Oral delivery of GLP-1 peptide agonists

Abstract

In the present invention it has been found a pharmaceutical formulation comprising a GLP-1 peptide agonist; a C6-C9 fatty acid or a salt thereof or a combination of a C6- C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers can be used to increase the bioavailability of the peptide in the formulation. The salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid each act as permeability enhancers, and improve the bioavailability of the peptide. The pharmaceutical formulation can be used in the treatment of diabetes mellitus and obesity.

Description

[0001] ORAL DELIVERY OF GLP-1 PEPTIDE AGONISTS

[0002] The present disclosure relates to a pharmaceutical formulation comprising a peptide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers. The peptide may be a glucagon-like peptide-1 (GLP-1 ) receptor agonist. The salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6- C9 fatty acid each act as permeability enhancers, and improve the bioavailability of the peptide. The pharmaceutical formulation can be used in the treatment of diabetes mellitus and obesity, for example.

[0003] STATE OF THE ART

[0004] Proteins are most commonly administered parenterally. Oral administration of proteins is very challenging in view of the function of the digestion system, which is to break down peptides before they are able to be absorbed. Proteins and peptides have physiochemical properties which limit their bioavailability, such as high molecular weight, susceptibility to enzymatic hydrolysis and high hydrophilicity.

[0005] Proteins and peptides are able to cross the epithelial cell layer by five possible routes which include passive paracellular diffusion through the hydrophobic tight junctions, by passive or facilitated transcellular diffusion through the lipophilic absorptive cells, by active carrier-mediated transport systems, or by transcytosis. Large peptides and proteins are usually absorbed by passive paracellular diffusion.

[0006] To increase the bioavailability of proteins and peptides, various approaches have been tried including co-administration of protease inhibitors, the use of absorption enhancers to increase permeability across the membrane and modifying a drug to improve resistance to degradation and increase absorption.

[0007] The use of absorption enhancers has been reported in the literature and various classes of absorption enhancers have been used to increase the bioavailability of peptides and proteins. Such absorption enhancers include chelators, such as EDTA and citric acid; synthetic surfactants such as sodium lauryl sulphate, and polyoxyethylene alkyl ethers; and bile salts such as sodium glycocholate and sodium taurocholate.

[0008] Another type of absorption enhancer which has been used are fatty acids and their salts. U.S. patent application US 2023 / 0053812 A1 describes formulations of semaglutide and sodium caprylate in Examples 1 , 2 and 5 and explains that sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), which is a known absorption enhancer, increases water content during storage. US 2023 / 0053812 A1 also explains that the manufacturing process for preparing SNAC is complex. The objective of US 2023 / 0053812 A1 is therefore to find an alternative absorption enhancer to SNAC which could be used to increase the bioavailability of peptides or proteins.

[0009] Patent application WO2016120378 A1 describes pharmaceutical compositions containing a GLP-1 peptide and an absorption enhancer which comprises a salt of a medium-chain fatty acid, having 8-12 carbon atoms. Sodium caprate is specifically referred to and is the absorption enhancer used in Method 1 and Example 1 .

[0010] Patent application WO2016120380 A1 also describes pharmaceutical compositions containing a GLP-1 peptide and an absorption enhancer which comprises a salt of a medium-chain fatty acid, having 8-12 carbon atoms. It mentions that the absorption enhancer can be SNAC or sodium caprate.

[0011] U.S. Patent 9,278,123 discloses a composition comprising semaglutide (a GLP-1 peptide agonist) and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC). The SNAC was used as an absorption enhancer to enhance the bioavailability of semaglutide.

[0012] Semaglutide is a recombinant long acting GLP-1 receptor agonist. The GLP-1 analogue is acylated at lysine 26 with a fatty diacid moiety and has two amino acid substitutions (Ala8 to Aib8 (2-aminoisobutyric acid), Lys34 to Arg34) compared to human GLP-1.

[0013] Semaglutide has been used to improve glycemic control in adults with type 2 diabetes mellitus. It reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated, and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase. Semaglutide has also been used in the treatment of obesity.

[0014] Semaglutide has been authorised in the Ell as Ozempic, for once weekly, subcutaneous use. Novo Nordisk A / S developed a further product, Rybelsus which obtained marketing authorisation in 2020. Rybelsus also contains semaglutide but is for oral use. To improve bioavailability, the absorption enhancer (SNAC) was added.

[0015] Despite the advances in oral formulations of peptides and proteins when administered orally, there still exists a need for formulations that can improve the bioavailability of peptides and proteins so that peptides and proteins can be administered via the preferred oral route rather than via the intravenous route.

[0016] The inventors of the present disclosure have surprisingly found that using a C6-C9 fatty acid or a salt thereof as a permeability enhancer alone or in combination with a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (NAC), substantially increases the bioavailability of a protein or peptide. Furthermore, when sodium N-(8-(2- hydroxybenzoyl)amino)caprylate and sodium caprylate were used as permeability enhancers in a semaglutide formulation, a synergistic increase in the permeability of semaglutide across CaCo-2 cell monolayers was observed.

[0017] Additionally, the use of a C6-C9 fatty acid or a salt thereof alone or in combination with a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (NAC) was found to provide the same bioavailability as SNAC alone. It is possible, therefore, to substitute part of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (NAC) present in a pharmaceutical formulation with a C6-C9 fatty acid or a salt thereof, without affecting the bioavailability of the protein or peptide, i.e., the bioavailability remains the same. This is demonstrated in the Experimental Examples where a formulation comprising semaglutide, SNAC (150 mg) and sodium caprylate (150 mg) was found to have the same permeability as a formulation comprising semaglutide and SNAC (300 mg) (corresponding to the product Rybelsus). Furthermore, when sodium caprylate (300 mg) was used alone, very similar permeability of semaglutide across CaCo-2 cell monolayers was observed, compared to the same amount of SNAC (300 mg) when used alone.

[0018] SUMMARY OF THE INVENTION

[0019] Therefore, a first aspect of the present disclosure is a pharmaceutical formulation comprising: a peptide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers.

[0020] The peptide may be a GLP-1 peptide agonist. Such GLP-1 peptide agonists include semaglutide, liraglutide, exenatide, exendin-4, tirzepatide, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, and pharmaceutically acceptable salts thereof. Preferably, the peptide is semaglutide.

[0021] In one embodiment of the first aspect of the present disclosure, the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid (NAC) is the sodium, potassium or ammonium salt, preferably the sodium salt (SNAC).

[0022] In another embodiment of the first aspect of the present disclosure, the C6-C9 fatty acid or a salt thereof is caproic acid, caprylic acid, enthanoic acid or pelargonic acid, preferably, caprylic acid and more preferably sodium caprylate.

[0023] In one embodiment of the first aspect of the present disclosure, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5.

[0024] In one embodiment of the first aspect of the present disclosure, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5.

[0025] In one embodiment of the first aspect of the present disclosure, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2. In one embodiment of the first aspect of the present disclosure, the C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N- (8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg.

[0026] In an embodiment of the first aspect of the present disclosure, the pharmaceutical formulation comprises semaglutide; sodium N-(8-(2-hydroxybenzoyl)amino)caprylate; and sodium caprylate.

[0027] In an embodiment of the first aspect of the present disclosure, the pharmaceutical formulation comprises semaglutide; and sodium caprylate.

[0028] In an embodiment of the first aspect of the present disclosure, the pharmaceutical formulation comprises semaglutide; and sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers, preferably present in a weight of 200 to 800 mg; wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0029] A second aspect of the present disclosure is a method of preparing a pharmaceutical formulation comprising the steps of: a) sieving a peptide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients from step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets.

[0030] In a preferred aspect of the present disclosure is a method of preparing a pharmaceutical formulation comprising the steps of: a) sieving a peptide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; b) granulating the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients by dry granulation; c) pressing the granules from step b) into tablets; and d) optionally coating the tablets.

[0031] In a further preferred aspect of the present disclosure is a method of preparing a pharmaceutical formulation comprising the steps of: a) sieving a peptide; b) mixing the sieved peptide with a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; c) granulating the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients by dry granulation; d) adding a lubricant to the granulated mixture of step c); e) pressing the granules from step d) into tablets; and f) optionally coating the tablets.

[0032] In another preferred aspect of the present disclosure is a method of preparing a pharmaceutical formulation comprising the steps of: a) mixing together a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and a lubricant; and optionally one or more additional excipients; b) granulating the mixture of step a) by dry granulation; c) mixing the granulated mixture of step b) with a peptide and optionally one or more additional excipients; d) adding a lubricant to the mixture of step c); e) pressing the granules from step d) into tablets; and f) optionally coating the tablets.

[0033] A third aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers, for use in the treatment of diabetes or obesity.

[0034] One embodiment of the third aspect of the present disclosure, is a pharmaceutical formulation comprising: semaglutide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers, for use in the treatment of diabetes or obesity.

[0035] Another embodiment of the third aspect of the present disclosure, is a pharmaceutical formulation comprising: semaglutide; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, for use in the treatment of diabetes or obesity, optionally wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0036] Another embodiment of the third aspect of the present disclosure, is a pharmaceutical formulation comprising: semaglutide; sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, for use in the treatment of diabetes or obesity, optionally wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0037] BRIEF DESCRIPTION OF THE FIGURES

[0038] Figure 1 : Semaglutide permeability across CaCo-2 cell monolayers, in the presence of SNAC, or in the presence of SNAC and sodium caprylate (C8) at different ratios. Cumulative transport (pg / mL) is shown with respect to time (minutes).

[0039] Figure 2: Semaglutide permeability across CaCo-2 cell monolayers, in the presence of SNAC and sodium caprylate (C8) or in the presence of SNAC and sodium caprate (C10), at different ratios. Cumulative transport (pg / mL) is shown with respect to time (minutes).

[0040] *Blend 9 containing semaglutide, SNAC and sodium caprate (C10) did not form a homogenous solution and precipitation was observed.

[0041] Figure 3: Semaglutide permeability across CaCo-2 cell monolayers, in binary mixtures with SNAC and in ternary mixtures with sodium caprylate (C8). Cumulative transport (pg / mL) is shown with respect to time (minutes).

[0042] Figure 4: Semaglutide permeability across CaCo-2 cell monolayers, in binary mixtures with SNAC or sodium caprylate (C8). Cumulative transport (pg / mL) is shown with respect to time (minutes).

[0043] Figure 5: Semaglutide permeability across CaCo-2 cell monolayers, in binary mixtures with SNAC or sodium caprylate (C8). Cumulative transport (pg / mL) is shown with respect to time (minutes).

[0044] Figure 6: Semaglutide permeability across CaCo-2 cell monolayers, in the presence of SNAC and sodium caprylate (C8) or in the presence of sodium caprylate (C8), at different ratios and using different amounts of semaglutide. Cumulative transport (pg / mL) is shown with respect to time (minutes).

[0045] Figure 7: Semaglutide permeability across CaCo-2 cell monolayers, in the presence of SNAC and sodium caprylate (C8) or in the presence of SNAC and sodium caprate (C10), at different ratios. Cumulative transport (pg / mL) is shown with respect to time (minutes).

[0046] *Blends 9 and 1 Containing semaglutide, SNAC and sodium caprate (C10) did not form a homogenous solution and precipitation was observed.

[0047] Figure 8a shows the plasma concentration (ng / mL) of semaglutide in the patients’ blood plasma after a single dose administration of the test tablet or the reference tablet up to 504 hours after administration.

[0048] Figure 8b shows a section of the graph in Figure 8a up to 72 hours.

[0049] DESCRIPTION OF THE INVENTION

[0050] The inventors of the present invention have surprisingly found that a pharmaceutical formulation comprising: a peptide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers, is able to substantially increase the bioavailability of the peptide or provide the same bioavailability as a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid alone. Additionally, the formulation can be administered orally in a suitable dosage form, such as a tablet.

[0051] Figure 1 shows that far greater permeability of a peptide (such as semaglutide) was observed when a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (such as SNAC) was used in combination with a C6-C9 fatty acid or a salt thereof (such as sodium caprylate), rather than a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid alone. Thus, the pharmaceutical formulation of the present invention is able to substantially increase the bioavailability of a peptide. Furthermore, the inventors of the present invention also surprisingly found that it is possible to substitute the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid (NAC) present in a pharmaceutical formulation either completely or partially with a C6-C9 fatty acid or a salt thereof, without affecting the bioavailability of the peptide.

[0052] Furthermore, as shown in Figure 2, the inventors of the present invention observed greater permeability of a peptide (such as semaglutide) when a salt of a C8 fatty acid (sodium caprylate) was formulated with a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid (such as SNAC) compared to a salt of a C10 fatty acid (sodium caprate) formulated with a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (such as SNAC).

[0053] Figure 3 shows that formulating a peptide (such as semaglutide) with a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid (such as SNAC) in an amount of 150 mg, resulted in zero permeability of the peptide. Furthermore, formulating a peptide (such as semaglutide) in an amount of 14 mg with a salt of a C8 fatty acid (such as sodium caprylate) in an amount of 150 mg, also resulted in zero permeability of the peptide. However, when formulating a peptide (such as semaglutide) with both a salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid (such as SNAC) and a salt of a C8 fatty acid (such as sodium caprylate), a synergistic effect in the permeability of the peptide was observed. Figure 3 also shows that it is possible to substitute the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid (such as SNAC) in a pharmaceutical formulation either completely or partially with a salt of a C8 fatty acid (such as sodium caprylate), without reducing the permeability of the peptide.

[0054] Figure 4 shows that as the amount of either a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid (such as SNAC) or a salt of a C8 fatty acid (such as sodium caprylate) is increased in the formulation, the permeability of the peptide (such as semaglutide) increases. Furthermore, a formulation containing a peptide and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid (such as SNAC) was found to have a similar permeability as a formulation containing a peptide and a salt of a C8 fatty acid (such as sodium caprylate). As used herein, the term “peptide” refers to a biopolymer comprising chains of amino acid monomers linked by peptide bonds, having a molecular mass of less than 10,000 Da. The peptide may be a linear peptide or a cyclic peptide.

[0055] As used herein, the term “GLP-1 peptide agonist” refers to a compound, which is capable of binding to the GLP-1 receptor and fully or partially activates it. The term is synonymous with the terms “GLP-1 agonist”, "GLP-1 peptide", "GLP-1 receptor agonist", "GLP-1 agonist" and "GLP-1 receptor agonist peptide".

[0056] The term "GLP-1 ", "GLP-1 peptide" or "hGLP-1 " refers to the human Glucagon-Like Peptide-1 (GLP-1 (7-37)).

[0057] The Homo sapiens GLP-1 (7-37) sequence is:

[0058] HAEGTFTSDV SSYLEGQAAK EFIAWLVKGR G (SEQ ID 1 ); and the Homo sapiens GLP-1 (7-35) sequence is:

[0059] HAEGTFTSDV SSYLEGQAAK EFIAWLVKG (SEQ ID 2).

[0060] In the sequence listings, the first amino acid residue (i.e. histidine) of SEQ ID 1 and SEQ ID 2 is assigned No. 1. However, according to established practice in the art, this histidine residue is referred to as No. 7, and subsequent amino acid residues are numbered accordingly, ending with glycine No. 37. Therefore, generally, any reference herein to an amino acid residue number or a position number of the GLP-1 (7-37) sequence is to the sequence starting with His at position 7 and ending with Gly at position 37.

[0061] The term "GLP-1 analogue" or "analogue of GLP-1 " refers to a peptide, or a compound, which is a variant of GLP-1 (7-37) (SEQ ID 1 ) or of GLP-1 (7-35) (SEQ ID 2), in which one or more substituents have been covalently attached to the peptide.

[0062] As used herein, the term “insulin analog” refers to any of several types of medical insulin that are altered forms of the hormone insulin, different from any occurring in nature, but still available to the human body for performing the same action as human insulin in terms of controlling blood glucose levels in diabetes.

[0063] As used herein, the term “permeability enhancer” refers to an agent whose function is to increase absorption by enhancing membrane permeability. The term “permeation enhancer” is synonymous with the term “permeability enhancer”.

[0064] As used herein, the term “C6-C9 fatty acid”, refers to a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated, wherein the carboxylic acid contains a total of 6, 7, 8 or 9 carbon atoms.

[0065] As used herein, “sodium N-(8-(2-hydroxybenzoyl)amino)caprylate” may also be referred to as “sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid”, the “sodium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid”, the “sodium salt of N-(8-(2- hydroxybenzoyl)amino)caprylate”, “SNAC” and “salcaprozate sodium”.

[0066] As used herein “as the sole permeability enhancers” means that only the specified permeability enhancers are included in pharmaceutical formulation. For example, where the permeability enhancers are a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid, and it is specified that these are the “sole permeability enhancers”, no other permeability enhancers are present in the formulation.

[0067] Peptide

[0068] A first aspect of the present disclosure is a pharmaceutical formulation comprising: a peptide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers.

[0069] The peptide in the pharmaceutical formulation may be selected from: a) insulin, insulin aspart, insulin glulisine, insulin glargine, insulin detemir, NPH insulin and insulin degludec; b) an insulin analog such as insulin lispro, insulin PEGIispro; c) GLP-1 or a GLP-1 analog such as an acylated GLP-1 analog or a diacylated GLP-1 analog); d) GLP-1 peptide agonist such as, semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; e) a GLP-2 agonist or analog (e.g., teduglutide or elsiglutide), amylin, an amylin analog, pramlintide, a somatostatin analog (e.g., octreotide, lanreotide, or pasireotide), desmopressin (e.g., desmopressin acetate), calcitonin (e.g., calcitonin-salmon), parathyroid hormone (PTH) and parathyroid hormone- related protein (PTHrP); or f) a dual GLP-1 and GIP (gastric inhibitory polypeptide) receptor agonist such as tirzepatide.

[0070] In one embodiment, the pharmaceutical formulation provided herein comprises a GLP- 1 peptide agonist.

[0071] The GLP-1 peptide agonist may be selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof.

[0072] In a preferred embodiment, the GLP-1 peptide agonist is selected from semaglutide, liraglutide and tirzepatide. Preferably, the GLP-1 peptide agonist is semaglutide.

[0073] Salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid

[0074] The pharmaceutical formulation of the present disclosure may contain a salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid.

[0075] The salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid may be selected from the group consisting of the sodium, potassium and ammonium salt.

[0076] Thus, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid may be selected from sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid.

[0077] In a preferred embodiment, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC).

[0078] C6-C9 fatty acid or a salt thereof

[0079] The C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation includes C6- C9 fatty acids or a salt thereof, wherein the aliphatic chain in the C6-C9 fatty acid is saturated or unsaturated.

[0080] The aliphatic chain in the C6-C9 fatty acid or a salt thereof, may be unsaturated and contain one, two or three unsaturations (double bonds) along the length of the chain. In one embodiment, the aliphatic chain contains a single double bond.

[0081] The C6-C9 fatty acid or a salt thereof, having an unsaturated aliphatic chain may be selected from hex-5-enoic acid, hex-4-enoic acid, hex-3-enoic acid and hex-2-enoic acid.

[0082] The C6-C9 fatty acid or a salt thereof, having an unsaturated aliphatic chain may be selected from hep-6-enoic acid, hep-5-enoic acid, hep-4-enoic acid, hep-3-enoic acid and hep-2-enoic acid.

[0083] The C6-C9 fatty acid or a salt thereof, having an unsaturated aliphatic chain may be selected from oct-7-enoic acid, oct-6-enoicacid, oct-5-enoicacid, oct-4-enoic acid, oct- 3-enoic acid, and oct-2 -enoic acid.

[0084] The C6-C9 fatty acid or a salt thereof, having an unsaturated aliphatic chain may be selected from non-8-enoic acid, non-7-enoic acid, non-6-enoic acid, non-5-enoic acid, non-4-enoic acid, non-3-enoic acid, and non-2-enoic acid.

[0085] In one embodiment, the C6-C9 fatty acid or a salt thereof, has a saturated aliphatic chain. Thus, in one embodiment, the C6-C9 fatty acid is selected from the group consisting of caproic acid, enthanoic acid, caprylic acid, and pelargonic acid. The IIIPAC name of these acids are hexanoic acid, heptanoic acid, octanoic acid and nonanoic acid, respectively.

[0086] In one embodiment the pharmaceutical formulation comprises a salt of the C6-C9 fatty acid. The salt of the C6-C9 fatty acid may be the sodium, potassium or ammonium salt. Preferably the salt of the C6-C9 fatty acid is the sodium salt.

[0087] In one embodiment, the salt of the C6-C9 fatty acid is selected from the group consisting of sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, and ammonium nonanoate.

[0088] Preferably, the salt of the C6-C9 fatty acid is selected from the group consisting of sodium caprylate, potassium caprylate and ammonium caprylate. More preferably, the salt of the C6-C9 fatty acid is sodium caprylate.

[0089] Preferably the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in the pharmaceutical formulation. Other known permeability enhancers such as L-Arginine and / or sodium caprate are excluded from the pharmaceutical formulation.

[0090] Formulations

[0091] A first aspect of the present disclosure is a pharmaceutical formulation comprising: a peptide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid.

[0092] In one embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a peptide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers. In one embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a peptide; and a C6-C9 fatty acid or a salt thereof as the sole permeability enhancer.

[0093] In one embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a peptide; and a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers.

[0094] The peptide may be a GLP-1 peptide agonist. The GLP-1 peptide agonist may be selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof.

[0095] In a preferred embodiment, the GLP-1 peptide agonist is selected from semaglutide, liraglutide and tirzepatide. Preferably, the GLP-1 peptide agonist is semaglutide.

[0096] The salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid may be selected from the group consisting of the sodium, potassium and ammonium salt. Thus, the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid may be selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid.

[0097] In a preferred embodiment, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC).

[0098] The C6-C9 fatty acid or a salt thereof, having an unsaturated aliphatic chain may be selected from hex-5-enoic acid, hex-4-enoic acid, hex-3-enoic acid and hex-2-enoic acid.

[0099] The C6-C9 fatty acid or a salt thereof, having an unsaturated aliphatic chain may be selected from hep-6-enoic acid, hep-5-enoic acid, hep-4-enoic acid, hep-3-enoic acid and hep-2-enoic acid. The C6-C9 fatty acid or a salt thereof, having an unsaturated aliphatic chain may be selected from oct-7-enoic acid, oct-6-enoic acid, oct-5-enoic acid, oct-4-enoic acid, oct- 3-enoic acid, and oct-2 -enoic acid.

[0100] The C6-C9 fatty acid or a salt thereof, having an unsaturated aliphatic chain may be selected from non-8-enoic acid, non-7-enoic acid, non-6-enoic acid, non-5-enoic acid, non-4-enoic acid, non-3-enoic acid, and non-2-enoic acid.

[0101] In one embodiment, the C6-C9 fatty acid or a salt thereof, has a saturated aliphatic chain. Thus, in one embodiment, the C6-C9 fatty acid is selected from the group consisting of caproic acid, enthanoic acid, caprylic acid, and pelargonic acid. The IIIPAC name of these acids are hexanoic acid, heptanoic acid, octanoic acid and nonanoic acid, respectively.

[0102] In one embodiment the pharmaceutical formulation comprises a salt of the C6-C9 fatty acid. The salt of the C6-C9 fatty acid may be the sodium, potassium or ammonium salt. Preferably the salt of the C6-C9 fatty acid is the sodium salt.

[0103] In one embodiment, the salt of the C6-C9 fatty acid is selected from the group consisting of sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, and ammonium nonanoate.

[0104] Preferably, the salt of the C6-C9 fatty acid is selected from the group consisting of sodium caprylate, potassium caprylate and ammonium caprylate. More preferably, the salt of the C6-C9 fatty acid is sodium caprylate.

[0105] One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers.

[0106] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers.

[0107] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, tirzepatide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers.

[0108] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers.

[0109] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers.

[0110] One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium , potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers.

[0111] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium or potassium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers.

[0112] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, tirzepatide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers.

[0113] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers.

[0114] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate as the sole permeability enhancers.

[0115] One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium , potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein the C6-C9 fatty acid or a salt thereof is selected from the group consisting of caproic acid, caprylic acid, enthanoic acid and pelargonic acid.

[0116] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium or potassium salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein the C6-C9 fatty acid or a salt thereof is selected from the group consisting of caproic acid, caprylic acid, enthanoic acid and pelargonic acid.

[0117] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers.

[0118] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; and caprylic acid or a salt thereof or a combination of caprylic acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers.

[0119] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; and caprylic acid or a salt thereof or a combination of caprylic acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate.

[0120] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; sodium caprylate or a combination sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers.

[0121] In one embodiment of the pharmaceutical formulation, the weight ratio of the salt of N- (8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0122] In one embodiment of the pharmaceutical formulation, the weight ratio of sodium N-(8- (2-hydroxybenzoyl)amino)caprylate and caprylic acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0123] In one embodiment of the pharmaceutical formulation, the weight ratio of sodium N-(8- (2-hydroxybenzoyl)amino)caprylate and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 : 1 to 1 :2.

[0124] In one embodiment of the pharmaceutical formulation, the weight ratio of sodium N-(8- (2-hydroxybenzoyl)amino)caprylate and sodium caprylate is 1 :1 to 1 :3.

[0125] In one embodiment of the pharmaceutical formulation, the weight ratio of sodium N-(8- (2-hydroxybenzoyl)amino)caprylate and sodium caprylate is 1 :1 to 1 :2.

[0126] In one embodiment of the pharmaceutical formulation, the weight ratio of sodium N-(8- (2-hydroxybenzoyl)amino)caprylate and sodium caprylate is 1 :1 or 1 :2.

[0127] In one embodiment of the pharmaceutical formulation, the weight of the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg.

[0128] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg.

[0129] In one embodiment of the pharmaceutical formulation, the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0130] In one embodiment of the pharmaceutical formulation, the weight of caprylic acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0131] In one embodiment of the pharmaceutical formulation, the weight of the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0132] In one embodiment of the pharmaceutical formulation, the weight of the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg.

[0133] In one embodiment of the pharmaceutical formulation, the weight of the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 50 to 400 mg, and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg.

[0134] In one embodiment of the pharmaceutical formulation, the weight of the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 50 to 400 mg, and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 600 mg.

[0135] In one embodiment of the pharmaceutical formulation, the weight of the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 100 to 350 mg, and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 600 mg.

[0136] In one embodiment of the pharmaceutical formulation, the weight of the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 100 to 200 mg and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 100 to 350 mg. In one embodiment of the pharmaceutical formulation, the weight of the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 100 to 200 mg and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 150 to 350 mg.

[0137] In one embodiment of the pharmaceutical formulation, the weight of the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 150 mg and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 150 mg or 300 mg.

[0138] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg .preferably 100 to 200 mg, preferably 150 mg and the weight of caprylic acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0139] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, and the weight of caprylic acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg.

[0140] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 50 to 400 mg, and the weight of caprylic acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg.

[0141] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 50 to 400 mg, and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 600 mg.

[0142] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 100 to 350 mg, and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 600 mg.

[0143] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 100 to 200 mg and the weight of caprylic acid or a salt thereof in the pharmaceutical formulation is 100 to 350 mg.

[0144] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 150 mg and the weight of caprylic acid or a salt thereof in the pharmaceutical formulation is 150 mg or 300 mg.

[0145] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg and the weight of sodium caprylate in the pharmaceutical formulation is 50 to 500 mg, preferably 100 to 350 mg, preferably 150 mg or 300 mg.

[0146] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, and the weight of sodium caprylate in the pharmaceutical formulation is 50 to 800 mg.

[0147] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 50 to 400 mg, and the weight of sodium caprylate in the pharmaceutical formulation is 50 to 800 mg.

[0148] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 50 to 400 mg, and the weight of sodium caprylate in the pharmaceutical formulation is 50 to 600 mg.

[0149] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 100 to 350 mg, and the weight of sodium caprylate in the pharmaceutical formulation is 50 to 600 mg.

[0150] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 100 to 200 mg and the weight of sodium caprylate in the pharmaceutical formulation is 100 to 350 mg.

[0151] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 100 to 200 mg and the weight of sodium caprylate in the pharmaceutical formulation is 150 to 300 mg.

[0152] In one embodiment of the pharmaceutical formulation, the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 150 mg and the weight of sodium caprylate in the pharmaceutical formulation is 150 mg or 300 mg.

[0153] In one embodiment of the pharmaceutical formulation the permeability enhancers are present in the pharmaceutical formulation in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg.

[0154] In one embodiment of the pharmaceutical formulation the C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg.

[0155] In one embodiment of the pharmaceutical formulation the C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg.

[0156] In one embodiment of the pharmaceutical formulation the C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 250 to 750 mg.

[0157] In one embodiment of the pharmaceutical formulation the C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 to 600 mg.

[0158] In one embodiment of the pharmaceutical formulation the C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 mg.

[0159] In one embodiment of the pharmaceutical formulation the C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 450 mg.

[0160] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg.

[0161] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg.

[0162] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 250 to 750 mg.

[0163] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 to 600 mg. In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 mg.

[0164] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 450 mg.

[0165] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers are present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg.

[0166] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers are present in a weight of 200 to 800 mg.

[0167] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers are present in a weight of 250 to 750 mg.

[0168] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers are present in a weight of 300 to 600 mg.

[0169] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers are present in a weight of 300 mg.

[0170] In one embodiment of the pharmaceutical formulation sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers are present in a weight of 450 mg. One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0171] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0172] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2. Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0173] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0174] One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium, potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when the sodium, potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the sodium, potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0175] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium or potassium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when the sodium or potassium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the sodium or potassium salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0176] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0177] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when sodium N- (8-(2-hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0178] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when sodium N-(8-(2- hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0179] One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium , potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg; wherein the C6-C9 fatty acid or a salt thereof, is selected from the group consisting of caproic acid, caprylic acid, enthanoic acid and pelargonic acid, and wherein when the sodium, potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the sodium, potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0180] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium or potassium salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg; wherein the C6-C9 fatty acid or a salt thereof is selected from the group consisting of caproic acid, caprylic acid, enthanoic acid and pelargonic acid, and wherein when the sodium or potassium salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the sodium or potassium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0181] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when sodium N- (8-(2-hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0182] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; and caprylic acid or a salt thereof or a combination of caprylic acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when sodium N-(8-(2- hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate and caprylic acid or a salt thereof is 3:1 to 1 :5, preferably 2: 1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0183] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; caprylic acid or a salt thereof or a combination of caprylic acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate and caprylic acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2. Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; and sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0184] One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0185] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0186] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, tirzepatide and pharmaceutically acceptable salts thereof; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; wherein when the salt of N- (8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0187] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; wherein when the salt of N- (8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0188] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0189] One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a sodium, potassium or ammonium salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; wherein when the sodium, potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the sodium, potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0190] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; and sodium caprylate or a combination of sodium caprylate and a sodium or potassium salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; wherein when the sodium or potassium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the sodium or potassium salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0191] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, tirzepatide and pharmaceutically acceptable salts thereof; and sodium caprylate or a combination of sodium caprylate and sodium N-(8- (2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; wherein when sodium N- (8-(2-hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0192] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; and sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; wherein when sodium N- (8-(2-hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0193] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; and sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate and sodium caprylate is 3: 1 to 1 :5, preferably 2:1 to 1 :4, further preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0194] One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein the weight of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0195] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0196] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, tirzepatide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0197] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0198] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg; wherein the weight of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0199] One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium , potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein the weight of the sodium, potassium or ammonium salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0200] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium or potassium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein the weight of the sodium or potassium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0201] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, tirzepatide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0202] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0203] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg, wherein the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0204] One embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium , potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg; wherein the C6-C9 fatty acid or a salt thereof is selected from the group consisting of caproic acid, caprylic acid, enthanoic acid and pelargonic acid, and wherein the weight of the sodium, potassium or ammonium salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0205] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a sodium or potassium salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers preferably present in a weight of 200 to 800 mg; wherein the C6-C9 fatty acid or a salt thereof selected from the group consisting of caproic acid, caprylic acid, enthanoic acid and pelargonic acid; and wherein the weight of the sodium or potassium salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0206] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and pharmaceutically acceptable salts thereof; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg; wherein the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0207] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide and pharmaceutically acceptable salts thereof; and caprylic acid or a salt thereof or a combination of caprylic acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg; wherein the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of caprylic acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0208] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; and caprylic acid or a salt thereof or a combination of caprylic acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg; wherein the weight of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of caprylic acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0209] Another embodiment of the first aspect of the present disclosure is a pharmaceutical formulation comprising: semaglutide; and sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers preferably present in a weight of 200 to 800 mg; wherein the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of sodium caprylate in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0210] In another embodiment of the first aspect of the present disclosure the weight of the peptide, preferably semaglutide, in the pharmaceutical composition is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, further preferably 1 to 30 mg, further preferably 1 to 25 mg, such as 25 mg, further preferably 1 to 20 mg, more preferably 1 to 14 mg, such as 1 .5, 3, 4, 7, 9 or 14 mg, further preferably 3 to 14 mg.

[0211] Additives

[0212] The pharmaceutical formulation of the present disclosure may contain one or more excipients selected from diluent, disintegrant, binder, lubricant, basifier, water soluble agent and anti-oxidant or combinations thereof.

[0213] The pharmaceutical formulation of the present disclosure may contain one or more diluents. Certain non-limiting examples of diluents include polyvinylpyrrolidone, microcrystalline cellulose, maltodextrin, sucrose, xylitol, lactose, dextrose, sorbitol, dextrates, lactitol, kaolin, mannitol, starlac, starch, modified starches, dibasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium sulfate, magnesium carbonate, magnesium oxide.

[0214] In one embodiment, the diluent is selected from polyvinylpyrrolidone, silicified microcrystalline cellulose, maltodextrin, sucrose, Xylitol, microcrystalline cellulose, lactose monohydrate and combinations thereof.

[0215] Preferably the pharmaceutical formulation of the present disclosure comprises microcrystalline cellulose.

[0216] The pharmaceutical formulation of the present disclosure may contain one or more binders. Certain non-limiting examples of binders include cellulose and its derivatives including, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose and hydroxyethyl cellulose, carboxymethyl cellulose; gelatin, liquid glucose; starch and its derivatives; hydrocolloids; sugars; polyvinylpyrrolidone, sodium alginate, acacia, alginic acid, tragacanth; and combinations thereof.

[0217] Preferably the pharmaceutical formulation of the present disclosure comprises polyvinylpyrrolidone.

[0218] The pharmaceutical formulation of the present disclosure may contain one or more disintegrants. Certain non-limiting examples of disintegrants include cellulose and its derivatives including low-substituted hydroxypropyl cellulose; cross-linked polyvinylpyrrolidone; polyvinylpyrrolidone; cross-linked sodium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose; sodium starch glycolate; ion-exchange resins; starch and modified starches; formalincasein; used either alone or combinations thereof. The pharmaceutical formulation of the present disclosure may contain one or more lubricants and / or glidants. Certain non-limiting examples of lubricants include calcium stearate, magnesium stearate, glycerol behenate, mineral oil, polyethylene glycol, sodium stearyl fumarate, stearic acid, talc, vegetable oil, and zinc stearate, used either alone or combinations thereof. Certain non-limiting examples of glidants include talc, silicon dioxide, cornstarch and the like used either alone or in combination thereof.

[0219] Preferably the pharmaceutical formulation of the present disclosure comprises magnesium stearate.

[0220] The pharmaceutical formulation of the present disclosure may contain one or more basifiers. A basifier is a compound which provides an alkaline environment on dissolution of the active ingredient. Certain non-limiting examples of basifiers include calcium carbonate, sodium carbonate, sodium bicarbonate, magnesium hydroxide and aluminium hydroxide.

[0221] In one embodiment of the first aspect of the present disclosure, the pharmaceutical formulation additionally comprises one or more excipients.

[0222] In one embodiment of the first aspect of the present disclosure, the pharmaceutical formulation additionally comprises one or more excipients selected from diluents, binders, lubricants and basifiers.

[0223] In one embodiment of the first aspect of the present disclosure, the pharmaceutical formulation additionally comprises one or more excipients selected from the group consisting of silicified microcrystalline cellulose, maltodextrin, sucrose, Xylitol, microcrystalline cellulose, lactose monohydrate, polyvinylpyrrolidone, and magnesium stearate.

[0224] In one embodiment of the first aspect of the present disclosure, the pharmaceutical formulation additionally comprises one or more excipients selected from the group consisting of microcrystalline cellulose, polyvinylpyrrolidone, and magnesium stearate.

[0225] In one embodiment of the first aspect of the present disclosure, the pharmaceutical formulation additionally comprises microcrystalline cellulose, polyvinylpyrrolidone, and magnesium stearate.

[0226] Dosage Forms

[0227] In one embodiment of the first aspect of the present disclosure, the pharmaceutical formulation is for oral administration. Thus, the formulation is an oral pharmaceutical formulation.

[0228] The pharmaceutical formulation of the present disclosure may be administered in the form of a tablet, pastille, capsule, gel, powder, solution, suspension, syrup or granules.

[0229] Preferably, the pharmaceutical formulation is a solid oral formulation. The pharmaceutical formulation of the present disclosure may be a solid oral formulation in the form of a tablet, pastille or capsule, most preferably in the form of a tablet. The tablet may be film-coated.

[0230] The tablet may be comprised of one or more layers. In one embodiment, the tablet may have one, two, three or four layers. For example, the tablet may be a monolayer tablet, a bi layer tablet or a tri layer tablet.

[0231] In one embodiment the tablet may be a monolithic tablet. In monolithic tablets, the peptide is equally distributed throughout the tablet.

[0232] Tablet coating

[0233] The pharmaceutical formulation of the present disclosure may be in the form of a tablet. The tablet may have a core and at least one coating. The coating may be a continuous layer surrounding the tablet core.

[0234] Coatings may be prepared according to methods known in the art. For example, the coating may be an immediate release coating, which refers to a coating that dissolves independently of the pH of the surroundings.

[0235] The coating may dissolve at a certain pH. For example, the coating may not dissolve in gastric fluid in humans. The coating may therefore dissolve at a pH of 6.0 or higher, such as at pH 6.5 or higher, pH 7.0 or higher, or pH 7.2 or higher. The coating may be resistant to dissolution at a pH below pH 5.5, such as below pH 6.0, below pH 6.5, or below pH 7.0.

[0236] In some embodiments the coating may comprise an anionic copolymer. For example, the coating may comprise a copolymer derived from the monomers a) methyl methacrylate, b) methyl acrylate, and c) methacrylic acid.

[0237] The coating may comprise a polymer selected from the group comprising ethyl cellulose, polyvinyl alcohol, hydroxypropylmethylcellulose (HPMC), Opadry Clear, Opadry II Yellow, Opadry White, Pharmacoat and Kollicoat.

[0238] As used herein the term "Opadry Clear" refers to a composition prepared using Opadry® Clear 03K19229 (as sold by Colorcon, PA, USA, in 2014). "Opadry II Yellow" refers to a composition comprising polyvinyl alcohol and may be obtained from Colorcon, PA, USA, in the form of the product sold as product code 85F32410 in 2014. “Opadry White" refers to a composition prepared using Opadry® White obtained from Colorcon, PA, USA, in the form of the product sold as product code 03F180011 in 2014. “Pharmacoat” may be obtained from Shin-Etsu, Tokyo, Japan, in the form of the product sold as Pharmacoat® 603 in 2014. “Kollicoat” may be obtained from BASF, Ludwigshafen, Germany, in the form of the product sold as Kollicoat® IR in 2014.

[0239] Preparation of formulation

[0240] A second aspect of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a peptide; and a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid; b) mixing together the peptide; and the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets.

[0241] Wherein step c) may comprise the steps of: (i) compacting the mixed powder from step b), (ii) sieving the compacted powder, (iii) optionally adding extragranular excipients, and (iv) optionally coating.

[0242] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a peptide; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid; and optionally one or more excipients; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets.

[0243] Wherein step c) may comprise the steps of: (i) compacting the mixed powder from step b), (ii) sieving the compacted powder, (iii) optionally adding extragranular excipients, and (iv) optionally coating.

[0244] The peptide may be any peptide as described herein. In one embodiment, peptide is a GLP-1 peptide agonist.

[0245] The GLP-1 peptide agonist may be selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof. In a preferred embodiment, the GLP-1 peptide agonist is selected from semaglutide, liraglutide and tirzepatide. Preferably, the GLP-1 peptide agonist is semaglutide.

[0246] The salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid may be selected from the group consisting of the sodium, potassium and ammonium salt.

[0247] Thus, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid may be selected from sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid.

[0248] In a preferred embodiment, the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid (SNAC).

[0249] The salt of the C6-C9 fatty acid may be as described herein. Thus, the salt of the C6- C9 fatty acid may be the sodium, potassium or ammonium salt. Preferably the salt of the C6-C9 fatty acid is the sodium salt.

[0250] In one embodiment, the salt of the C6-C9 fatty acid is selected from the group consisting of sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, and ammonium nonanoate.

[0251] Preferably, the salt of the C6-C9 fatty acid is selected from the group consisting of sodium caprylate, potassium caprylate and ammonium caprylate. More preferably, the salt of the C6-C9 fatty acid is sodium caprylate.

[0252] In one embodiment of the method for preparing a pharmaceutical formulation as described herein, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2. Thus, one embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 : 1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0253] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0254] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid, the C6-C9 fatty acid or a salt thereof, and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1:4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0255] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the sodium N- (8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0256] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and optionally one or more excipients; b) mixing together the peptide; the sodium caprylate or the combination of the sodium caprylate and the sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) and sodium caprylate in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0257] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving semaglutide; sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients; b) mixing together the semaglutide; sodium caprylate or the combination of sodium caprylate and the sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC); and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) and sodium caprylate in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0258] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a peptide; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; b) pressing the granules from step a) into tablets, preferably using direct compression; and c) optionally coating the tablets; wherein when a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 : 1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0259] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; b) granulating a peptide with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein when a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 : 1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0260] In one embodiment, dry granulation is carried out using roller compaction.

[0261] In one embodiment of the pharmaceutical formulation the permeability enhancers are present in the pharmaceutical formulation in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg.

[0262] Thus, one embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0263] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0264] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid, the C6-C9 fatty acid or a salt thereof, and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0265] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the sodium N- (8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0266] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and optionally one or more excipients; b) mixing together the peptide; the sodium caprylate or the combination of the sodium caprylate and the sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) and sodium caprylate in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0267] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving semaglutide; sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; and optionally one or more excipients; b) mixing together the semaglutide; sodium caprylate or the combination of sodium caprylate and the sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC); and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein when sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) is present in the pharmaceutical formulation, the weight ratio of sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) and sodium caprylate in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0268] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a peptide; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; and optionally one or more excipients by dry granulation; b) pressing the granules from step a) into tablets, preferably using direct compression; and c) optionally coating the tablets; wherein when a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 : 1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0269] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; and optionally one or more excipients by dry granulation; b) granulating a peptide with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein when a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is preferably 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 : 1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0270] Thus, one embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0271] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 00 to 400 mg, preferably 50 to 400, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0272] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0273] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the sodium N- (8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0274] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients; b) mixing together the peptide; sodium caprylate or the combination of sodium caprylate and the sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of sodium caprylate used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0275] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving semaglutide; sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients; b) mixing together the semaglutide, the sodium caprylate or the combination of sodium caprylate and the sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC); and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of sodium caprylate used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0276] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a peptide; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0277] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; b) granulating a peptide with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; and the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg.

[0278] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0279] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0280] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0281] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0282] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0283] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the sodium N- (8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0284] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the sodium N- (8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets, preferably using direct compression; and e) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0285] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients; b) mixing together the peptide; the sodium caprylate or the combination of sodium caprylate and the sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC); and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of sodium caprylate used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1 .5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0286] Another embodiment of the present disclosure relates to a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) sieving semaglutide; sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients; b) mixing together the semaglutide; the sodium caprylate or the combination of sodium caprylate and the sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC); and the optionally one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets, preferably using direct compression; and e) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylic acid (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of sodium caprylate used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of semaglutide used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0287] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a peptide; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the peptide used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1 .5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0288] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2-hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 00 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0289] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6- C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0290] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a GLP-1 peptide agonist selected from semaglutide and pharmaceutically acceptable salts thereof as the sole permeability enhancers; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid; and optionally one or more excipients by dry granulation; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0291] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6- C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0292] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a GLP-1 peptide agonist selected from semaglutide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6- C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0293] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0294] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a GLP-1 peptide agonist selected from semaglutide and pharmaceutically acceptable salts thereof; a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0295] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof; sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients by dry granulation; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of sodium caprylate used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1 .5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0296] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating semaglutide; sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients by dry granulation; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of sodium caprylate used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of semaglutide used in step a) is 0.5 to 60 mg, preferably 1 to 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0297] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; b) granulating a peptide with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the peptide used in step b) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0298] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a

[0299] C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6- C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) granulating a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, beinaglutide, efpeglenatide, coumaglutide, tirzepatide and pharmaceutically acceptable salts thereof with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step b) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0300] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a

[0301] C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6- C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) granulating a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step b) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0302] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a

[0303] C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6- C9 fatty acid or a salt thereof is selected from sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, potassium nonanoate, ammonium caproate, ammonium heptanoate, ammonium caprylate, or ammonium nonanoate; b) granulating a GLP-1 peptide agonist selected from semaglutide and pharmaceutically acceptable salts thereof with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step b) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0304] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a

[0305] C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6- C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) granulating a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step b) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0306] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a

[0307] C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid selected from sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC), potassium N-(8-(2- hydroxybenzoyl)amino)caprylic acid and ammonium N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6- C9 fatty acid or a salt thereof selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) granulating a GLP-1 peptide agonist selected from semaglutide and pharmaceutically acceptable salts thereof with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step b) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0308] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6-C9 fatty acid or a salt thereof selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) granulating a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step b) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0309] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and sodium N-(8-(2- hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients by dry granulation; wherein the C6-C9 fatty acid or a salt thereof is selected from sodium caprylate, potassium caprylate and ammonium caprylate; b) granulating semaglutide and pharmaceutically acceptable salts thereof with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of semaglutide and pharmaceutically acceptable salts thereof used in step b) is 0.5 to 60 mg, preferably 1 to 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0310] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients by dry granulation; b) granulating a GLP-1 peptide agonist selected from semaglutide, liraglutide, exenatide, exendin-4 and tirzepatide and pharmaceutically acceptable salts thereof with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of sodium caprylate used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of the GLP-1 peptide agonist used in step b) is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1 .5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0311] In another embodiment of the present disclosure is a method of preparing a pharmaceutical formulation as described herein, wherein the method comprises the steps of: a) granulating sodium caprylate or the combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) as the sole permeability enhancers; and optionally one or more excipients by dry granulation; b) granulating semaglutide with one or more excipients; c) mixing the granules from steps a) and b); and d) pressing the mixed granules from step c) into tablets; wherein preferably, the weight of sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) used in step a) is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg; the weight of sodium caprylate used in step a) is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, preferably 150 mg to 300 mg, such as 150 mg or 300 mg; and the weight of semaglutide used in step b) is 0.5 to 60 mg, preferably 1 to 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0312] In one embodiment, dry granulation is carried out using roller compaction.

[0313] Uses of formulation

[0314] A third aspect of the present disclosure is a pharmaceutical formulation comprising: a peptide; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers, for use in the treatment of diabetes mellitus.

[0315] One embodiment of the third aspect of the present disclosure is a pharmaceutical formulation comprising: a peptide; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers, for use in the treatment of obesity.

[0316] One embodiment of the third aspect of the present disclosure, is a pharmaceutical formulation comprising: semaglutide; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers, for use in the treatment of diabetes mellitus.

[0317] One embodiment of the third aspect of the present disclosure, is a pharmaceutical formulation comprising: semaglutide; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers, for use in the treatment of obesity. Another embodiment of the third aspect of the present disclosure, is a pharmaceutical formulation comprising: semaglutide; and sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers, for use in the treatment of diabetes mellitus.

[0318] Another embodiment of the third aspect of the present disclosure, is a pharmaceutical formulation comprising: semaglutide; and sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers, for use in the treatment of obesity.

[0319] The diabetes mellitus may be type 1 diabetes mellitus or type 2 diabetes mellitus.

[0320] Additional aspects of the present disclosure

[0321] The present disclosure can also be described with reference to the following aspects:

[0322] Aspects of the present disclosure-.

[0323] <1 >. A pharmaceutical formulation comprising: a peptide; and a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N- (8-(2-hydroxybenzoyl)amino)caprylic acid.

[0324] <2>. The pharmaceutical formulation according to aspect <1 >, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers in the pharmaceutical formulation.

[0325] <3>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof is the sole permeability enhancer in the pharmaceutical formulation.

[0326] <4>. The pharmaceutical formulation according to aspect <1 > or <2>, wherein a C6- C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers in the pharmaceutical formulation. <5>. A pharmaceutical formulation according to aspect <1 > wherein the pharmaceutical formulation comprises: a peptide; and a permeability enhancer selected from the group consisting of: a C6-C9 fatty acid or a salt thereof, or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid.

[0327] <6>. The pharmaceutical formulation according to any of the preceding aspects, wherein the peptide is a GLP-1 peptide agonist.

[0328] <7>. The pharmaceutical formulation according to any of the preceding aspects, wherein the peptide is a GLP-1 peptide agonist selected from the group consisting of semaglutide, liraglutide, tirzepatide, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, and pharmaceutically acceptable salts thereof.

[0329] <8>. The pharmaceutical formulation according to any of the preceding aspects, wherein the peptide is semaglutide.

[0330] <9>. The pharmaceutical formulation according to any of the preceding aspects, wherein the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is selected from the group consisting of the sodium, potassium and ammonium salt.

[0331] <10>. The pharmaceutical formulation according to any of the preceding aspects, wherein the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is sodium N-(8-(2- hydroxybenzoyl)amino)caprylate.

[0332] <11 >. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof is selected from the group consisting of caproic acid, caprylic acid, enthanoic acid and pelargonic acid.

[0333] <12>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof is selected from the group consisting of sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, and potassium nonanoate.

[0334] <13>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof is selected from the group consisting of sodium caprylate, potassium caprylate and ammonium caprylate.

[0335] <14>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof is selected from the group consisting of caprylic acid, sodium caprylate and potassium caprylate.

[0336] <15>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof is sodium caprylate.

[0337] <16>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof present in the pharmaceutical composition is selected from the group consisting of sodium caprylate.

[0338] <17>. The pharmaceutical formulation according to any of the preceding aspects, wherein the only C6-C9 fatty acid or a salt thereof present in the pharmaceutical composition is sodium caprylate.

[0339] <18>. The pharmaceutical formulation according to any of the preceding aspects, wherein when a C6-C9 fatty acid or a salt thereof is present in the pharmaceutical composition it is selected from the group consisting of sodium caprylate.

[0340] <19>. The pharmaceutical formulation according to any of the preceding aspects comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid.

[0341] <20>. The pharmaceutical formulation according to any of the preceding aspects comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers. <21 >. The pharmaceutical formulation according to any of the preceding aspects comprising: semaglutide; and sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate.

[0342] <22>. The pharmaceutical formulation according to any of the preceding aspects comprising: semaglutide; and sodium caprylate or a combination of sodium caprylate and sodium N-(8-(2-hydroxybenzoyl)amino)caprylate as the sole permeability enhancers.

[0343] <23>. The pharmaceutical formulation according to any of the preceding aspects, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5.

[0344] <24>. The pharmaceutical formulation according to any of the preceding aspects, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 2:1 to 1 :4.

[0345] <25>. The pharmaceutical formulation according to any of the preceding aspects, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :4.

[0346] <26>. The pharmaceutical formulation according to any of the preceding aspects, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :3.

[0347] <27>. The pharmaceutical formulation according to any of the preceding aspects, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :2.

[0348] <28>. The pharmaceutical formulation according to any of the preceding aspects, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 or 1 :2.

[0349] <29>. The pharmaceutical formulation according to any of the preceding aspects, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 .

[0350] <30>. The pharmaceutical formulation according to any of the preceding aspects, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :2.

[0351] <31 >. The pharmaceutical formulation according to any of the preceding aspects comprising: a GLP-peptide agonist; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5.

[0352] <32>. The pharmaceutical formulation according to any of the preceding aspects comprising: a GLP-peptide agonist; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5.

[0353] <33>. The pharmaceutical formulation according to any of the preceding aspects comprising: semaglutide; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; wherein when the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5.

[0354] <34>. The pharmaceutical formulation according to any of the preceding aspects comprising: semaglutide; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5.

[0355] <35>. The pharmaceutical formulation according to any of the preceding aspects comprising: a GLP-peptide agonist; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 2:1 to 1 :4.

[0356] <36>. The pharmaceutical formulation according to any of the preceding aspects comprising: semaglutide; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 2:1 to 1 :4.

[0357] <37>. The pharmaceutical formulation according to any of the preceding aspects comprising: a GLP-peptide agonist; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1:4.

[0358] <38>. The pharmaceutical formulation according to any of the preceding aspects comprising: semaglutide; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :4.

[0359] <39>. The pharmaceutical formulation according to any of the preceding aspects comprising: a GLP-peptide agonist; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :3.

[0360] <40>. The pharmaceutical formulation according to any of the preceding aspects comprising: semaglutide; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :3.

[0361] <41 >. The pharmaceutical formulation according to any of the preceding aspects comprising: a GLP-peptide agonist; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :2. <42>. The pharmaceutical formulation according to any of the preceding aspects comprising: semaglutide; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :2.

[0362] <43>. The pharmaceutical formulation according to any of the preceding aspects comprising: a GLP-peptide agonist; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 or 1 :2.

[0363] <44>. The pharmaceutical formulation according to any of the preceding aspects comprising: semaglutide; sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 or 1 :2.

[0364] <45>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, preferably sodium N-(8-(2-hydroxybenzoyl)amino)caprylate, in the pharmaceutical formulation is 0 to 400 mg.

[0365] <46>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, preferably sodium N-(8-(2-hydroxybenzoyl)amino)caprylate, in the pharmaceutical formulation is 50 to 400 mg.

[0366] <47>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, preferably sodium N-(8-(2-hydroxybenzoyl)amino)caprylate, in the pharmaceutical formulation is 100 to 350 mg.

[0367] <48>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, preferably sodium N-(8-(2-hydroxybenzoyl)amino)caprylate, in the pharmaceutical formulation is 100 to 300 mg.

[0368] <49>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, preferably sodium N-(8-(2-hydroxybenzoyl)amino)caprylate, in the pharmaceutical formulation is 100 to 200 mg.

[0369] <50>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, preferably sodium N-(8-(2-hydroxybenzoyl)amino)caprylate, in the pharmaceutical formulation is 150 mg.

[0370] <51 >. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg.

[0371] <52>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg.

[0372] <53>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 250 to 750 mg.

[0373] <54>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 to 600 mg.

[0374] <55>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 to 450 mg.

[0375] <56>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 or 450 mg.

[0376] <57>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 800 mg.

[0377] <58>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 600 mg.

[0378] <59>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 500 mg.

[0379] <60>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 50 to 400 mg.

[0380] <61 >. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 100 to 350 mg.

[0381] <62>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 150 to 300 mg.

[0382] <63>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the C6-C9 fatty acid or a salt thereof in the pharmaceutical formulation is 150 mg or 300 mg.

[0383] <64>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0384] <65>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0385] <66>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :4.

[0386] <67>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :3.

[0387] <68>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 200 to 800 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :2.

[0388] <69>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 250 to 750 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2. <70>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 250 to 750 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :4.

[0389] <71 >. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 250 to 750 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :3.

[0390] <72>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 250 to 750 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :2.

[0391] <73>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 to 600 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0392] <74>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 to 600 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :4.

[0393] <75>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 to 600 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :3.

[0394] <76>. The pharmaceutical formulation according to any of the preceding aspects, wherein the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 300 to 600 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :2.

[0395] <77>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0396] <78>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 200 to 800 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0397] <79>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 200 to 800 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 2:1 to 1 :4.

[0398] <80>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 200 to 800 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :4.

[0399] <81 >. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 200 to 800 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :3.

[0400] <82>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 200 to 800 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :2.

[0401] <83>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 250 to 750 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0402] <84>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 250 to 750 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 2:1 to 1 :4.

[0403] <85>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 250 to 750 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :4.

[0404] 86>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 250 to 750 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :3.

[0405] <87>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 250 to 750 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :2.

[0406] <88>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 300 to 600 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0407] <89>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 300 to 600 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 2:1 to 1 :4.

[0408] <90>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 300 to 600 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :4.

[0409] <91 >. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 300 to 600 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :3.

[0410] <92>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 300 to 600 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :2.

[0411] <93>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 300 to 450 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

[0412] <94>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 300 to 450 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 2:1 to 1 :4.

[0413] <95>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 300 to 450 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :4.

[0414] <96>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 300 to 450 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :3.

[0415] <97>. The pharmaceutical formulation according to any of the preceding aspects, comprising: a GLP-1 peptide agonist; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 300 to 450 mg; and wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :2. <98>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising one or more excipients selected from a diluent, a disintegrant, a binder, a lubricant, an alkalizing agent, a water-soluble agent and anti-oxidant.

[0416] <99>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising one or more excipients selected from a diluent, a binder and a lubricant.

[0417] <100>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising one or more diluents selected from microcrystalline cellulose, maltodextrin, sucrose, xylitol, lactose, dextrose, sorbitol, dextrates, lactitol, kaolin, mannitol, starlac, starch, modified starches, dibasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium sulfate, magnesium carbonate, and magnesium oxide.

[0418] <101 >. The pharmaceutical formulation according to any of the preceding aspects additionally comprising one or more diluents selected from silicified microcrystalline cellulose, maltodextrin, sucrose, Xylitol, microcrystalline cellulose, and lactose monohydrate.

[0419] <102>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising microcrystalline cellulose.

[0420] <103>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising one or more binders selected from cellulose and its derivatives including ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose and hydroxyethyl cellulose, carboxymethyl cellulose; gelatin, liquid glucose; starch and its derivatives; hydrocolloids; sugars; polyvinyl pyrrolidone, sodium alginate, acacia, alginic acid and tragacanth.

[0421] <104>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising polyvinyl pyrrolidone.

[0422] <105>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising one or more disintegrants selected from cellulose and its derivatives including low-substituted hydroxypropyl cellulose; cross-linked polyvinylpyrrolidone; polyvinylpyrrolidone; cross-linked sodium carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose; sodium starch glycolate; ion-exchange resins; starch and modified starches; and formalin-casein.

[0423] <106>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising one or more lubricants selected from calcium stearate, magnesium stearate, glycerol behenate, mineral oil, polyethylene glycol, sodium stearyl fumarate, stearic acid, talc, vegetable oil, and zinc stearate.

[0424] <107>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising one or more glidants selected from talc, silicon dioxide and cornstarch.

[0425] <108>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising magnesium stearate.

[0426] <109>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising one or more excipients selected from the group consisting of silicified microcrystalline cellulose, maltodextrin, sucrose, Xylitol, microcrystalline cellulose, lactose monohydrate, polyvinylpyrrolidone, and magnesium stearate.

[0427] <110>. The pharmaceutical formulation according to any of the preceding aspects additionally comprising one or more excipients selected from the group consisting of microcrystalline cellulose, polyvinylpyrrolidone, and magnesium stearate.

[0428] <111 >. The pharmaceutical formulation according to any of the preceding aspects, wherein the pharmaceutical formulation does not contain sodium caprate or L-Arginine.

[0429] <112>. The pharmaceutical formulation according to any of the preceding aspects, wherein the weight of the peptide in the pharmaceutical formulation is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, Ill such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0430] <113>. The pharmaceutical formulation according to any of the preceding aspects, wherein the peptide is a GLP-1 peptide agonist and the weight of the GLP-1 peptide agonist in the pharmaceutical formulation is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0431] <114>. The pharmaceutical formulation according to any of the preceding aspects, wherein the peptide is semaglutide and the weight of semaglutide in the pharmaceutical formulation is 0.5 to 60 mg, preferably 1 to 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

[0432] <115>. The pharmaceutical formulation according to any of the preceding aspects, wherein the pharmaceutical formulation is a solid oral formulation.

[0433] <116>. The pharmaceutical formulation according to any of the preceding aspects, wherein the pharmaceutical formulation is a solid oral formulation in the form of a capsule or a tablet.

[0434] <117>. The pharmaceutical formulation according to any of the preceding aspects, wherein the pharmaceutical formulation is a solid oral formulation in the form of a tablet.

[0435] <118>. A method of preparing a pharmaceutical formulation according to any of the preceding aspects, wherein the method comprises the steps of: a) sieving the peptide; the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally one or more excipients; b) mixing together the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients of step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets.

[0436] <119>. A method of preparing a pharmaceutical formulation according to aspect <118>, wherein step c) comprises the steps of: (i) compacting the mixed powder from step b), (ii) sieving the compacted powder, (iii) optionally adding extragranular excipients, and (iv) optionally coating.

[0437] <120>. A method of preparing a pharmaceutical formulation according to any one of aspects <1 > to <117>, wherein the method comprises the steps of: a) granulating the peptide; the C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally one or more excipients by dry granulation; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets.

[0438] <121 >. A method of preparing a pharmaceutical formulation according to any one of aspects <1 > to <117>, wherein the method comprises the steps of: a) granulating a C6-C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid; and optionally one or more excipients by dry granulation; b) granulating the peptide with one or more excipients; c) mixing the granules of steps a) and b); d) pressing the mixed granules from step c) into tablets; and e) optionally coating the tablets.

[0439] <122>. The method according to any one of aspects <118> to <121 >, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0440] <123>. The method according to any one of aspects <118> to <122>, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is 2:1 to 1 :4.

[0441] <124>. The method according to any one of aspects <118> to <123>, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is 1 :1 to 1 :4.

[0442] <125>. The method according to any one of aspects <118> to <124>, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is 1 :1 to 1 :3.

[0443] <126>. The method according to any one of aspects <118> to <125>, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof in step a) is 1 :1 to 1 :2.

[0444] <127>. The method according to any one of aspects <118> to <126>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in step a).

[0445] <128>. The method according to any one of aspects <118> to <127>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in step a) in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg. <129>. The method according to any one of aspects <118> to <128>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in step a) in a weight of 250 to 750 mg.

[0446] <130>. The method according to any one of aspects <118> to <129>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in step a) in a weight of 300 to 600 mg.

[0447] <131 >. The method according to any one of aspects <118> to <130>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in step a) in a weight of 300 to 450 mg.

[0448] <132>. The method according to any one of aspects <118> to <131 >, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in step a) in a weight of 300 mg or 450 mg.

[0449] <133>. The method according to any one of aspects <118> to <132>, wherein the peptide is a GLP-1 peptide agonist.

[0450] <134>. The method according to any one of aspects <118> to <133>, wherein the peptide is selected from the group consisting of semaglutide, liraglutide, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, and pharmaceutically acceptable salts thereof.

[0451] <135>. The method according to any one of aspects <118> to <134>, wherein the peptide is semaglutide.

[0452] <136>. The method according to any one of aspects <118> to <135>, wherein the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is selected from the group consisting of the sodium, potassium and ammonium salt. <137>. The method according to any one of aspects <118> to <136>, wherein the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is sodium N-(8-(2- hydroxybenzoyl)amino)caprylate.

[0453] <138>. The method according to any one of aspects <118> to <137>, wherein the C6- C9 fatty acid or a salt thereof is selected from the group consisting of caproic acid, caprylic acid, enthanoic acid and pelargonic acid.

[0454] <139>. The method according to any one of aspects 118> to <138>, wherein the C6- C9 fatty acid or a salt thereof is selected from the group consisting of sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, and potassium nonanoate.

[0455] <140>. The method according to any one of aspects <118> to <139>, wherein the C6- C9 fatty acid or a salt thereof is selected from the group consisting of sodium caprylate, potassium caprylate and ammonium caprylate.

[0456] <141 >. The method according to any one of aspects <118> to <140>, wherein the C6- C9 fatty acid or a salt thereof is selected from the group consisting of caprylic acid, sodium caprylate and potassium caprylate.

[0457] <142>. The method according to any one of aspects <118> to <141 >, wherein the C6- C9 fatty acid or a salt thereof is sodium caprylate.

[0458] <143>. The method according to any one of aspects <118> to <142>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 0 to 400 mg.

[0459] <144>. The method according to any one of aspects <118> to <143>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 50 to 400 mg.

[0460] <145>. The method according to any one of aspects <118> to <144>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 100 to 350 mg.

[0461] <146>. The method according to any one of aspects <118> to <145>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 100 to 300 mg.

[0462] <147>. The method according to any one of aspects <118> to <146>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 100 to 200 mg.

[0463] <148>. The method according to any one of aspects <118> to <147>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid used in step a) is 150 mg.

[0464] <149>. The method according to any one of aspects <118> to <148>, wherein the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 800 mg.

[0465] <150>. The method according to any one of aspects <118> to <149>, wherein the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 50 to 600 mg.

[0466] <151 >. The method according to any one of aspects <118> to <150>, wherein the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 100 to 350 mg.

[0467] <152>. The method according to any one of aspects <118> to <151 >, wherein the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 150 mg to 300 mg.

[0468] <153>. The method according to any one of aspects <118> to <152>, wherein the weight of the C6-C9 fatty acid or a salt thereof used in step a) is 150 mg or 300 mg.

[0469] <154>. The method according to any one of aspects <118> to <153>, wherein the weight of the peptide is 0.5 to 60 mg.

[0470] <155>. The method according to any one of aspects <118> to <154>, wherein the weight of the peptide is 1 to 50 mg, such as 50 mg.

[0471] <156>. The method according to any one of aspects <118> to <155>, wherein the weight of the peptide is 1 to 30 mg.

[0472] <157>. The method according to any one of aspects <118> to <156>, wherein the weight of the peptide is 1 to 25 mg, such as 25 mg.

[0473] <158>. The method according to any one of aspects <118> to <157>, wherein the weight of the peptide is 1 to 20 mg.

[0474] <159>. The method according to any one of aspects <118> to <158>, wherein the weight of the peptide is 1 to 14 mg.

[0475] <160>. The method according to any one of aspects <118> to <159>, wherein the weight of the peptide is 3 to 14 mg.

[0476] <161 >. The method according to any one of aspects <118> to <160>, wherein the weight of the peptide is 1 .5, 3, 4, 7, 9 or 14 mg.

[0477] <162>. The pharmaceutical formulation according to any one of aspects <1 > to <117>, for use in the treatment of diabetes mellitus.

[0478] <163>. The pharmaceutical formulation according to any one of aspects <1 > to <117>, for use in the treatment of obesity.

[0479] <164>. The pharmaceutical formulation according to any one of aspects <1 > to <117>, for use in the treatment of diabetes mellitus, wherein the peptide is semaglutide.

[0480] <165>. The pharmaceutical formulation according to any one of aspects <1 > to <117>, for use in the treatment of obesity, wherein the peptide is semaglutide.

[0481] <166>. A method of preparing a pharmaceutical formulation according to any one of aspects <1 > to <117>, wherein the method comprises the steps of: a) sieving a peptide; b) mixing the sieved peptide with a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and optionally one or more excipients; c) granulating the peptide; the C6-C9 fatty acid or a salt thereof or the combination of the C6-C9 fatty acid or a salt thereof and the salt of N-(8- (2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients by dry granulation; d) adding a lubricant to the granulated mixture of step c); e) pressing the granules from step d) into tablets; and f) optionally coating the tablets.

[0482] <167>. A method of preparing a pharmaceutical formulation according to any one of aspects <1 > to <117>, wherein the method comprises the steps of: a) mixing together a C6-C9 fatty acid or a salt thereof or a combination of a C6-C9 fatty acid or a salt thereof and a salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers; and a lubricant; and optionally one or more additional excipients; b) granulating the mixture of step a) by dry granulation; c) mixing the granulated mixture of step b) with a peptide and optionally one or more additional excipients; d) adding a lubricant to the mixture of step c); e) pressing the granules from step d) into tablets; and f) optionally coating the tablets.

[0483] <168>. The method according to any one of aspects <166> to <167>, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 3:1 to 1 :5, preferably 2:1 to 1 :4, preferably 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably, 1 :1 to 1 :2.

[0484] <169>. The method according to any one of aspects <166> to <168>, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 2:1 to 1 :4.

[0485] <170>. The method according to any one of aspects <166> to <169>, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :4.

[0486] <171 >. The method according to any one of aspects <166> to <170>, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :3.

[0487] <172>. The method according to any one of aspects <166> to <171 >, wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and the C6-C9 fatty acid or a salt thereof is 1 :1 to 1 :2.

[0488] <173>. The method according to any one of aspects <166> to <172>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in the method.

[0489] <174>. The method according to any one of aspects <166> to <173>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in a weight of 200 to 800 mg, preferably 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg.

[0490] <175>. The method according to any one of aspects <166> to <174>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in a weight of 250 to 750 mg. <176>. The method according to any one of aspects <166> to <175>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in a weight of 300 to 600 mg.

[0491] <177>. The method according to any one of aspects <166> to <176>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in a weight of 300 to 450 mg.

[0492] <178>. The method according to any one of aspects <166> to <177>, wherein the C6- C9 fatty acid or a salt thereof or the combination of a C6-C9 fatty acid or a salt thereof and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid are the sole permeability enhancers present in a weight of 300 mg or 450 mg.

[0493] <179>. The method according to any one of aspects <166> to <178>, wherein the peptide is a GLP-1 peptide agonist.

[0494] <180>. The method according to any one of aspects <166> to <179>, wherein the peptide is selected from the group consisting of semaglutide, liraglutide, lixisenatide, taspoglutide, albiglutide, dulaglutide, langlenatide, and pharmaceutically acceptable salts thereof.

[0495] <181 >. The method according to any one of aspects <166> to <180>, wherein the peptide is semaglutide.

[0496] <182>. The method according to any one of aspects <166> to <181 >, wherein the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is selected from the group consisting of the sodium, potassium and ammonium salt.

[0497] <183>. The method according to any one of aspects <166> to <182>, wherein the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is sodium N-(8-(2- hydroxybenzoyl)amino)caprylate. <184>. The method according to any one of aspects <166> to <183>, wherein the C6- C9 fatty acid or a salt thereof is selected from the group consisting of caproic acid, caprylic acid, enthanoic acid and pelargonic acid.

[0498] <185>. The method according to any one of aspects <166> to <184>, wherein the C6- C9 fatty acid or a salt thereof is selected from the group consisting of sodium caproate, sodium heptanoate, sodium caprylate, sodium nonanoate, potassium caproate, potassium heptanoate, potassium caprylate, and potassium nonanoate.

[0499] <186>. The method according to any one of aspects <166> to <185>, wherein the C6- C9 fatty acid or a salt thereof is selected from the group consisting of sodium caprylate, potassium caprylate and ammonium caprylate.

[0500] <187>. The method according to any one of aspects <166> to <186>, wherein the C6- C9 fatty acid or a salt thereof is selected from the group consisting of caprylic acid, sodium caprylate and potassium caprylate.

[0501] <188>. The method according to any one of aspects <166> to <187>, wherein the C6- C9 fatty acid or a salt thereof is sodium caprylate.

[0502] <189>. The method according to any one of aspects <166> to <188>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is 0 to 400 mg.

[0503] <190>. The method according to any one of aspects <166> to <189>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is 50 to 400 mg.

[0504] <191 >. The method according to any one of aspects <166> to <190>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is 100 to 350 mg.

[0505] <192>. The method according to any one of aspects <166> to <191 >, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is 100 to 300 mg.

[0506] <193>. The method according to any one of aspects <166> to <192>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is 100 to 200 mg. <194>. The method according to any one of aspects <166> to <193>, wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is 150 mg.

[0507] <195>. The method according to any one of aspects <166> to <194>, wherein the weight of the C6-C9 fatty acid or a salt thereof is 50 to 800 mg.

[0508] <196>. The method according to any one of aspects <166> to <195>, wherein the weight of the C6-C9 fatty acid or a salt thereof is 50 to 600 mg.

[0509] <197>. The method according to any one of aspects <166> to <196>, wherein the weight of the C6-C9 fatty acid or a salt thereof is 100 to 350 mg.

[0510] <198>. The method according to any one of aspects <166> to <197>, wherein the weight of the C6-C9 fatty acid or a salt thereof is 150 mg to 300 mg.

[0511] <199>. The method according to any one of aspects <166> to <198>, wherein the weight of the C6-C9 fatty acid or a salt thereof is 150 mg or 300 mg.

[0512] <200>. The method according to any one of aspects <166> to <199>, wherein the weight of the peptide is 0.5 to 60 mg.

[0513] <201 >. The method according to any one of aspects <166> to <200>, wherein the weight of the peptide is 1 to 50 mg, such as 50 mg.

[0514] <202>. The method according to any one of aspects <166> to <201 >, wherein the weight of the peptide is 1 to 30 mg.

[0515] <203>. The method according to any one of aspects <166> to <202>, wherein the weight of the peptide is 1 to 25 mg, such as 25 mg.

[0516] <204>. The method according to any one of aspects <166> to <203>, wherein the weight of the peptide is 1 to 20 mg. <205>. The method according to any one of aspects <166> to <204>, wherein the weight of the peptide is 1 to 14 mg.

[0517] <206>. The method according to any one of aspects <166> to <205>, wherein the weight of the peptide is 3 to 14 mg.

[0518] <207>. The method according to any one of aspects <166> to <206>, wherein the weight of the peptide is 1 .5, 3, 4, 7, 9 or 14 mg.

[0519] <208>. The method according to any one of aspects <166> to <207>, wherein the one or more excipients comprises a diluent selected from microcrystalline cellulose, maltodextrin, sucrose, xylitol, lactose, dextrose, sorbitol, dextrates, lactitol, kaolin, mannitol, starlac, starch, modified starches, dibasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium sulfate, magnesium carbonate, and magnesium oxide.

[0520] <209>. The method according to any one of aspects <166> to <208>, wherein the one or more excipients comprises a diluent selected from silicified microcrystalline cellulose, maltodextrin, sucrose, Xylitol, microcrystalline cellulose, and lactose monohydrate.

[0521] <210>. The method according to any one of aspects <166> to <209>, wherein the one or more excipients comprises a diluent selected from microcrystalline cellulose.

[0522] <211 >. The method according to any one of aspects <166> to <210> , wherein the one or more excipients comprises a binder selected from cellulose and its derivatives including ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose and hydroxyethyl cellulose, carboxymethyl cellulose; gelatin, liquid glucose; starch and its derivatives; hydrocolloids; sugars; polyvinyl pyrrolidone, sodium alginate, acacia, alginic acid and tragacanth.

[0523] <212>. The method according to any one of aspects <166> to <211 >, wherein the one or more excipients comprises a binder selected from polyvinyl pyrrolidone. <213>. The method according to any one of aspects <166> to <212>, wherein the one or more excipients are polyvinyl pyrrolidone and microcrystalline cellulose.

[0524] <214>. The method according to any one of aspects <167> to <207>, wherein no additional excipients are present in step a) and / or step c).

[0525] <215>. The method according to any one of aspects <167> to <207> and <214>, wherein the lubricant is selected from the group consisting of calcium stearate, magnesium stearate, glycerol behenate, mineral oil, polyethylene glycol, sodium stearyl fumarate, stearic acid, talc, vegetable oil, and zinc stearate.

[0526] <216>. The method according to any one of aspects <167> to <207> and <214> to <215>, wherein the lubricant is magnesium stearate.

[0527] <217>. The method according to any one of aspects <167> to <207> and <214> to <216>, wherein about 50% by weight of the total weight of lubricant in the pharmaceutical formulation is used in step a); and about 50% by weight of the total weight of lubricant in the pharmaceutical formulation is used in step d).

[0528] <218>. The method according to any one of aspects <167> to <207> and <214> to <216>, wherein 2 mg of lubricant, preferably magnesium stearate, is used in step a); and 2 mg of lubricant, preferably magnesium stearate, is used in step d).

[0529] <219>. The pharmaceutical formulation according to any of aspects <1 > to <117>, wherein the pharmaceutical formulation does not contain a mucoadhesive and / or basifier.

[0530] EXAMPLES

[0531] Example 1 - preparation of samples (blends) of semaglutide with permeability enhancers The following blends were prepared by sieving the materials together, then mixing the materials with a mortar.

[0532] Table 1-1. Composition of Blends 1 to 9 Table 1-2. Composition of Blends 10 to 16 2 - Semaqlutide permeability across CaCo-2 cell monolayers, alone or in the i of SNAC, fatty acids (C8 or C10) or mixtures thereof

[0533] Blends 1 to 9 and 10 to 16 were then tested in a CaCo-2 study as described in Hubatsch et al. “Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers”, Nat. Protoc. (2007) 2, 2111 -9. The following materials were used:

[0534] - CaCo-2 -ATCC cells

[0535] - Eagle’s Minimum Essential Medium (EMEM) -ATCC

[0536] - Fetal BovineSerum(FBS) -ATCC

[0537] - Hank’s Balanced Salt Solution (HBSS) -ATCC

[0538] - Trypsin-EDTA -ATCC

[0539] - Phosphate Buffered Saline (PBS) -Sigma

[0540] - Penicillin - Streptomicin - Amphotericin-B - Sigma

[0541] - N-(2-hydroxyethyl)piperazine-N’-ethanesulfonic acid (HEPES) - Biowest

[0542] - Transwell polycarbonate membrane cell culture plates -Corning

[0543] The following equipment was used:

[0544] - Biological Safety Cabinet Class II, BioAir-TopSafel .2 -EuroClone

[0545] - Cell incubator Innova CO-170 -New Brunswick Scientific

[0546] - Millicell-ERS-2 voltohm-meter -Merck Millipore

[0547] - Precision balance, Mettler AE240 -Mettler Toledo

[0548] - Vortex - VELP Scientifica

[0549] - HPLC Agilent 1200 Series and DAD detector

[0550] Method'.

[0551] CaCo-2 cells were grown in EMEM medium supplemented with 20% heat-inactivated FBS, penicillin (100 U / mL), streptomycin (100 pg / mL) and amphotericin-B (0.25 pg / mL) in a humidified incubator with 5% CO2 and 95% air at the temperature of 37°C.

[0552] Two 12-well Transwell plates (12 mm diameter and over 0.4 pm) were prepared by seeding CaCo-2 cells (pass number 25) at a density of 1x10A5 cells per well. The experiment was performed after approximately 21 days post-confluence, a period necessary to spontaneously differentiate the cells into a polarized monolayer with microvilli and tight junctions.

[0553] The integrity of the monolayer was checked by measuring, every two days, the trans- epithelial electrical resistance (TEER) with the Millicell-ERS-2 volt-ohm meter. The experiment was performed with TEER values >300 Q-cm2 in HBSS (donor and receptor compartment).

[0554] The integrity of the monolayer has been confirmed at the end of the assay with TEER values >300 Q-cm2. For each formulation, 14 mg of Semaglutide diluted 1 :10 was used.

[0555] Each formulation was vortexed for 30 seconds prior to use for the assay.

[0556] Permeability samples were collected from the receiving side at different time points: 0, 15, 30, 60 and 120 minutes.

[0557] The collected samples were analyzed to quantify the concentration of Semaglutide using the liquid chromatography (HPLC) method coupled to a DAD detector (according to the protocol provided by InsudPharma).

[0558] The apparent permeability (Papp) of Semaglutide permeating from the donor side to the acceptor side was calculated according to the equation:

[0559] Papp= (V / A x T) x (dR / dD)

[0560] V: volume of the acceptor side (mL)

[0561] A: membrane area (cm2)

[0562] T: total permeation time (s) dR: concentration of Semaglutide in the acceptor side dD: concentration of Semaglutide in the donor side

[0563] The Papp value is expressed in cm / s.

[0564] All formulations were evaluated in triplicate (Mean ± SD, n=3)." Resu / ts

[0565] The results are shown in Figures 1 to 7 and are also shown in Table 2 below: Table 2. Semaglutide permeability across Caco-2 cell monolayers for Blends 1 to 16

[0566] Apparent permeability (Papp) of Semaglutide (1.4mg) in the Transwell model with CaCo-2 cells.

[0567] Blends 9 and 14 both formed a precipitate

[0568] The TEER values before the assay were between 700 and 900 0 cm2. At the end of the assay, it was confirmed that the TEER values remained >300 0 cm2.

[0569] The results presented in Table 2 show the calculated apparent permeability (Papp) of semaglutide. Calculated apparent permeability is a kinetic parameter which estimates the rate at which a compound crosses the membrane under specific conditions, normalized by area and concentration.

[0570] Figures 1 -7 show cumulative permeability or transport expressed as pg (micrograms) / ml accumulated. This shows the total amount of substance that has crossed the membrane during a given time interval, 120 min. This result is obtained by summing the amount permeated at each sampling point.

[0571] Figure 1 shows that far greater permeability of semaglutide was observed when SNAC was used in combination with sodium caprylate, than when using SNAC alone. Furthermore, when part of the SNAC in blend 2 was substituted with sodium caprylate (blend 5) the permeability of semaglutide was not affected. Although Blend 7 showed the highest permeability, it requires a large amount of sodium caprylate (C8) (600 mg) which would make it difficult to formulate an oral dosage form that could easily be administered orally.

[0572] Figure 2 shows a greater permeability of semaglutide when formulated with sodium caprylate (C8) and SNAC compared to being formulated with sodium caprate (C10) and SNAC. Furthermore, when using 300 mg of sodium caprate (C10) precipitation was observed. In contrast, when using the same amount of sodium caprylate (C8) (Blend 6) or even a higher amount (600 mg; Blend 7), no precipitation was observed.

[0573] Figure 3 shows that formulating semaglutide with either 150 mg SNAC alone or 150 mg sodium caprylate (C8) alone resulted in zero permeability of the peptide. However, when semaglutide was formulated with SNAC and sodium caprylate (C8), a synergistic effect was observed for the permeability of semaglutide.

[0574] Figure 4 shows that as the amount of either SNAC or sodium caprylate (C8) is increased, the permeability of semaglutide increases.

[0575] Figure 5 shows that binary blends of semaglutide and sodium caprylate (C8) (Blend 4) showed greater permeability than binary blends of semaglutide and SNAC (Blend 2). Furthermore, this effect was shown for Blends 15 and 16, which contain a greater amount of sodium caprylate (C8). Figure 6 shows that the inclusion of sodium caprylate in a blend containing semaglutide and SNAC increases permeability. This can be seen by comparing Blend 2 to each of Blends 5, 6, 10 and 11. Furthermore, this effect is also shown for blends containing 9 mg of semaglutide, i.e., Blends 12 and 13.

[0576] Figure 7 shows that Blend 6 containing SNAC and sodium caprylate (C8), showed greater permeability than Blends 9 and 14, containing SNAC and sodium caprate (C10).

[0577] *Blends 9 and 14 containing semaglutide, SNAC and sodium caprate (C10) did not form a homogenous solution and precipitation was observed.

[0578] Example 3 - oral solid pharmaceutical compositions of semaglutide comprising SNAC and sodium caprylate (C8)

[0579] Blends 1 , 2 and 7 as described in Example 1 were then combined with additives, which were sieved and mixed to prepare Formulations 1 , 2, and 3 respectively:

[0580] Table 3. Semaglutide formulations

[0581] Tablets were prepared from each of Formulations 1 , 2 and 3 by sieving and mixing all the materials together and pressing into tablets.

[0582] Example 4 - Clinical study Phase I, open label, randomized, pharmacokinetic, relative bioavailability study comparing the single dose administration of Test product and Reference product (as described in Table 4) in healthy volunteers. Plasma samples were assayed by a validated LCMS / MS method, which is specific for the determination of Semaglutide.

[0583] Table 4. Composition of test (T) and reference (R) tablets

[0584] Figure 8a shows the plasma concentration (ng / mL) of semaglutide in the patients’ blood plasma after a single dose administration of the test tablet or the reference tablet up to 504 hours after administration.

[0585] Figure 8b shows a section of the graph in Figure 8a up to 72 hours.

Claims

CLAIMS1 . A pharmaceutical formulation comprising: semaglutide; and sodium caprylate or a combination of sodium caprylate and a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers present in a weight of 200-800 mg; wherein when the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is present in the pharmaceutical formulation, the weight ratio of the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :5.

2. The pharmaceutical formulation according to any of the preceding claims, wherein the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is selected from the group consisting of the sodium, potassium and ammonium salt.

3. The pharmaceutical formulation according to any of the preceding claims, wherein the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is sodium N-(8-(2- hydroxybenzoyl)amino)caprylate.

4. The pharmaceutical formulation according to any of the preceding claims comprising: semaglutide and sodium caprylate; or semaglutide, sodium N-(8-(2- hydroxybenzoyl)amino)caprylate and sodium caprylate.

5. The pharmaceutical formulation according to any of the preceding claims, wherein the sodium caprylate or the combination of sodium caprylate and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid as the sole permeability enhancers are present in a weight of 250 to 750 mg, preferably 300 to 600 mg, preferably 300 to 450 mg, such as 300 mg or 450 mg.

6. The pharmaceutical formulation according to any of the preceding claims, wherein the weight ratio of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid and sodium caprylate is 1 :1 to 1 :4, preferably 1 :1 to 1 :3, more preferably 1 :1 to 1 :2.

7. The pharmaceutical formulation according to any of the preceding claims,wherein the weight of the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid in the pharmaceutical formulation is 0 to 400 mg, preferably 50 to 400 mg, preferably 100 to 350 mg, preferably 100 to 300 mg, preferably 100 to 200 mg, preferably 150 mg.

8. The pharmaceutical formulation according to any of the preceding claims, wherein the weight of sodium caprylate in the pharmaceutical formulation is 50 to 800 mg, preferably 50 to 600 mg, preferably 100 to 350 mg, more preferably 150 mg or 300 mg.

9. The pharmaceutical formulation according to any of the preceding claims, wherein the weight of the peptide in the pharmaceutical formulation is 0.5 to 60 mg, preferably 1 to 50 mg, such as 50 mg, preferably 1 to 30 mg, preferably 1 to 25 mg, such as 25 mg, preferably 1 to 20 mg, preferably 1 to 14 mg, such as 1.5, 3, 4, 7, 9 or 14 mg, preferably 3 to 14 mg.

10. The pharmaceutical formulation according to any of the preceding claims, wherein the pharmaceutical formulation is a solid oral formulation, preferably in the form of a capsule or a tablet.

11. A method of preparing the pharmaceutical formulation of any of the preceding claims, wherein the method comprises the steps of: a) sieving semaglutide; sodium caprylate or the combination of sodium caprylate and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; and optionally one or more excipients; b) mixing together semaglutide; sodium caprylate or the combination of sodium caprylate and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients, from step a); c) optionally compacting the mixed powder from step b); d) pressing the mixed powder from step b) or the compacted mixed powder from step c) into tablets; and e) optionally coating the tablets.

12. A method of preparing the pharmaceutical formulation of any one of claims 1 to 10, wherein the method comprises the steps of:a) granulating semaglutide; sodium caprylate or the combination of sodium caprylate and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; and optionally one or more excipients by dry granulation; b) pressing the granules from step a) into tablets; and c) optionally coating the tablets.

13. A method of preparing the pharmaceutical formulation of any one of claims 1 to 10, wherein the method comprises the steps of: a) sieving semaglutide; b) mixing the sieved semaglutide with sodium caprylate or the combination of sodium caprylate and the salt of N-(8-(2- hydroxybenzoyl)amino)caprylic acid; and optionally one or more excipients; c) granulating semaglutide; sodium caprylate or the combination of sodium caprylate and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; and optionally the one or more excipients by dry granulation; d) adding a lubricant to the granulated mixture of step c); e) pressing the granules from step d) into tablets; and f) optionally coating the tablets.

14. A method of preparing the pharmaceutical formulation of any one of claims 1 to 10, wherein the method comprises the steps of: a) mixing together sodium caprylate or the combination of sodium caprylate and the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; and a lubricant; and optionally one or more excipients; b) granulating the mixture of step a) by dry granulation; c) mixing the granulated mixture of step b) with semaglutide and optionally one or more excipients; d) adding a lubricant to the granulated mixture of step c); e) pressing the granules from step d) into tablets; and f) optionally coating the tablets.

15. The method according to claim 13 or 14, wherein the lubricant is magnesium stearate.

16. The method according to claim 14 or 15, wherein about 50% by weight of the total weight of lubricant in the pharmaceutical formulation is used in step a); and about 50% by weight of the total weight of lubricant in the pharmaceutical formulation is used in step d).

17. The pharmaceutical formulation according to any one of claims 1 to 10, for use in the treatment of diabetes mellitus or obesity.

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