b) about 59.9 wt % MCC, about 10 wt% PVPcI, about 2.0 wt% SLS, about 6.8 wt% DCP, about 1.5 wt% SSF and wherein the amount of alvelestat or a pharmaceutically acceptable salt thereof is about 19.7 wt% alvelestat tosylate.

10. A tablet according to any previous claim wherein the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to about 60 mg, about 80 mg, or about 120 mg of alvelestat free base, for example, wherein the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to (i) about 120 mg or (ii) about 60 mg of alvelestat free base.

11. A tablet according to any previous claim wherein the weight of the tablet is between about 300 mg to about 1200 mg, for example, about 600 mg or about 400 mg.

12. A tablet comprising alvelestat or a pharmaceutically acceptable salt thereof, wherein the amount of alvelestat or pharmaceutically acceptable salt thereof in the tablet corresponds to about 120 mg of alvelestat free base; and wherein the tablet comprises one or more pharmaceutically acceptable excipients.

13. A tablet according to claim 12, wherein the alvelestat or a pharmaceutically acceptable salt thereof is in the form of alvelestat tosylate.

14. A tablet according to claim 12 or claim 13,wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 15 wt% of alvelestat free base and at most about 40 wt% of alvelestat free base, for example, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to at least about 15 wt% of alvelestat free base and at most about 25 wt% of alvelestat free base, for example, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 20 wt% of alvelestat free base.

15. A tablet according to any one of claims 12-14 wherein the tablet comprises:(i) at least one pharmaceutically acceptable excipient that acts as a filler; and / or(ii) at least one pharmaceutically acceptable excipient that acts as a disintegrant; and / or(iii) at least one pharmaceutically acceptable excipient that acts as a surfactant; and / or(iv) at least one pharmaceutically acceptable excipient that acts as a lubricant.

16. A tablet according to any one of claims 12-15 wherein the tablet comprises:(a) microcrystalline cellulose (MCC), for example wherein the tablet comprises at least about 40 wt% MCC and at most about 70 wt% MCC, for example wherein the tablet comprises at least about 50 wt % MCC and at most about 60 wt% MCC; and / or(b) polyvinylpyrrolidone (PVPcI), optionally wherein:(i) the tablet further comprises microcrystalline cellulose (MCC), and wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is from about 1 :3 to about 1 :15, for example wherein the ratio of the amount of PVPcI in the tablet to the amount of MCC in the tablet is from about 1 :4 to about 1 :12; and / or(ii) the tablet comprises at least about 3 wt% PVPcI and at most about 15 wt% PVPcI, for example, wherein the tablet comprises at least about 4.5 wt % PVPcI and at most about 11 wt% PVPcI; and / or(c) sodium lauryl sulfate (SLS), for example, wherein the tablet comprises at least about 0.5 wt% SLS and at most about 2.5 wt% SLS, for example, wherein the tablet comprises at least about 1.1 wt % SLS and at most about 2.2 wt% SLS; and / or(d) Calcium Hydrogen Phosphate Dihydrate (DCP), for example, wherein the tablet comprises at least about 5 wt% DCP and at most about 10 wt% DCP; and / or(e) sodium stearyl fumarate (SSF), for example, wherein the tablet comprises at least about 0.5 wt% SSF and at most about 2 wt% SSF.

17. A tablet according to any one of claims 12-16, wherein the tablet comprises:(i) alvelestat or a pharmaceutically acceptable salt thereof;(ii) MCC;(iii) PVPcI; and(iv) SLS; optionally wherein the tablet further comprises DCP and SSF.

18. A tablet according to any one of claims 12-17, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI; and(iii) at least about 0.5 wt% and at most about 2.5 wt% SLS, for example, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI; and(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS.

19. A tablet according to any one of claims 12-18, wherein the tablet comprises:(i) at least about 40 wt% and at most about 70 wt% MCC;(ii) at least about 3 wt% and at most about 15 wt% PVPcI;(iii) at least about 0.5 wt % and at most about 2.5 wt% SLS;(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF, for example, wherein the tablet comprises:(i) at least about 50 wt % and at most about 60 wt% MCC;(ii) at least about 4.5 wt% and at most about 11 wt% PVPcI;(iii) at least about 1.1 wt % and at most about 2.2 wt% SLS; and(iv) at least about 5 wt% DCP and at most about 10 wt% DCP; and(v) at least about 0.5 wt% SSF and at most about 2 wt% SSF.

20. A tablet according to any one of claims 12-19, wherein the tablet comprises about53.4 wt % MCC, about 10 wt% PVPcI, about 2.0 wt% SLS, about 6.8 wt% DCP, about1.5 wt% SSF and wherein the amount of alvelestat or a pharmaceutically acceptable salt thereof comprises about 26.3 wt% alvelestat tosylate.

21. A tablet according to any one of claims 12-20, wherein the weight of the tablet is between about 500 mg to about 1200 mg, for example, wherein the weight of the tablet is about 600 mg.

22. A tablet according to any previous claim, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 312 mg to about 330 mg MCC, about 54 mg to about 66 mg PVPcI, and about 9 mg to about 15 mg SLS, and optionally, about 36 mg to about 45 mg DCP, and about 6 mg to about 12 mg SSF; preferably wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 120 mg of alvelestat free base, about 320 mg MCC, about 60 mg PVPcI, about 12 mg SLS, about 41 mg DCP, and about 9 mg SSF; most preferably wherein the tablet consists of about 158 mg alvelestat tosylate, about 320 mg MCC, about 60 mg PVPcI, about 12 mg SLS, about 41 mg DCP, about 9 mg SSF, such that the total core weight of the tablet is about 600 mg, and optionally, a coating such as a film coating.

23. A tablet according to any one of claims 1 to 10, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 156 mg to about 165 mg MCC, about 27 mg to about 33 mg PVPcI, and about 4.5 mg to about 7.5 mg SLS, and optionally about about 18 mg to about 23 mg DCP, and about 3 mg to about 6 mg SSF; preferably wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 160 mg MCC, about 30 mg PVPcI, and about 6 mg SLS, about 20 mg DCP, and about 5 mg SSF; most preferably wherein the tablet consists of about 79 mg alvelestat tosylate, about 160 mg MCC, about 30 mg PVPcI, about 6 mg SLS, about 20 mg DCP, and about 5 mg SSF, such that the total core weight of the tablet is about 300 mg, and optionally, a coating such as a film coating.

24. A tablet according to any one of claims 1 to 10, wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 232 mg to about 248 mg MCC, about 36 mg to about 44 mg PVPcI, and about 6 mg to about 10mg SLS, and optionally about 24 mg to about 30 mg DCP, and about 4 mg to about 8 mg SSF; preferably wherein the tablet comprises alvelestat or a pharmaceutically acceptable salt thereof in an amount corresponding to about 60 mg of alvelestat free base, about 240 mg MCC, about 40 mg PVPcI, about 8 mg SLS, about 27 mg DCP, and about 6 mg SSF; most preferably wherein the tablet consists of about 79 mg alvelestat tosylate, about 240 mg MCC, about 40 mg PVPcI, about 8 mg SLS, about 27 mg DCP, and about 6 mg SSF, such that the total core weight of the tablet is about 400 mg, and optionally, a coating such as a film coating.

25. A tablet according to any previous claim wherein the tablet comprises:(i) about 7 wt% MCC extragranularly; and / or(ii) about 3 wt% PVPcI extragranularly; and / or(iii) about 7 wt% MCC, about 3 wt% PVPcI and about 0.5 wt% SSF extragranularly.

26. A tablet according to claim 22, wherein the tablet comprises(i) about 42 mg of MCC extragranularly; and / or(ii) about 18 mg PVPcI extragranularly; and / or(iii) about 42 mg MCC, about 18 mg PVPcI and about 3 mg SSF extragranularly.

27. A tablet according to claim 23, wherein the tablet comprises(i) about 21 mg of MCC extragranularly; and / or(ii) about 9 mg PVPcI extragranularly; and / or(iii) about 21 mg MCC, about 9 mg PVPcI and about 1.5 mg SSF extragranularly.

28. A tablet according to claim 24, wherein the tablet comprises(i) about 28 mg of MCC extragranularly; and / or(ii) about 12 mg PVPcI extragranularly; and / or(iii) about 28 mg MCC, about 12 mg PVPcI and about 2 mg SSF extragranularly.

29. A tablet according to any previous claim wherein the tablet is coated with a film coating.

30. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method of treatment of a disease which is mediated by a-1 antitrypsin deficiency wherein the method comprises administering one or more tablet(s) according to any one of claims 1 to 29 to a subject in need thereof.

31. The alvelestat for use of claim 30, wherein the disease mediated by a-1 antitrypsin deficiency is COPD, emphysema, asthma or bronchiectasis, in particular AATD- mediated emphysema.

32. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method of treating or preventing graft rejection, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of claims 1 to 29 to a subject in need thereof.

33. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method for treating a coronavirus infection and / or preventing progression of a coronavirus disease, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of claims 1 to 29 to a subject in need thereof.

34. Alvelestat or a pharmaceutically acceptable salt thereof for use in a method for treating or preventing bronchiectasis, wherein the method comprises administering an effective amount of alvelestat or a pharmaceutically acceptable salt in the form of one or more tablet(s) according to any one of claims 1 to 29 to a subject in need thereof.

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