Dry powder and liquid formulations

Abstract

Dry powder formulations of GLP-1 receptor agonists, such as semaglutide, dosage forms containing the same, and liquid feedstocks for preparing dosage forms, such as dry powers, that contain GLP-1 receptor agonists, are disclosed. Also disclosed are liquid formulations of GLP-1 receptor agonists, such as semaglutide.

Description

[0001] Dry Powder and Liquid Formulations FIELD The present invention relates to powder (especially dry powder) formulations comprising glucagon-like peptide-1 (GLP-1) receptor agonists (especially semaglutide), which are preferably for nasal delivery, or delivery by inhalation. The present invention further relates to dosage forms containing the same. The present invention further relates to liquid formulations of GLP-1 receptor agonists, such as semaglutide, and dosage forms containing the same. BACKGROUND Glucagon-like peptide-1 (GLP-1) receptor agonists form a class of active pharmaceutical ingredients (APIs) utilized to treat type 2 diabetes mellitus (T2DM) and obesity. Examples of GLP-1 agonists include: liraglutide, semaglutide, albiglutide and dulaglutide, which are classi^ed as long-acting agonists; and exenatide, beinaglutide and lixisenatide, which are classi^ed as short-acting agonists. Tirzepatide is a long-acting dual glucose- dependent insulinotropic polypeptide (GIP) receptor and a GLP-1 receptor agonist. These agonists are peptides typically having from 15 to 80 amino acid residues. For example, semaglutide and liraglutide are peptides comprising 31 amino acid residues. Semaglutide is currently marketed as a weekly injection, e.g. under the OzempicTMbrand name, or as a daily tablet, e.g. under the RybelsusTMbrand name, for weight loss and the treatment of type 2 diabetes (SNDD). However, the poor bioavailability and high cost entailed by oral and injectable dosage forms can make patient access a challenge. Meanwhile, complicated administration requirements can make compliance poor for a GLP-1 receptor agonist API, especially after initial weight loss. Furthermore, oral and injectable products can elicit severe sidee ects for a GLP-1 receptor agonist API.There is a need for alternative GLP-1 receptor agonist dosage forms that reduce or alleviate some or all of the above drawbacks to current injectable and tablet dosage forms. Additionally or alternatively, there is a need for improved GLP-1 receptor agonist delivery platforms. There is a need for platforms for nasal delivery of a GLP-1 receptor agonist, or for the delivery of a GLP-1 receptor agonist by inhalation, that may be formed (especially, when formed via spray drying or freeze drying methods) in good yields. There is a need for platforms for the nasal delivery of a GLP-1 receptor agonist, or for the delivery of a GLP-1 receptor agonist by inhalation, ideally in the form of a dry powder. Ideally, such powders would have a particle size appropriate for nasal delivery or delivery by inhalation. There is also a need for dry powder delivery platforms which, while being suited for the delivery of a GLP-1 receptor agonist, are also well suited to handling and processing, such as having low static, good ^owability and / or other features advantageous for handling. SUMMARY OF THE INVENTION The present inventors have realised that nasal delivery, and / or delivery by inhalation, mayavoid side e ects associated with current injectable and tablet dosages for a GLP-1receptor agonist (especially, semaglutide); and may improve a ordability, therebywidening the patient population able to receive the bene^ts that GLP-1 receptor agonists(especially semaglutide) may o er. Additionally or alternatively, such dosage forms mayo er an easy administration route, thereby enhancing compliance. Inhalableformulations may be an alternative way of achieving such bene^ts. In particular, formulations may be delivered nasally, or by inhalation, as either liquid or dry powder forms. Most preferably, dry powder formulations according to the present invention are suitable for nasal delivery. Due to the poor stability of some GLP-1 receptor agonists, especially semaglutide, dry powders have been identi^ed as a particularly promising nasal or inhalation dosage form. Routes to the manufacture of dry powders for nasal administration or inhalation may typically involve the formation of a liquid formulation which is converted into a dry powder through freeze drying or spray drying processes. There is a need for liquid formulations of semaglutide that are suitable for inhalation or nasal administration, and suitable feedstock for conversion into a dry powder for inhalation or nasal administration. The present inventors have also realised that dry powder formulations according to the present invention may usefully provide a delivery platform for nasal administration or inhalation, preferably nasal administration. Dry powder formulations according to the present invention may be combined with a GLP-1 receptor agonist and therefore serve as a useful drug delivery vehicle. The GLP-1 receptor agonist may be loaded onto the dry powder formulation during formation of the dry powder formulation itself, or the GLP-1 receptor agonist may be loaded onto the dry powder formulation after the dry powder formulation has been formed as a solid particulate powder. Preferably, the dry powder formulation with GLP-1 receptor agonist has a shelf-life stability of at least 3 days, preferably at least 3 weeks, most preferably at least 1 month so that the dry powder formulation may be stored for a signi^cant time before use, especially when stored at room temperature (e.g. no more than 30 °C and no less than 12 °C). The present inventors have investigated the suitability of various excipients, and combinations thereof, in dry powder formulations. One or more of the following properties may be preferred: that the dry powder is well suited to collection (e.g. in terms of static charge, aggregation, ^owability, adhesion to vessel); has a low moisture (especially, low water) content (ideally less than 5% w / w; e.g. analysed by Karl Fischer colorimetry); is a solid particulate powder having appropriately sized particles (for nasal delivery, ideally no more than 10 % v / v of the particles have a diameter of less than 10 µm; for delivery by inhalation, ideally the D50 of the solid particulate powder is in a range of 1-5 µm); has a good yield (when formed by spray drying from a solution in puri^ed water of the powder components; ideally, the yield is more than 15%, especially more than 50%); and / or has an appropriate glass transition temperature (e.g. analysed bymodulated di erential scanning calorimetry, mDSC); has a semaglutide contentdetermined by U-HPLC of at least 90% and / or a semaglutide content determined by SEC of at least 90%. In a ^rst aspect, the present invention provides a powder formulation (which is most preferably a dry powder formulation), the powder formulation preferably being in the form of a solid particulate powder, the powder formulation and comprising (or consisting) of:- at least one of a polymeric viscosity modi^er and a bulking agent,- a permeability enhancer;- an optional amino acid component; and- a glucagon-like peptide-1 (GLP-1) receptor agonist.Preferably the powder formulation is for nasal delivery or delivery by inhalation, most preferably nasal delivery. It will be understood that powder formulations for nasal delivery and delivery by inhalation require a de^ned particle size range (also referred to as a particle size distribution or ^PSD^). For example, nasal delivery powders should have a D10 of greater than about 10 µm (to avoid inhalation of particles); advantageously, no more than 10 % v / v of the particles have a diameter of less than 10 µm. Conversely, inhalable particles are typically in the range of 1-5 µm so as to enter into the airway. Optionally, the at least one of a polymeric viscosity modi^er and a bulking agent; the permeability enhancer; and the optional amino acid component, taken together, may be referred to as an excipient package. In the Examples hereinbelow, therefore, a description is provided of the manufacture of suitable excipient packages. The glucagon-like peptide-1 (GLP-1) receptor agonist may preferably be or comprise semaglutide. Optionally, the powder formulation of the ^rst aspect of the invention may comprise one or more binders. Optionally, the powder formulation of the ^rst aspect of the invention may comprise one or more bulking agents. It has been found that a combination of a polymeric viscosity modi^er and a permeability enhancer may be advantageous. Thus, the powder formulation of the ^rst aspect of the invention may comprise or consist of:- a polymeric viscosity modi^er;- a permeability enhancer;- an optional bulking agent; and- an optional amino acid component.It will be understood that the (preferably, dry) powder formulation of the ^rst aspect of the invention is suitable for delivery by inhalation, or nasal delivery. The powder may be further processed, for example weighed and packaged into a discrete dosage form for nasal delivery or inhalation. For example, the powder may be packaged in a handheld delivery device, such as an inhaler device, especially a dry powder inhaler device; or it may be packaged for use in a nebuliser. Optionally the inhaler or nebuliser may have or be packaged with a mouthpiece or mask. Thus, in a second aspect, the invention provides a dosage form for nasal delivery or inhalation, comprising the (preferably, dry) powder formulation of the ^rst aspect of the invention. The powder components disclosed herein may be present in amounts de^ned by % w / w. It will be appreciated that the % w / w amounts of components, when combined, will not sum to a value of more than 100. The present inventors have investigated the compatibility of various excipients in feedstock liquids to determine the interaction between the GLP-1 agonist, e.g. semaglutide, active pharmaceutical ingredient (API) and possible excipient molecules with the aim of identifying formulations with an advantageous stability pro^le, ideally formulations which are stable for at least 3 days when stored at 7 °C. In a third aspect, the present invention provides a liquid formulation comprising: (i) a GLP-1 agonist,(ii) an excipient package consisting of: (a) at least one of a polymericviscosity modi^er and a bulking agent, (b) an optional amino acid component, (c) a permeability enhancer, and (d) an optional binder; (iii) a liquid carrier;and optionally (iv) a bu er.The liquid formulation of the third aspect of the invention may comprises: (i) a GLP-1 agonist,(ii) an excipient package consisting of: (a) at least one of a polymericviscosity modi^er, a bulking agent and a binder, (b) an optional amino acid component, and (c) a permeability enhancer; and (iii) a liquid carrier. It has been found that in some embodiments a combination of a polymeric viscosity modi^er and a permeability enhancer is advantageous. Thus, the liquid formulation of the third aspect of the invention may comprise: (i) a GLP-1 agonist,(ii) an excipient package consisting of: (a) a polymeric viscosity modi^er andoptionally a bulking agent, (b) an optional amino acid component, (c) a permeability enhancer and (d) an optional binder; (iii) a liquid carrier;and optionally (iv) a bu er.The liquid formulations of the third aspect of the invention are advantageously suitable for use as feedstocks suitable for preparing dry power formulations for inhalation or nasal delivery, especially nasal delivery, by freeze drying or spray drying, preferably spray drying. Alternatively, the liquid formulations of the third aspect of the invention may be a constituent of, or a precursor to, a liquid dosage form suitable for inhalation or nasal delivery, especially nasal delivery. The liquid formulations of the third aspect of the invention may, for example, be used to prepare a powder formulation of the ^rst aspect of the present invention. In a fourth aspect, the present invention provides a liquid feedstock suitable for preparing a dry power, especially a dry powder according to the ^rst aspect of the invention. The liquid feedstock of the fourth aspect of the invention advantageous comprises the liquid formulation of the third aspect of the invention. The liquid feedstock may be suitable for manufacturing a dry powder formulation for nasal delivery by freeze drying or spray drying, preferably spray drying. In a ^fth aspect, the invention provides a dry powder dosage form for inhalation or nasal delivery, especially nasal delivery, formed from the liquid formulation of the third aspect of the invention or the liquid feedstock of the fourth aspect of the invention. In some embodiments, the dry powder dosage form of the ^fth aspect of the invention may comprise, or consist of, the powder formulation of the ^rst aspect of the invention. In a sixth aspect, the invention provides a dosage form for inhalation or nasal delivery, especially nasal delivery, comprising the liquid formulation of the third aspect of the invention. The liquid formulations, liquid feedstocks and dosage forms comprising the liquid formulation of the invention advantageously include essentially no surfactant, for example no more than 0.01 % w / w of surfactant, especially no more than 0.001 % w / w of surfactant, based on the total weight of the liquid formulation, feedstock or dosage form. DETAILED DESCRIPTION While the subject-matter of the present invention is described and illustrated below with reference to particular embodiments, it will be appreciated by those skilled in the art thatthe subject-matter lends itself to many di erent variations not speci^cally illustratedherein. By way of example only, certain possible variations will now be described. The formulations and dosage forms of the invention contain a GLP-1 receptor agonist (especially, semaglutide). Incretins are hormones secreted by cells in the midgut; they potentiate glucose- dependent insulin secretion. GLP-1 is a peptide and an endogenous incretin hormone, which is thought to promote glucose-dependent insulin synthesis and secretion, in the pancreatic islets. As used herein, ^endogenous^ GLP-1 means native human GLP-1, which is naturally produced in humans. GLP-1 may also decrease glucagon secretion, by acting on alpha cells in the pancreas. GLP-1 is further thought to act as a neurotransmitter, having a role in both the central nervous system (such that it may promote satiety and a loss of appetite) and on the peripheral nervous system. GLP-1 is understood to delay gastric emptying, inhibit pentagastrin, and reduce acid secretion stimulated by food ingestion. Glucagon-like peptide-1 (GLP-1) agonists are a class of medications utilized to treat type 2 diabetes mellitus (T2DM) and obesity. The GLP-1 agonist may be a peptide optionally having from 15 to 80 amino acid residues, such as from 20 to 50 amino acid residues. Suitable GLP-1 agonists include: liraglutide, semaglutide, albiglutide, dulaglutide, exenatide, beinaglutide, lixisenatide and tirzepatide. The GLP-1 agonist may be selected from liraglutide and semaglutide. A preferred GLP-1 agonist is semaglutide. The GLP-1 agonist may be present in the liquid formulations and feedstocks of the invention in a concentration of 1 to 20 mg / mL, such as a concentration of from 2 to 15 mg / mL. GLP-1 is thought to have cardiovascular bene^ts on blood pressure, the vascular endothelium, atherosclerosis progression and in^ammation, myocardial ischaemia, heart failure. Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 agonists, GLP-1 analogs, GLP-1DAs or incretin mimetics, are a class of peptides that (similarly to endogenous GLP-1) can stimulate the GLP-1 receptor. By mimicking the action of endogenous GLP-1, the class of GLP-1 receptor agonists may slow down gastric emptying, inhibit the release of glucagon, and stimulate insulin production, amongst other bene^ts, including those associated with endogenous GLP-1, described above. The GLP-1 receptor agonist in the powder formulations described herein may have an amino acid sequence identity with endogenous GLP-1 in a range of 80-99 %, such as in a range of 90-99 %, e.g.94 %. The GLP-1 receptor agonist may contain one or more (such as 1 to 4, 1 to 3, 1 to 2, or only one) conservative amino acid residue substitutions, compared to endogenous GLP-1 (^conservative^ having its normal meaning in the art thus referring to having similar physicochemical properties, compared to the corresponding endogenous amino acid residue(s)). The GLP-1 receptor agonist may contain one or more (such as 1 to 4, 1 to 3, 1 to 2, or only one) amino acid residues bearing a modi^ed side chain, compared to endogenous GLP- 1. The GLP-1 receptor agonist may contain one or more (such as 1 to 4, 1 to 3, 1 to 2, or only one) analogues of naturally occurring amino acid residues, such as homoarginine, benzyloxy-tyrosine, and / or -phenylalanine, not present in endogenous GLP-1. The GLP-1 receptor agonist preferably comprises or consists of semaglutide (CAS No. 910463-68-2). Semaglutide is a peptide having a chain length of 31 amino acid residues. Semaglutide is a long-acting GLP-1 agonist and has a 94 % amino acid sequence identity with endogenous GLP-1. The addition (compared to endogenous GLP-1) of a fatty diacidchain at position 26 of semaglutide enhances the a inity of semaglutide for albuminbinding resulting in reduced renal clearance; the replacement of alanine with - aminoisobutyric acid at position 8 (compared to endogenous GLP-1) makes semaglutide more resistant to enzymatic degradation. For the avoidance of doubt, as is usual in the art, amino acid residues (-NH-CHR-CO-) are numbered sequentially from the amino- terminal to the carboxyl-terminal end of the peptide chain.When delivered orally or intravenously, semaglutide may cause side e ects, such asgastrointestinal discomfort. Discontinuation of treatment with semaglutide may be associated with reversal of the cardiometabolic improvements and weight loss observed during the period of its administration, suggesting a need for ongoing treatment with semaglutide to maintain initial weight loss and cardiometabolic bene^ts. Without wishing to be bound by theory, it is thought that the presently described powderformulations may help to mitigate such side e ects and / or improve patient compliance.The GLP-1 receptor agonist (especially semaglutide) may be added to the powder formulation after the polymeric viscosity modi^er (if present); the bulking agent (if present); the permeability enhancer; and the amino acid (if present) have together been formed into a dry powder through spray drying or freeze drying a solution comprising them ^ i.e., the GLP-1 receptor agonist (especially semaglutide) may be added after an excipient package has been formed by spray drying or freeze drying. Alternatively, the GLP-1 receptor agonist (especially semaglutide) may be mixed with the polymeric viscosity modi^er (if present); the bulking agent (if present); the permeability enhancer; and the amino acid (if present), then the resultant mixture, including the GLP-1 receptor agonist (especially semaglutide), may be spray dried or freeze dried, to form the (dry) powder formulation. For the (preferably dry) powder formulation de^ned in accordance with the ^rst aspect of the invention, the GLP-1 receptor agonist (especially semaglutide) may be present in an amount in a range of 0.1-70 % w / w, such as 0.1-60 % w / w, especially 5-50 % w / w, such as 5-25 % w / w or 25-50 % w / w, based on the total weight of the powder formulation. Most preferably, semaglutide is present in an amount in a range of 5-25 % w / w based on the total weight of the powder formulation. The liquid formulation may comprise a GLP-1 receptor agonist in an amount such that when a dry powder is formed from the liquid formulation (i.e. the liquid formulation is a feedstock), the dry powder will have a GLP-1 receptor agonist amount as disclosed above. Preferably, in all aspects of the invention relating to a powder formulation, the powder is a dry powder. Thus, preferably, the powder formulation de^ned in accordance with the ^rst aspect of the invention is a dry powder formulation. Preferably when the powder is a dry powder, the powder takes the form of a (dry) solid particulate powder, i.e., dry, de^ned particles having a composition described herein. Optionally, at least 70, 80, 90 or 95 % v / v of the powder (e.g., substantially all of the powder) is formed of particles wherein each individual particle contains a mixture of the GLP-1 receptor agonist (such as semaglutide) with the other components of the powder (especially, with: the polymeric viscosity modi^er (if present); the bulking agent (if present); the permeability enhancer; and the amino acid (if present)). Alternatively, particles consisting or consisting substantially of the GLP-1 receptor agonist (such as semaglutide) may be disposed amongst further particles, the further particles comprising or consisting of said other components of the powder (i.e., particles of said other components of the powder may serve as a carrier particles alongside particles consisting or consisting substantially of the GLP-1 receptor agonist, such as semaglutide). Preferably, the solid particulate powder is in a form suitable for intranasal delivery. Alternatively, the solid particulate powder may be in a form suitable of inhalation. As used herein, the term ^dry powder^ may mean that the powder formulation has a moisture (i.e., liquid; especially, water) content of below 5 % w / w, preferably below 4 or 3 % w / w, based on the total weight of the powder formulation. Optionally, the powder formulation has a moisture (i.e., liquid; especially, water) content in a range of 1-5 % w / w. Moisture content may be measured by any suitable method in the art, such as by a colorimetric method. Suitably, especially when the moisture to be detected is water, the method may be a Karl Fischer method as is known in the art. The powder formulation may be a spray dried powder formulation. The powder formulation may be a freeze dried powder formulation. The powder formulation may be a dry powder formulation obtained without spray drying and without freeze drying, for example by mixing dry powdered components of the powder. The powder formulation may comprise one or more spray dried powder components, one or more freeze dried powder components, and / or one or more (non-spray dried, non-freeze dried) dry powdered components of the powder. The spray drying process may, optionally, comprise preparing a solution or suspension of the at least one of a polymeric viscosity modi^er and a bulking agent, a permeation enhancer, an optional amino acid component and GLP-1 receptor agonist as described herein and atomising the solution or suspension through a nozzle of a spray drying apparatus. The solution or suspension comprises a solvent, such as ethanol and / or water. The solution or suspension may be referred to as a feedstock or stock solution or suspension. The atomised solution or suspension is then directed into a drying chamber of the spray drying apparatus. Warmed gases are passed through the drying chamber to evaporate the solvent and form dry particles. The formed particles are separated from the moist gas stream and collected. The powder formulation of the ^rst aspect of the invention is preferably in the form of a solid particulate powder. The solid particulate powder may be a solid microparticulate powder. The solid particulate powder may have a D10 above 1 µm, especially above 10 µm. The solid particulate powder may have a D90 below 500 µm. The solid particulate powder may have a D50 in a range of 1-500 µm. It will be understood that, as is usual in particle size measurement, the term ^D50^ may refer to the particle size corresponding to a cumulative frequency of 50 % as determined by a cumulative particle size distribution. Similarly, ^D10^ may refer to the particle size corresponding to a cumulative frequency of 10 %. ^D90^ may refer to the particle size corresponding to a cumulative frequency of 90 %. These may be measured by laserdi raction.The solid particulate powder may have a D50 above 10 µm, especially above 20 µm. The solid particulate powder may have a D50 of no more than 200 µm. The D50 may for example be in the range of 20-50 µm, such as 25-30 µm. Advantageously, no more than 10 % v / v of the particles of the solid particulate powder have a diameter of less than 10 µm; and / or no more than 10 % v / v of the particles of the solid particulate powder have a diameter of more than 500 µm. Preferably, the solid particulate powder has a D50 of at least 20 µm (such as a D50 of 20 µm to 200 µm) and no more than 10 % v / v of the particles of the solid particulate powder have a diameter of less than 10 µm. Such features may be especially suitable when the use is nasal delivery. The solid particulate powder may have a D50 in a range of 1-5 µm, especially when the use is delivery by inhalation. Particle size measurements may be expressed by a volume-based percentile measurement, or cumulative volume. ^Dv10^ refers to a particle size that 10% of the particles by volume are smaller than. Thus, a Dv10 of 10 µm means that 10% of the total particle volume consists of particles smaller than 10 µm. ^Dv50^ refers to a volume- based median diameter, i.e. particle size that 50% of the particles by volume are smaller than. ^Dv90^ refers to a particle size that 90% of the total particles by volume are smallerthan. The particle size may be measured by laser di raction.The solid particulate powder may be a solid microparticulate powder. The solid particulate powder may have a Dv10 above 1 µm, especially above 10 µm. The solid particulate powder may have a Dv10 below 20 µm, especially below 15 µm. The solid particulate powder may have a Dv10 in the range of 1-20 µm, especially 10-15 µm. The solid particulate powder may have a Dv90 below 500 µm, especially below 100 µm. The solid particulate powder may have a Dv90 above 30 µm. The solid particulate powder may have a Dv90 in the range of 30-500 µm, especially 50-100 µm. The solid particulate powder may have a Dv50 in a range of 1-500 µm. The solid particulate powder may have a Dv50 above 10 µm, especially above 20 µm. The solid particulate powder may have a Dv50 of no more than 200 µm. The Dv50 may for example be in the range of 20-50 µm, such as 25-30 µm, especially 15-30 µm. Advantageously, no more than 10 % v / v of the particles of the solid particulate powder have a diameter of less than 10 µm; and / or no more than 10 % v / v of the particles of the solid particulate powder have a diameter of more than 500 µm. Preferably, the solid particulate powder has a Dv50 of at least 20 µm (such as a Dv50 of 20 µm to 200 µm) and no more than 10 % v / v of the particles of the solid particulate powder have a diameter of less than 10 µm. Such features may be especially suitable when the use is nasal delivery. The solid particulate powder may have a Dv50 in a range of 1-5 µm, especially when the use is delivery by inhalation. Preferably, the powder formulation is stable and degradation of the GLP-1 agonist, especially semaglutide is minimised, especially at elevated temperatures. ModulatedDi erential Scanning Calorimetry (mDSC)may be used to determine glass transitiontemperature using any suitable DSC device. Viscosity modi^ers are con^gured to change the thickness or texture of pharmaceutical ingredients. Viscosity modi^ers can include such products as thickeners, texturizers, gelation agentsand sti ening agents.Suitable polymeric viscosity modi^ers include polysaccharides, including cellulose derivatives and glycosaminoglycans. Suitable cellulose derivatives include cellulose ether derivatives, for example methyl cellulose, ethyl cellulose, hydroxyl ethyl cellulose, carboxy methyl cellulose and hydroxypropyl methylcellulose; and cellulose ester derivatives such as cellulose acetate, cellulose acetate phthalate, cellulose acetate butyrate, cellulose acetate propionate and hydroxypropyl methylcellulose phthalate. Suitable glycosaminoglycans include hyaluronic acid and derivatives thereof. Preferred polymeric viscosity modi^ers are cellulose ether derivatives, especially hydroxypropyl methylcellulose (HPMC) which has the international non-proprietary name (INN) ^hypromellose^. The polymeric viscosity modi^er may typically have a Mw (weight average molecular weight) as measured by gel permeability chromatography (GPC) of from 20 to 1000 kDa, especially from 50 to 200 kDa. The polymeric viscosity modi^er may be a polysaccharide, including cellulose derivatives and glycosaminoglycans, having a Mw (of from 20 to 1000 kDa, especially from 50 to 200 kDa. The polymeric viscosity modi^er may typically have a viscosity as a 2% (w / w) solution in water at 20 °C of from 1.5 to 20 mPas, such as from 2 to10 mPas. For avoidance of doubt, the term ^viscosity^ as used herein refers to dynamic viscosity, e.g. as measured by a rotational viscometer. The polymeric viscosity modi^er may be a polysaccharide, including cellulose derivatives and glycosaminoglycans, having a viscosity as a 2% (w / w) solution in water at 20 °C of from 1.5 to 20 mPas, such as from 2 to10 mPas.Hydroxypropyl methylcellulose (HPMC) has been found to be a particularly e ectivepolymeric viscosity modi^er for use in combination with the other excipients described herein and / or with a GLP-1 receptor agonist (especially semaglutide). Hydroxypropyl methylcellulose (HPMC) has been found to be advantageous in enhancing the solubility of some permeability enhancers, especially salt of fatty acids having a chain length of from 6 to 22-carbon atoms optionally substituted an aromatic group, such as sodium salcaprozate (SNAC). Thus, the formulations, feedstocks and dosage forms described herein may especially comprise: -a combination of HPMC and the GLP-1 receptor agonist (especially semaglutide);or -combinations of HPMC, SNAC and the GLP-1 receptor agonist (especiallysemaglutide). Liquid formulations, liquid feedstocks and dosage forms comprising a combination of HPMC and SNAC, combinations of HPMC and semaglutide and combinations of HPMC, SNAC and semaglutide may be present in some preferred embodiments.Hydroxypropyl methylcellulose (HPMC) comes in various grades having di eringviscosities and weight average molecular weights. Preferred grades have the weight average molecular weight and / or viscosity characteristics described above. HMPC-603 having a viscosity as a 2% (w / w) solution in water at 20 °C of 3 mPas and HMPC-606 having a viscosity as a 2% (w / w) solution in water at 20 °C of 6 mPas have been found to be particularly suitable for use in the formulations of the invention. The inclusion of a polymeric viscosity modi^er has been found to increase residence, improve spray performance (such as when the powder is prepared as a spray dried powder) and / or improve powder processing. The inclusion of a polymeric viscosity modi^er, especially HPMC, may improve particle size distribution, in particular by decreasing the percentage of particles (v / v) having a diameter of less than 10 µm. The inclusion of said polymer viscosity modi^er may improve long-term particle size stability. The polymeric viscosity modi^er may be present in an amount of 2-75 % w / w, such as 2- 45 % w / w or 45 to 75 % w / w, especially 45 to 75 % w / w, based on the total weight of the following, taken together: the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and (if present) the optional amino acid component. (I.e., this is based on the weight of the excipient package as that term is used herein; since, taken together, these components may be referred to as an excipient package. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist, or any other components which may be present in the powder formulation.) Optionally, the polymeric viscosity modi^er may be present in no more than 75 % w / w based on the total weight of the excipient package. Optionally, the polymeric viscosity modi^er may be present in at least 45 % w / w based on the total weight of the excipient package. Bulking agents are ^ller excipients used to increase the volume of a powder to enable easier processing thereof and / or to make the powder up to a volume suitable for consumption. Moreover, a bulking agent can stabilize the powder and promote ease of manufacturing. Suitable bulking agents for the powder formulation, liquid formulation and dosage forms of the present invention include sugar alcohols such as mannitol, sorbitol and erthritol, especially mannitol. Additionally or alternatively, the bulking agent may comprise or consist of one or more cyclodextrins. Thus, one or more cyclodextrins, such as those having 5 to 10 glucose units, such as -cyclodextrin (IUPAC name: cyclomaltoheptaose, also known as^Betadex^) and 2-hydroxypropyl- -cyclodextrin (also known as ^HP-Betadex^) may beincluded in the liquid and powder formulations, feedstocks and dosage forms of the invention as a bulking agent. As discussed in more detail below, cyclodextrins may also function as a permeability enhancer. Thus, one or more cyclodextrins may be present as a bulking agent, as a permeability enhancer or as both a bulking agent and a permeability enhancer. The bulking agent may be present in an amount of 5-75 % w / w, such as 5-45 % w / w or 45 to 75 % w / w, based on the total weight of the following, taken together: (if present) the polymeric viscosity modi^er; the bulking agent; the permeability enhancer; and (if present) the optional amino acid component. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist, or any other components, such as binder, which may be present in the powder formulation.) Where the formulation comprises cyclodextrin, the total content of cyclodextrin in the excipient package (whether cyclodextrin is described as a bulking agent or permeation enhancer) may be as described for the bulking agent above. The polymeric viscosity modi^er and the bulking agent, in combination, may be present in an amount of 5-75 % w / w, such as 5-45 % w / w or 45 to 75 % w / w, based on the total weight of the following, taken together: (if present) the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and (if present) the optional amino acid component. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist, or any other components, such as binder, which may be present in the powder formulation.) When the formulation is a liquid formulation, the polymeric viscosity modi^er and the bulking agent may optionally together constitute from 20 to 70 % w / w w / w of the excipient package, such as from 30 to 60 % w / w w / w of the excipient package. The amino acidThe amino acid component may be or comprise one or more di erent amino acids.Suitable amino acids include -amino acids with non-polar, aliphatic side groups, such as glycine, alanine, leucine, valine and isoleucine. Preferred amino acids include leucine, valine and isoleucine, especially leucine, most especially L-leucine. Amino acids have been found to be useful in stabilising a GLP-1 receptor agonist (especially semaglutide). Furthermore, an amino acid component may be present as a hydrophobic agent to assisting in coating particles of dry powder formulations. Without wishing to be bound by theory, it has also been found that an amino acid, especially leucine, may help to coat the GLP-1 receptor agonist (especially semaglutide), thereby protecting it from moisture. When the powder comprises a cyclodextrin (which may be hydrophilic) the presence of an amino acid such as leucine may be especially advantageous. Amino acids have been found to be useful in stabilising peptides, especially in solution. When the formulation is a liquid formulation, the optional amino acid component may constitute from 0 to 20 % w / w w / w of the excipient package, such as from 5 to 15% w / w w / w of the excipient package. When the formulation is a powder formulation, the amino acid, if present, may be present in an amount of 2-15 % w / w, such as 5-15 % w / w, especially 8-12 % w / w, based on the total weight of the following, taken together: (if present) the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and the amino acid component. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist, or any other components, such as binder, which may be present in the powder formulation.) Permeability enhancers are used to increase the bioavailability of a GLP-1 receptor agonist (especially semaglutide). In the present art, the terms ^permeation enhancer^ and ^permeability enhancer^ may be used interchangeably. Permeability enhancers are known to assist in the absorption of semaglutide via a transcellular route. For example, semaglutide in a tablet co-formulated with the absorption enhancer sodium N-[8-(2-hydroxylbenzoyl) amino] caprylate (SNAC-8), has been formulated for the treatment of type 2 diabetes (see: Davies et al., ^E Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes^, JAMA, 2017; 318(15): 1460^1470). The permeability enhancer present in the formulations of the invention may be a single compound or a combination of more than one permeability enhancer compounds. Preferred permeability enhancers include: -cyclodextrins, e.g. with 5 to 10 glucose units, such as -cyclodextrin (IUPAC name:cyclomaltoheptaose, also known as ^Betadex^) and 2-hydroxypropyl- -cyclodextrin (also known as ^HP-Betadex^); -phosphocholines such as dodecylphosphocholine (DPC);- fatty acid esters of carnitine, such as lauroyl-L-carnitine (LLC);- salts of a fatty acid having a chain length of from 6 to 22-carbon atoms optionallysubstituted an aromatic group, such as sodium salcaprozate (SNAC) (IUPAC name: N-[8(2-hydroxylbenzoyl) amino] caprylate) or sodium caprate; and -medium-chain fatty acid esters, with 6 to14 carbon atoms in the fatty acidportion. Other suitable permeability enhancers may include N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC), 1 phenylpiperazine (PPZ) and sodium deoxycholate(SDC). The permeability enhancer is optionally selected from one or more of a cyclodextrin, a phosphocholine, a fatty acid ester of carnitine, a salt of a fatty acid having a chain length of from 6 to 22-carbon atoms optionally substituted with an aromatic group, and a medium-chain fatty acid ester having a chain length of from 6 to 22-carbon atoms in the fatty acid portion. Preferably, the permeability enhancer is DPC or -cyclodextrin or mixtures thereof. It is believed that solid powder formulations comprising GLP-1, particularly semaglutide, have improved particle size distribution and long-term stability when the permeability enhancer is DPC or -cyclodextrin or mixtures thereof. Optionally, the formulation, especially the dry powder formulation, may comprise no more than 5 % w / w fatty acid esters of carnitine, especially lauroyl-L-carnitine (LLC), not more than 1 % w / w LLC, or preferably the formulation may not contain LLC. It has been discovered that LLC results in greater than 10% v / v of particles having a particle size of less than 10 µm and additionally, that LLC is detrimental to long-term stability of dry powder formulations. The permeability enhancer may be present in an amount of 5-85 % w / w, such as 5-30 % w / w, 30-50 % w / w, 50-75 % w / w, or 75-85 % w / w, based on the total weight of the following, taken together: (if present) the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and (if present) the amino acid component. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist, or any other components, such as binder, which may be present in the powder formulation.). Preferably, the excipient package comprises no more than 60% w / w of permeation enhancer, preferably no more than 40% w / w of permeation enhancer. Preferably, the excipient package comprises at least 20 % w / w of permeation enhancer. Preferably, the permeability enhancer is present in an amount of 20-60 % w / w, especially 20-40 % w / w, based on the total weight of the excipient package. In formulations of the invention, the permeability enhancer is optionally selected from one or more of: a cyclodextrin; a phosphocholine; a fatty acid ester of carnitine; and a salt of a fatty acid having a chain length of from 6 to 22-carbon atoms optionally substituted with an aromatic group.Cyclodextrins such as -cyclodextrin and 2-hydroxypropyl- -cyclodextrin can forminclusion complexes with a GLP-1 receptor agonist (especially semaglutide), improving the solubility and stability of the GLP-1 receptor agonist in aqueous environments. By enhancing solubility, they facilitate better absorption across biological membranes and protect the GLP-1 receptor agonist from enzymatic degradation. Preferred cyclodextrins include 5 to 10 glucose units. When the permeability enhancer consists of or comprises one or more cyclodextrins, the permeability enhancer may be present in an amount of 5-85 % w / w, such as 5-30 % w / w, 30-50 % w / w, 50-75 % w / w, or 75-85 % w / w, based on the total weight of the following, taken together: (if present) the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and (if present) the amino acid component. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist, or any other components, such as binder, which may be present in the powder formulation.) When the permeation enhancer comprises cyclodextrin, the total content of cyclodextrin optionally does not exceed the amounts disclosed above in relation to the bulking agent. In formulations of the invention, phosphocholines (which may be considered phospholipids) can function to disrupt lipid bilayers and enhance membrane permeability. The disruption of lipid structure allows the GLP-1 receptor agonist to pass through more easily thereby enhancing the transport of the GLP-1 receptor agonist through membrane barriers. Phosphocholines include lysophosphatidylcholines having one fatty acid chain on a glycerol group attached to phosphate, phosphatidylcholines having two fatty acid chains on a glycerol group attached to phosphate and alkylated phosphocholine having an alkyl chain directly attached to the phosphate of the phosphocholine head group. The alkyl or fatty acid chain length is typically of from 6 to 22-carbon atoms and may be saturated or unsaturated, for example with one or two C=C unsaturated groups. Examples of phosphocholine permeability enhancers include dodecylphosphocholine (DPC) having a saturated 12-carbon alkyl chain, hexadecylphosphocholine (miltefosine) having a saturated 16-carbon alkyl chain attached to a phosphocholine head group, oleylphosphocholine (OlPC) having an unsaturated 18-carbon oleyl chain linked to a phosphocholine head group, and octadecylphosphocholine having an 18-carbon saturated alkyl chain attached to a phosphocholine head group. When the permeability enhancer consists of or comprises one or more phosphocholines, the permeability enhancer may be present in an amount of 2-30 % w / w, such as 2-15 % w / w or 15-30 % w / w, based on the total weight of the following, taken together: (if present) the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and (if present) the amino acid component. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist, or any other components, such as binder, which may be present in the powder formulation.) When the permeability enhancer consists of or comprises one or more phosphocholines, the permeability enhancer may be present in an amount of 20-60 % w / w, based on the total weight of the following, taken together: (if present) the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and (if present) the amino acid component. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist, or any other components, such as binder, which may be present in the powder formulation.) In formulations of the invention, fatty acid esters of carnitine, where carnitine is conjugated with fatty acids of varying chain lengths, e.g. with a fatty acid chain length of 6 to 22-carbon atoms, can enhance membrane ^uidity and transport mechanisms dueto their amphiphilic nature. They may facilitate passive di usion and active transport ofthe GLP-1 receptor agonist across cellular membranes, increasing the absorption of the GLP-1 receptor agonist. The mechanism of action is similar across these esters, as they tend to interact with the lipid bilayer of biological membranes, enhancing permeability by altering the membrane structure. The permeability enhancer may thus include one or more of the following fatty acid esters of carnitine: caproyl-L-carnitine (CLC) having a C6 chain; lauroyl-L-carnitine (LLC) having a C12 chain; myristoyl-L-carnitine (MLC) having a C14 chain; palmitoyl-L-carnitine (PLC) having a C16 chain; and stearoyl-L-carnitine (SLC) having a C18 chain. A preferred fatty acid ester of carnitine is lauroyl-L-carnitine (LLC). When the permeability enhancer consists of or comprises one or more fatty acid ester of carnitines, the permeability enhancer may be present in an amount of 2-30 % w / w, such as 2-15 % w / w or 15-30 % w / w, based on the total weight of the following, taken together: (if present) the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and (if present) the amino acid component. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist, or any other components, such as binder, which may be present in the powder formulation.) In formulations of the invention, salts of fatty acids may act as permeability enhancers by increasing the solubility of and / or stabilizing the GLP-1 receptor agonist (especially semaglutide) in the gastrointestinal tract; while also enhancing permeability. Suitable salts of fatty acids typically include a fatty acid chain of from 6 to 22-carbon atoms, optionally substituted with an aromatic group such as a benzoyl group, e.g. a (hydroxybenzoyl)amino group. They may act as carriers that help in the transport of the GLP-1 receptor agonist (especially semaglutide) across the intestinal barrier, thereby improving their systemic availability. The permeability enhancer may include one or more of the following unsubstituted fatty acid salt molecules: sodium caprylate, the sodium salt of caprylic acid (C8); sodium caprate, the sodium salt of capric acid (C10); and sodium laurate, the sodium salt of lauric acid (C12). The permeability enhancer may include one or both of the following substituted fatty acid salt permeability enhancers: sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC-8); and sodium N-[8-(2-hydroxybenzoyl)amino]caproate (SNAC, or sodium salcaprozate), both of which include the (hydroxybenzoyl)amino substituent on the fatty acid chain. When the permeability enhancer consists of or comprises one or more salt of fatty acid permeability enhancers, the permeability enhancer may be present in an amount of 5-85 % w / w, such as 15-35% w / w, 20-30 % w / w, 40-60 % w / w, or 60-80 % w / w, based on the total weight of the following, taken together: (if present) the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and (if present) the amino acid component. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist, or any other components, such as binder, which may be present in the powder formulation.) Another class of permeability enhancers are medium-chain fatty acid ester having a chain length of from 6 to 22-carbon atoms in the fatty acid portion, such as from 6 to 14 carbon atoms in the fatty acid portion. Medium-chain fatty acid esters, with 6 to14 carbon atoms in the fatty acid portion, can improve mucosal permeability and are often used in formulations for nasal delivery. An example of a suitable medium-chain fatty acid ester permeability enhancer is a lauric acid (C12) ester such as glycerol monolaurate and glycerol dilaureate and a caprylic acid (C10) ester such as glycerol monocaprylate and caprylic acid triglycerides. In preferred embodiments, the permeability enhancer consists of or comprises one or more of: --cyclodextrin (^Betadex^),- 2-hydroxypropyl- -cyclodextrin (^HP-Betadex^),- dodecylphosphocholine (DPC),- lauroyl-L-carnitine (LLC); and- sodium salcaprozate (SNAC).The permeability enhancer may be one of, a combination of two of, or a combination of three of: --cyclodextrin (^Betadex^),- 2-hydroxypropyl- -cyclodextrin (^HP-Betadex^),- dodecylphosphocholine (DPC),- lauroyl-L-carnitine (LLC); and- sodium salcaprozate (SNAC).Preferred permeability enhancers are dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC) and sodium salcaprozate (SNAC). In especially preferred embodiments, the permeability enhancer consists of or comprises one or more of: -dodecylphosphocholine (DPC);- lauroyl-L-carnitine (LLC); and- sodium salcaprozate (SNAC).In such embodiments, the permeability enhancer may be or comprise both lauroyl-L- carnitine (LLC) and sodium salcaprozate (SNAC). Especially, the permeability enhancer may be or comprise sodium salcaprozate (SNAC). The permeability enhancer may, for example, be one of: dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC) and sodium salcaprozate (SNAC); a combination of two of dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC) and sodium salcaprozate (SNAC); or a combination of all three of dodecylphosphocholine (DPC), lauroyl-L- carnitine (LLC) and sodium salcaprozate (SNAC). Optionally, formulations disclosed herein comprise less than about 0.1 % w / w LLC, most preferably do not comprise LLC. The most preferred permeability enhancer is sodium salcaprozate (SNAC). When selected as a permeability enhancer of a liquid formulation, sodium salcaprozate (SNAC) may be present in a concentration in the liquid formulation of 10 mg / mL or less, preferably 6 mg / L or less. Advantageously, when SNAC is provided in a concentration of 10 mg / mL or less, the excipient package comprises HPMC as at least one of the viscosity modi^ers of the excipient package. Preferably, when SNAC is provided in a concentration of 10 mg / mL or less in the formulation, HPMC is provided in a concentration of at least 10mg / mL such as at least 15 mg / mL. The permeability enhancer may constitute from 10 to 75 % w / w of the excipient package, such as from 25 to 65 % w / w of the excipient package. Optionally, formulations disclosed herein comprise a permeation enhancer and GLP-1, especially semaglutide in a weight ratio of about 1:1, 2:1, 3:1, and any ratio in between, preferably in the ratio of about 3:1. Without wishing to be bound by theory, it is believed that increasing the ratio of permeation enhancer to semaglutide, decreases viscosity of the feedstock solution and / or improves particle size distribution. Where more than one type of permeation enhancer is present, the total weight of the permeation enhancers may be within the weight ratio described. Optionally, formulations disclosed herein comprise a polymeric viscosity modi^er, especially HPMC, and a permeation enhancer in a weight ratio of about 3:1, 2:1 or 1:1 and any ratio in between. Without wishing to be bound by theory, it is believed that an excess of polymeric viscosity modi^er increases particle size. The powder formulation may comprise or consist of the following components: -a viscosity modi^er (especially one or more cellulose ether derivatives, such ashydroxypropyl methylcellulose (HPMC)) in a range of 15-75 % w / w; -a bulking agent (especially one or more sugar alcohols, such as mannitol) in arange of 15-75 % w / w; and -an optional amino acid (especially one or more -amino acids with non-polar,aliphatic side groups, such as leucine) which, when present, is present in a range of 5-15 % w / w, wherein the % w / w values are based on the combined weight of: the viscosity modi^er; the bulking agent; and (if present) the amino acid. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist (such as semaglutide), or any other components, such as binder, which may be present in the powder formulation.) Optionally, the combined % w / w of the viscosity modi^er and the bulking agent is in a range of 85-95 % w / w. The powder formulation may comprise or consist of the following components: -a viscosity modi^er (especially one or more cellulose ether derivatives, such ashydroxypropyl methylcellulose (HPMC)) in a range of 15-65 % w / w (such as in a range of 15-25 % w / w or in a range of 55-65 % w / w); -an optional bulking agent (especially one or more sugar alcohols, such asmannitol) which, when present, is present in a range of 15-65 % w / w (such as in a range of 15-25 % w / w or in a range of 55-65 % w / w); -an optional amino acid (especially one or more -amino acids with non-polar,aliphatic side groups, such as leucine) which, when present, is present in a range of 5-15 % w / w; and -a permeability enhancer (especially one or more cyclodextrins, such as -cyclodextrin i.e. "betadex" and / or hydroxypropyl- -cyclodextrin i.e. "HP-betadex")in a range of 5-85 % w / w (such as in a range of 5-35 % w / w or in a range of 75-85 % w / w), wherein the % w / w values are based on the total weight of: the viscosity modi^er; (if present) the bulking agent; (if present) the amino acid; and the permeability enhancer. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist (such as semaglutide), or any other components, such as binder, which may be present in the powder formulation.) Optionally, the combined % w / w of the viscosity modi^er and the bulking agent is in a range of 15-85 % w / w. The powder formulation may comprise or consist of the following components: -a viscosity modi^er (especially one or more cellulose ether derivatives, such ashydroxypropyl methylcellulose (HPMC)) in a range of 5-65 % w / w (such as in a range of 5-15 % w / w, a range of 30-50 % w / w, or a range of 55-65 % w / w); -a bulking agent (especially one or more sugar alcohols, such as mannitol) in arange of 5-65% w / w (such as in a range of 5-15 % w / w, a range of 30-50 % w / w, or a range of 55-65 % w / w); -an amino acid (especially one or more -amino acids with non-polar, aliphaticside groups, such as leucine) in a range of 5-15 % w / w; -an optional ^rst permeability enhancer (especially one or more cyclodextrins,such as -cyclodextrin i.e. "betadex" and / or hydroxypropyl- -cyclodextrin i.e. "HP-betadex") which, when present, is present in a range of 5-15 % w / w; and -a second (i.e., di erent) permeability enhancer (especially one or morephosphocholines, such dodecylphosphocholine i.e. DPC) in a range of 5-15 % w / w, wherein the % w / w values are based on the total weight of: the viscosity modi^er; the bulking agent; the amino acid; (if present) the ^rst permeability enhancer; and the second permeability enhancer. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist (such as semaglutide), or any other components, such as binder, which may be present in the powder formulation.) Optionally, the combined % w / w of the viscosity modi^er and the bulking agent is in a range of 45-85 % w / w. The powder formulation may comprise or consist of the following components: -a viscosity modi^er (especially one or more cellulose ether derivatives, such ashydroxypropyl methylcellulose (HPMC)) in a range of 15-65 % w / w (such as in a range of 15-25 % w / w or in a range of 40-65 % w / w); -an optional bulking agent (especially one or more sugar alcohols, such asmannitol) which, when present, is present in a range of 30-45% w / w; -an optional amino acid (especially one or more -amino acids with non-polar,aliphatic side groups, such as leucine) which, when present, is present in a range of 5-15 % w / w (such as in a range of 15-25 % w / w or in a range of 65-75 % w / w); -an optional ^rst permeability enhancer (especially one or more cyclodextrins,such as -cyclodextrin i.e. "betadex" and / or hydroxypropyl- -cyclodextrin i.e. "HP-betadex") which, when present, is present in a range of 15-75 % w / w (such as in a range of 15-25 % w / w or in a range of 65-75 % w / w); and -a second permeability enhancer (especially one or more phosphocholines, suchdodecylphosphocholine i.e. DPC) in a range of 5-25 % w / w, wherein the % w / w values are based on the total weight of: the viscosity modi^er; (if present) the bulking agent; (if present) the amino acid; (if present) the ^rst permeability enhancer; and the second permeability enhancer. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist (such as semaglutide), or any other components, such as binder, which may be present in the powder formulation.) Optionally, the combined % w / w of the viscosity modi^er and the bulking agent is in a range of 45-95 % w / w. The powder formulation may comprise or consist of the following components: -a viscosity modi^er (especially one or more cellulose ether derivatives, such ashydroxypropyl methylcellulose (HPMC)) in a range of 5-65 % w / w (such as in a range of 5-15 % w / w, a range of 30-50 % w / w, or a range of 55-65 % w / w);- a bulking agent (especially one or more sugar alcohols, such as mannitol) in arange of 5-65% w / w (such as in a range of 5-15 % w / w, a range of 30-50 % w / w, or a range of 55-65 % w / w); -an amino acid (especially one or more -amino acids with non-polar, aliphaticside groups, such as leucine) in a range of 5-15 % w / w; -an optional ^rst permeability enhancer (especially one or more cyclodextrins,such as -cyclodextrin i.e. "betadex" and / or hydroxypropyl- -cyclodextrin i.e. "HP-betadex") which, when present, is present in a range of 5-15 % w / w; and -a second permeability enhancer (especially one or more fatty acid esters ofcarnitine, such as lauroyl-L-carnitine, i.e. LLC) in a range of 5-15 % w / w, wherein the % w / w values are based on the total weight of: the viscosity modi^er; the bulking agent; the amino acid; (if present) the ^rst permeability enhancer; and the second permeability enhancer. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist (such as semaglutide), or any other components, such as binder, which may be present in the powder formulation.) Optionally, the combined % w / w of the viscosity modi^er and the bulking agent is in a range of 45-85 % w / w. The powder formulation may comprise or consist of the following components: -a viscosity modi^er (especially one or more cellulose ether derivatives, such ashydroxypropyl methylcellulose (HPMC)) in a range of 15-65 % w / w (such as in a range of 15-25 % w / w or a range of 40-65 % w / w); -an optional bulking agent (especially one or more sugar alcohols, such asmannitol) which, when present, is present in a range of 30-45 % w / w; -an optional amino acid (especially one or more -amino acids with non-polar,aliphatic side groups, such as leucine) which, when present, is present in a range of 5-15 % w / w; -an optional ^rst permeability enhancer (especially one or more cyclodextrins,such as -cyclodextrin i.e. "betadex" and / or hydroxypropyl- -cyclodextrin i.e. "HP-betadex") which, when present, is present in a range of 15-75 % w / w (such as in a range of 15-25 % w / w or a range of 55-75 % w / w); and -a second permeability enhancer (especially one or more fatty acid esters ofcarnitine, such as lauroyl-L-carnitine, i.e. LLC) in a range of 5-25 % w / w, wherein the % w / w values are based on the total weight of: the viscosity modi^er; (if present) the bulking agent; (if present) the amino acid; (if present) the ^rst permeability enhancer; and the second permeability enhancer. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist (such as semaglutide), or any other components, such as binder, which may be present in the powder formulation.) Optionally, the combined % w / w of the viscosity modi^er and the bulking agent is in a range of 15-95 % w / w. The powder formulation may comprise or consist of the following components: -a viscosity modi^er (especially one or more cellulose ether derivatives, such ashydroxypropyl methylcellulose (HPMC)) in a range of 5-40 % w / w; -a bulking agent (especially one or more sugar alcohols, such as mannitol) in arange of 2-35 % w / w; -an amino acid (especially one or more -amino acids with non-polar, aliphaticside groups, such as leucine) in a range of 5-15 % w / w; and -a permeability enhancer (especially a salt of a fatty acid having a chain length offrom 6 to 22-carbon atoms optionally substituted an aromatic group, such as sodium salcaprozate i.e. SNAC) in a range of 45-55 % w / w, wherein the % w / w values are based on the total weight of: the viscosity modi^er; the bulking agent; the amino acid; and the permeability enhancer. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist (such as semaglutide), or any other components, such as binder, which may be present in the powder formulation.) Optionally, the combined % w / w of the viscosity modi^er and the bulking agent is in a range of 45-75 % w / w. The powder formulation may comprise or consist of the following components: -an optional viscosity modi^er (especially one or more cellulose ether derivatives,such as hydroxypropyl methylcellulose (HPMC)) which, when present, is present in a range of 5-35 % w / w; -an optional bulking agent (especially one or more sugar alcohols, such asmannitol) which, when present, is present in a range of 5-35 % w / w; -an optional amino acid (especially one or more -amino acids with non-polar,aliphatic side groups, such as leucine) which, when present, is present in a range of 5-15 % w / w; and -an optional ^rst permeability enhancer (especially one or more cyclodextrins,such as -cyclodextrin i.e. "betadex" and / or hydroxypropyl- -cyclodextrin i.e. "HP-betadex") which, when present, is present in a range of 5-15 % w / w; and -a second permeability enhancer (especially a salt of a fatty acid having a chainlength of from 6 to 22-carbon atoms optionally substituted an aromatic group, such as sodium salcaprozate i.e. SNAC) in a range of 10-55 % w / w, wherein the % w / w values are based on the total weight of: (if present) the viscosity modi^er; (if present) the bulking agent; (if present) the amino acid; (if present) the ^rst permeability enhancer; and the second permeability enhancer. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist (such as semaglutide), or any other components, such as binder, which may be present in the powder formulation.) Optionally, the combined % w / w of the viscosity modi^er and the bulking agent is in a range of 30-55 % w / w. The powder formulation may comprise or consist of the following components: -a viscosity modi^er (especially one or more cellulose ether derivatives, such ashydroxypropyl methylcellulose (HPMC)) in a range of 20-40 % w / w; -a bulking agent (especially one or more sugar alcohols, such as mannitol) in arange of 20-40 % w / w; -an amino acid (especially one or more -amino acids with non-polar, aliphaticside groups, such as leucine) in a range of 5-15 % w / w; -an optional ^rst permeability enhancer (especially one or more cyclodextrins,such as -cyclodextrin i.e. "betadex" and / or hydroxypropyl- -cyclodextrin i.e. "HP-betadex") which, when present, is present in a range of 5-25 % w / w; -an optional second permeability enhancer (especially one or morephosphocholines, such dodecylphosphocholine i.e. DPC) which, when present, is present in a range of 2-15 % w / w; -an optional third permeability enhancer ((especially one or more fatty acid estersof carnitine, such as lauroyl-L-carnitine, i.e. LLC) which, when present, is present in a range of 2-15% w / w; -an optional fourth permeability enhancer (especially a salt of a fatty acid having achain length of from 6 to 22-carbon atoms optionally substituted an aromatic group, such as sodium salcaprozate i.e. SNAC) which, when present, is present in a range of 20-30 % w / w; wherein the % w / w values are based on the total weight of: the viscosity modi^er; the bulking agent; the amino acid; (if present) the ^rst permeability enhancer; (if present) the second permeability enhancer; (if present) the third permeability enhancer; and (if present) the fourth permeability enhancer. (I.e., this is based on the weight of the excipient package as that term is used herein. Thus, it will be appreciated, the % w / w values recited here do not factor in the weight of GLP-1 receptor agonist (such as semaglutide), or any other components, such as binder, which may be present in the powder formulation.) Optionally, the combined % w / w of the viscosity modi^er and the bulking agent is in a range of 40-75 % w / w. The excipient package of the liquid formation consists of (a) at least one of a polymeric viscosity modi^er and a bulking agent, (b) an optional amino acid component, (c) a permeability enhancer, and (d) an optional binder. The excipient package advantageously contains both a polymeric viscosity modi^er and a bulking agent. For the avoidance of doubt, the formulations, feedstocks and dosage forms of the invention include no polymeric viscosity modi^er, bulking agent, amino acid component, permeability enhancer or binder other than that included in the excipient package. The excipient package of the liquid formation typically consists of from 20 to 70 % w / w w / w of (a) at least one of a polymeric viscosity modi^er and a bulking agent, from 0 to 20 % w / w w / w of (b) the optional amino acid component, from 10 to 75 % w / w w / w of (c) the permeability enhancer, and from 0 to 10 % w / w w / w of (d) the optional binder. The excipient package may, for example, consist of from 30 to 60 % w / w w / w of (a) at least one of a polymeric viscosity modi^er and a bulking agent, from 5 to 15 % w / w w / w of (b) the amino acid component, and from 25 to 65 % w / w w / w of (c) the permeabilityenhancer. All the above amounts expressed in weight percentages are based on the totalweight of the excipient package. The excipient package of the liquid formation may consist of: (a) at least one of a polysaccharide viscosity modi^er and a sugar alcohol bulking agent, (b) an optional - amino acid with a non-polar, aliphatic side, (c) a permeability enhancer, and (d) an optional binder. The excipient package of the liquid formation may consist of: (a) both a polysaccharide viscosity modi^er and a sugar alcohol bulking agent, (b) an -amino acid with a non- polar, aliphatic side chain, (c) a permeability enhancer, and (d) an optional binder. The excipient package of the liquid formation may consist of: (a) at least one of a polymeric viscosity modi^er and bulking agent, (b) an optional amino acid component, and (c) a permeability enhancer selected from one or more of a cyclodextrin, dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), sodium salcaprozate (SNAC) and a medium-chain fatty acid esters, with 6 to14 carbon atoms in the fatty acid portion, and (d) an optional binder. The excipient package of the liquid formation may consist of: (a) both a polymeric viscosity modi^er and a bulking agent, (b) an optional amino acid, and (c) a permeability enhancer selected from one or more of a cyclodextrin, dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), sodium salcaprozate (SNAC) and a medium-chain fatty acid esters, with 6 to14 carbon atoms in the fatty acid portion, and (d) an optional binder. The excipient package of the liquid formation may consist of: (a) at least one of a polymeric viscosity modi^er and bulking agent, (b) an optional amino acid component, and (c) a permeability enhancer selected from one or more of -cyclodextrin, 2-hydroxypropyl- -cyclodextrin, dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC),and sodium salcaprozate (SNAC), and (d) an optional binder. The excipient package of the liquid formation may consist of: (a) both a polymeric viscosity modi^er and a bulking agent, (b) an optional amino acid component, and (c) apermeability enhancer selected from one or more of -cyclodextrin, 2-hydroxypropyl- -cyclodextrin dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), and sodium salcaprozate (SNAC), and (d) an optional binder. The excipient package of the liquid formation may consist of: (a) at least one of a polysaccharide viscosity modi^er and a sugar alcohol bulking agent, (b) an -amino acid with a non-polar, aliphatic side, and (c) a permeability enhancer selected from one or more of a cyclodextrin, dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), sodium salcaprozate (SNAC) and a medium-chain fatty acid esters, with 6 to14 carbon atoms in the fatty acid portion, and (d) an optional binder. The excipient package of the liquid formation may consist of: (a) both a polysaccharide viscosity modi^er and a sugar alcohol bulking agent, (b) an -amino acid with a non- polar, aliphatic side, and (c) a permeability enhancer selected from one or more of a cyclodextrin, dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), sodium salcaprozate (SNAC) and a medium-chain fatty acid esters, with 6 to14 carbon atoms in the fatty acid portion, and (d) an optional binder. The excipient package of the liquid formation may consist of: (a) at least one of a polysaccharide viscosity modi^er and a sugar alcohol bulking agent, (b) an -amino acid with a non-polar, aliphatic side, and (c) a permeability enhancer selected from one ormore of a -cyclodextrin, 2-hydroxypropyl- -cyclodextrin dodecylphosphocholine (DPC),lauroyl-L-carnitine (LLC), and sodium salcaprozate (SNAC), and (d) an optional binder. The excipient package of the liquid formation may consist of: (a) both a polysaccharide viscosity modi^er and a sugar alcohol bulking agent, (b) an -amino acid with a non- polar, aliphatic side, and (c) a permeability enhancer selected from one or more of a -cyclodextrin, 2-hydroxypropyl- -cyclodextrin dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), and sodium salcaprozate (SNAC), and (d) an optional binder. Powder formulations described herein may suitably be prepared by spray drying or freeze drying an aqueous solution of the components thereof. Preferably, the powder formulation is prepared by spray drying a liquid formulation, especially a liquid feedstock, described herein. Alternatively, the powder formulations may be prepared by combining solid constituents, for example, in a granulation process. As described, the GLP-1 receptor agonist (especially semaglutide) may be added (to a mixture of the at least one of a polymeric viscosity modi^er and a bulking agent; the permeability enhancer; and the optional amino acid component, i.e., to the excipient package as that term is used herein) prior to spray drying the mixture including the GLP-1 receptor agonist, to form a spray dried powder. The GLP-1 receptor agonist (especially semaglutide) may be added (to a mixture of the at least one of a polymeric viscosity modi^er and a bulking agent; the permeability enhancer; and the optional amino acid component, i.e., to the excipient package as that term is used herein) prior to freeze drying the mixture including the GLP-1 receptor agonist, to form a freeze dried powder. Alternatively, as described, the GLP-1 receptor agonist (especially semaglutide) may be added (subsequent to the spray drying) to a spray dried dry powder comprising or consisting of the at least one of a polymeric viscosity modi^er and a bulking agent; the permeability enhancer; and the optional amino acid component. The GLP-1 receptor agonist (especially semaglutide) may be added (subsequent to the freeze drying) to a freeze dried dry powder comprising or consisting of the at least one of a polymeric viscosity modi^er and a bulking agent; the permeability enhancer; and the optional amino acid component. The solution from which the formulations are spray dried or freeze dried may compriseone or more further components, such as a bu er, for example a phosphate butter;and / or one or more surfactants. Other components, such as a binder described herein, may be added before or after spray drying, or before or after freeze drying.The bu erA solution from which the powder formulations are spray dried or freeze dried (especially a liquid formulation or feedstock disclosed herein), or a powder formulation according to the present invention may preferably be maintained at a pH of between 6 and 8.5, especially between 6.7 and 7.7. A pH of between 6 and 8.5, especially between 6.7 and 7.7 may be particularly advantageous when the solution contains the GLP-1 receptoragonist, especially semaglutide. A bu ering agent may be included to maintain aconsistent acidity level. The formulation or dosage form of the invention may, for example, include (by virtue of itspreparation through spray drying) a bu ering agent suitable to maintain the pH of theformulation or dosage form between 6 and 8.5, especially between 6.7 and 7.7. Suitablebu ering agents include phosphate bu ers, acetate bu ers and the like. It has been found that the presence of surfactants is not required during spray drying to form the formulations and dosage forms of the invention. For example, it has been found that the presence of surfactants is not necessary to prevent the GLP-1 receptor agonist (especially semaglutide) and other constituents from adhering to equipment such as glassware, stainless steel and silicone tubing used in spray drying equipment. Thus, it has been found that the presence of surfactants is not required in the formulations and feedstocks of the invention. Formulations, feedstocks and dosage forms of the invention advantageously include essentially no surfactant, for example no more than 0.01 % w / w of surfactant, especially no more than 0.001 % w / w of surfactant, based on the total weight of the powder formulation or dosage form. The formulations, feedstocks and dosage forms of the invention advantageously include essentially no non-ionic surfactant, for example no more than 0.01 % w / w of non-ionic surfactant, especially no more than 0.001 % w / w of non-ionic surfactant, based on the total weight of the powder formulation or dosage form. The formulations and dosage forms of the invention advantageously include essentially no emulsi^er, for example no more than 0.01 % w / w of emulsi^er, especially no more than 0.001 % w / w of emulsi^er, based on the total weight of the powder formulation or dosage form. The formulations, feedstocks and dosage forms of the invention advantageously include essentially no polysorbate surfactant, for example no more than 0.01 % w / w of polysorbate surfactant, especially no more than 0.001 % w / w of polysorbate surfactant, based on the total weight of the powder formulation or dosage form. Preferably the formulations, feedstocks and dosage forms of the invention advantageously include essentially no surfactant selected from a polysorbate, sodium layyl sulphate, cremophor EL (Polyoxyl 35 Castor Oil) and oleic acid, for example no more than 0.01 % w / w of such surfactants, especially no more than 0.001 % w / w of such surfactants, based on the total weight of the powder formulation or dosage form. For the avoidance of doubt, permeability enhancers that have surfactant properties may be present in the powder formulation, liquid formulation or feedstock. Binders Optionally, the powder formulation liquid formulation, feedstock or dosage forms may comprise one or more binders. Binders may be present in the formulations, feedstocks and dosage forms described herein, for example to assist in forming and holding together particles in spray drying and other processes that form dry powders. The binder may include a water-activated polymeric binder, such as one or more of: povidone (polyvinylpyrrolidone), copovidone (a 3:2 copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate) and polyethylene glycol (PEG); especially, a polymeric binder which is an N-vinylpyrrolidone polymer or co- polymer, thus most especially povidone (polyvinylpyrrolidone). Optionally, when the formulation is a powder formulation or dosage form, the binder may be present in an amount in a range of 0.1-10 % w / w, such as 0.5-8 % w / w, such as 1-6 % w / w, based on the total weight of the powder formulation or dosage form. Optionally, when the formulation is a liquid formulation, feedstock or dosage form, the optional binder may constitute from 0.1 to 10 % w / w w / w of the excipient package, such as from 0.5 to 8 % w / w w / w of the excipient package, especially from 1 to 6 % w / w w / w of the excipient package. Optionally, no binder is present. The skilled person will be aware that some pharmaceutical excipients can have multiple functions. When a compound is present in the formulations of the present invention in order to perform a given function, then said compound is present in an amount speci^ed herein in relation to compounds having that function. For example, if a compound is present in the formulations of the present invention in order to function as a binder, then said compound is present in an amount of no more than 10 % w / w, based on the total weight of the powder formulation or dosage form, such as being present in a range of 0.1- 10 % w / w, such as 0.5-8 % w / w, such as 1-6 % w / w, such as 0.1-5 % w / w, such as 0.1-3 % w / w based on the total weight of the powder formulation or dosage form. However, if a compound that can function as a binder is present in the formulations of the present invention in order to perform a function other than as a binder that compound may be present in the amounts speci^ed herein for components having that alternative function. The liquid formulation or feedstock is typically an aqueous formulation comprising water as a carrier. Typically, at least 60 % w / w w / w of the liquid carrier is water with up to 40 % w / w w / w of the liquid carrier may be other solvents, such as C1-6 alcohol or alcohols. The liquid carrier may comprise from 60 to 100 % w / w w / w water and from 0 to 40 % w / w w / w ethanol, such as about 70 % w / w w / w water and about 30 % w / w w / w ethanol. In embodiments, at least 65 % % v / vof the liquid carrier is ethanol and no more than 35 % % v / v of the liquid carrier is water. The liquid formulation may be in the form of a solution or a suspension. In some embodiments, the powder formulation of the ^rst aspect of the invention may comprise:- a polymeric viscosity modi^er, especially a polysaccharide, most especially ahydroxypropyl methylcellulose (HMPC);- an optional bulking agent, especially a sugar alcohol and / or a cyclodextrin, mostespecially mannitol;- an optional amino acid component, especially an -amino acid with non-polar,aliphatic side groups, most especially leucine; and- a permeability enhancer, especially a permeability enhancer which consists of orcomprises one or more of dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), salcaprozate (SNAC),- the GLP-1 receptor agonist, especially semaglutide;the powder formulation optionally further comprising a binder. In such embodiments, the permeability enhancer may additionally or alternatively be or comprise one or more cyclodextrins, especially those having 5 to 10 glucose units, more especially -cyclodextrin (IUPAC name: cyclomaltoheptaose, also known as ^Betadex^)and / or 2-hydroxypropyl- -cyclodextrin (also known as ^HP-Betadex^).Thus, in the above embodiments, the permeability enhancer advantageously comprises or consists of one or more of the following: -cyclodextrins, especially those having 5 to 10 glucose units, more especially -cyclodextrin (IUPAC name: cyclomaltoheptaose, also known as ^Betadex^) and / or 2-hydroxypropyl- -cyclodextrin (also known as ^HP-Betadex^);- phosphocholines, especially dodecylphosphocholine (DPC);- fatty acid esters of carnitine, especially lauroyl-L-carnitine (LLC); and- a salt of a fatty acid having a chain length of from 6 to 22-carbon atoms optionallysubstituted with an aromatic group, especially sodium salcaprozate (SNAC) (IUPAC name: N-[8(2-hydroxylbenzoyl) amino] caprylate). Preferred liquid formulations In some embodiments, the liquid formulation of the third aspect of the invention may comprises: (i) a GLP-1 agonist, especially semaglutide,(ii) an excipient package consisting of: (a) a polymeric viscosity modi^er,especially a polysaccharide, and optionally a bulking agent, especially a sugar alcohol and / or a cyclodextrin, (b) an optional amino acid component, especially an -amino acids with non-polar, aliphatic side groups, (c) a permeability enhancer and (d) an optional binder; (iii) a liquid carrier;and optionally (iv) a bu er, for example a phosphate bu er. In some embodiments, the liquid formulation of the third aspect of the invention may comprises: (i) a GLP-1 agonist, especially semaglutide,(ii) an excipient package consisting of: (a) a cellulose polymeric viscositymodi^er, and one or more bulking agents, especially a sugar alcohol and / or a cyclodextrin, (b) an optional amino acid component, especially an -amino acids with non-polar, aliphatic side groups, (c) a permeability enhancer and (d) an optional binder; (iii) a liquid carrier;and optionally (iv) a bu er, for example, a phosphate bu er.In some embodiments, the liquid formulation of the third aspect of the invention may comprises: (i) a GLP-1 agonist, especially semaglutide,(ii) an excipient package consisting of: (a) a hydroxypropyl methyl celluloseviscosity modi^er, and one or more bulking agents selected from mannitol and cyclodextrins, (b) an optional -amino acids with non-polar, aliphatic side groups, (c) a permeability enhancer and (d) an optional binder; (iii) a liquid carrier;and optionally (iv) a bu er, for example, a phosphate bu er.In some embodiments, the liquid formulation of the third aspect of the invention may comprises: (i) a GLP-1 agonist, especially semaglutide,(ii) an excipient package consisting of: (a) a hydroxypropyl methyl celluloseviscosity modi^er, and one or more bulking agents selected from mannitol and cyclodextrins, (b) an -amino acids with non-polar, aliphatic side groups, (c) a permeability enhancer and (d) an optional binder; (iii) a liquid carrier;and optionally (iv) a bu er, for example, a phosphate bu er.In the above embodiments, the permeability enhancers is advantageously selected from: cyclodextrins, e.g. with 5 to 10 glucose units, such as -cyclodextrin (IUPAC name: cyclomaltoheptaose, also known as ^Betadex^) and 2-hydroxypropyl- -cyclodextrin; phosphocholines such dodecylphosphocholine (DPC); fatty acid esters of carnitine, such as lauroyl-L-carnitine (LLC); a salt of a fatty acid having a chain length of from 6 to 22-carbon atoms optionally substituted an aromatic group, such as sodium salcaprozate (SNAC) (IUPAC name: N-[8(2-hydroxylbenzoyl) amino] caprylate) or sodium caprate; and medium-chain fatty acid esters, with 6 to14 carbon atoms in the fatty acid portion. In the above embodiments, the permeability enhancers may be selected from: cyclodextrins, e.g. with 5 to 10 glucose units, such as -cyclodextrin (IUPAC name: cyclomaltoheptaose, also known as ^Betadex^) and 2-hydroxypropyl- -cyclodextrin; phosphocholines such dodecylphosphocholine (DPC); fatty acid esters of carnitine, such as lauroyl-L-carnitine (LLC); and a salt of a fatty acid having a chain length of from 6 to 22-carbon atoms optionally substituted an aromatic group, such as sodium salcaprozate (SNAC) (IUPAC name: N-[8(2-hydroxylbenzoyl) amino] caprylate) or sodium caprate. In the above embodiments, the permeability enhancers may be sodium salcaprozate (SNAC). The exemplary formulations described below were assessed against at least some of the quality target product pro^le criteria, requiring that the dry powder formulation is as follows : -well suited to collection (e.g. in terms of static charge, aggregation, ^owability,adhesion to vessel); -a low moisture (especially, low water) content (ideally less than 5% w / w; e.g.analysed by Karl Fischer colorimetry); -formed of appropriately sized particles;- good yield (when formed by spray drying from a solution in puri^ed water of thepowder components; ideally, the yield is more than 50%); and / or -an appropriate glass transition temperature (e.g. analysed by modulateddi erential scanning calorimetry, mDSC).A formulation preferably meets at least some, ideally all, of the above criteria. Thus, the quality target product pro^le for the dry powder formulations is listed in Table 1. Table 1: Quality target product pro^le Feature Target value Appearance Obtain powder that can feasibly be collected Moisture Content Less than 5 % w / w (based on total weight of powder Size For nasal delivery: no more than 10 % v / v of the particles have a diameter of less than 10 µm. For delivery by inhalation: the D50 of the particles is in a range of 1-5 µm. Yield More than 50 % (when spray dried from a solution of the components of the powder) The bulking agents, permeability enhancers and other excipients were obtained from the suppliers s shown in Table 2. Table 2: Materials Material Role SupplierMannitol Stabiliser / bulking agent ThermoFisher Scienti^cL-Leucine Amino acid ThermoFisher Scienti^c orMerck HPMC Pharmacoat 603 Viscosity modi^er Sigma Aldrich or HarkePharma -cyclodextrin ( -CD) Permeability enhancerSigma Aldrich or Merck and / or bulking agent Salcaprozate sodiumPermeability enhancer Chonginq Bioland(SNAC) Pharmaceutical Ltd Dodecyl phosphocholinePermeability enhancer Avanti Polar Lipids, Inc.(DPC) 3-O-Lauroyl-L-CartininePermeability enhancer Syngene InternationalHCl (LLC) Limited Milli-Q Water Solvent NanopharmEthanol Solvent Thermo Scienti^cSemaglutide API Shenzhen JYMedTechnology Co. Illustrative excipient packages are de^ned as shown in Table 3, which provides ranges of % w / w of components of the excipient packages, to be tested, based on the total weight of the excipient package (not on the total weight of the ^nal powder, which further comprise the GLP-1 receptor agonist, and may further comprise a binder and / or other components). Table 3: Formulations Excipient package type (All values in % Condition 1, Condition 1, Condition 2, Condition 2, Condition 3, w / w, based on Formulations Formulations Formulations Formulations Formulations the total weight 1-7 8-12 1-5 6-12 1-5 of the excipient package) HMPC 603 20-70 20-60 10-60 20-60 10-60 Mannitol 20-70 20-60 10-60 0-40 10-60 Leucine 0-10 0-10 10 0-10 10 Betadex 0-80 0-10 0-70 0-10 DPC 10 10-20 LLC 10 SNAC (All values in % Condition 3, Condition 4, Condition 4, Condition 4, w / w) Formulations Formulations Formulations Option 2, 6-12 1-4 5-12 Formulations 5-12 HMPC 603 20-60 10-35 0-30 22.5-35 Mannitol 0-40 5-30 0-30 22.5-35 Leucine 0-10 10 0-10 10 Betadex 0-70 0-10 0-20 DPC 0-10 LLC 10-20 0-10 SNAC 50 50-70 0-25 It will be understood that the % w / w amounts of components, when combined, cannot sum to a value of more than 100. For example, for a formulation having an excipient package consisting of the following components, which is Formulation 8 of Condition 4, Option 2: -HMPC 600 ^ 27.5 % w / w- Mannitol ^ 27.5% w / w- Leucine ^ 10 % w / w- DPC ^ 10 % w / w- SNAC ^ 25 % w / wThe components should be weighed, to provide the value for the ^weight of feedstock solids content^ in Equation 1 below. A spray dried powder is then prepared, by spray drying, from a solution of the components prepared in puri^ed water. Any suitable spray dryer may be used, such as a PROCEPT GMP Spray Dryer obtainable from PROCEPT nv (of Zele, Belgium) or a Buchi Spray Dryer obtainable from BUCHI UK Ltd (of Newmarket, U.K.). All spray dryer parts should be cleaned and dried before spray drying. Once spray dried, the resultant dry powder formulations should be weighed to determine the value for the ^weight of spray dried powder^ to calculate yield, using Equation 1 below. They should then be characterised in at least some, preferably all of the following ways. Analysis methods The exemplary formulations disclosed below were analysed by the following methods. Appearance The powder was inspected visually for one or more of the following characteristics, which may inform ease of collection of the powder. -Static charge- Aggregation (e.g., by reference to particle size distribution and powder rheology)- Adhesion to vessel- Moisture content (e.g., by reference to a Karl Fischer test)- Flowability (e.g., by reference to powder rheology)These characteristics can help inform how the powder should be handled and / or inform how the powder may change in characteristics over time. Moisture Content The moisture content was analysed by a colorimetric Karl Fischer test. Suitable powders tend to have a moisture content of less than 5 % w / w, based on the total weight of the powder formulation. The parameters described in Table 4 were used to determine the moisture content. Table 4: Moisture content measurement parameters Parameter Value Max drift (µg / mL) 25 Mix time (s) 60 Termination Drift relative, max 3600 seconds Oven temperature (ºC) 160 Air ^owrate (L / min) 100Particle Size Distribution (PSD) The particle size distribution of the prepared formulations was analysed using a Malven Mastersizer, obtainable from Malvern Panalytical of Malvern, U.K or Symaptec instrument. The parameters for determining PSD are provided in Table 5. Table 5: PSD parameters Parameter ValueLens R3 Feeder Speed (mm / s) 25 Pressure (bar) 3 Dispenser RODOS Trigger Condition ASPIROS R3The output data, Dv10, Dv50 and Dv90 indicates a cut-o particle size that 10%, 50% or90% by volume of the total particles collected, respectively, are smaller than. SPAN represents the width of distribution, calculated as SPAN = (Dv90 ^ Dv10) / Dv50 Size Exclusion Chromatography (SEC) Size exclusion chromatography (SEC) was used to determine the semaglutide content of the powder formulations immediately after formation (T = 0) and after 1 month (T = 1 month) of elevated temperature and humidity conditions, as described herein. Table 6 shows the detector and method that was used for SEC analysis. Table 6: SEC parameters Parameter Condition HPLC System and detector Agilent 1260 In^nity HPLC System consisting of quaternary pump, autosampler, UV detector Phase Size Exclusion Chromatography Column Waters Acquity BEH SEC 125, 1.7 µm, 150 mm x 4.6 mm Mobile phase Water, acetonitrile, isopropanol, tri^uoroacetic acid (35:52:13:0.1, v:v) Flow rate (mL / min) 0.200 Detection wavelength (nm) 220 Column temperature (°C) 35 ± 2 Autosampler temperature (°C) Ambient Injection volume (µL) 5.0 Elution method Isocratic Needle wash Water:ACN (50:50) Column washing procedure Wash column with 20% methanol and water for 45 mins. Only when necessary, wash the column with 20% methanol and water in reverse at a ^ow rate of 0.1000 Run time 10 min Yield The yield of the prepared formulation was determined using Equation 1: Equation 1 Yield (%) = [(weight of spray dried powder collected) / (weight of feedstock solids content introduced to spray dryer)]*100 RP-HPLC was used for semaglutide assay. Table 7 shows the method for reverse phase assay analysis. Table 7: Assay U-HPLC Parameter Condition U-HPLC System and detector Agilent 1260 In^nity U-HPLC System consisting of quaternary pump, autosampler, UV detector Phase Reverse Phase Column Acquity CSH C181.7 µm 150 x 2.1 mm Mobile phase Mobile phase A: 0.1% TFA in water / acetonitrile (90 / 10, v / v) Mobile phase B: 0.1% TFA in water / acetonitrile (10 / 90, v / v) Flow rate (mL / min) 0.225 Detection wavelength (nm) 220 Column temperature (°C) 30 ± 2 Autosampler temperature Ambient (°C) Injection volume (µL) 2.0 Elution method Time (min) Mobile Phase AMobile Phase B (%) (%) 0.00 66 342.00 66 3442.00 54 4642.10 66 3450.00 66 34Column washing procedure Milli-Q water : methanol (95:5) 15 minutes 100% acetonitrile 20 minutes Milli-Q water : acetonitrile (50 / 50, v / v) 15 minutes Run time 50 min Liquid formulation stability study Test were conducted to ascertain the level of absorption of a semaglutide API onto materials used in spray drying processes, i.e. glass, stainless steel and silicone. These tests revealed that the API does not absorb onto such materials and hence the need to include a surfactant in the formulation intended for use in spray drying (i.e. a liquid feedstock for dry powders) is alleviated. A mixture of an excipient or multiple excipients and the API were deemed compatible if one or more of the following criteria were met: (a) a visible completely solubilised liquid solution is formed; (b) an API assay has no interfering peaks from the excipient(s); (c) the U-HPLC trace is not less than 90% of a target; (d) the API integrity has high molecular weight species not less than 90% of the reference; (e) the dynamic light scattering (DLS) result show a polydispersity index (PDI) not more than 0.7, which indicates severe aggregation; and (f) the zeta potential is greater than ± 30 mV, a level which indicates a stable solution with no aggregation. A mixture of an excipient or multiple excipients and the API preferably meets at least 5, such as at least 6, ideally all of the above 7 criteria (a) to (g). In addition, for formulations and feedstocks for use in preparing dry powders by spray drying, the rheological pro^le advantageously has a viscosity suitable for spray drying. Test have been conducted to investigate the interaction between the semaglutide API and excipients in solution. Binary mixtures are used to explore the compatibility of the API with each excipient individually. Binary mixtures contained a 1:10 ratio of semaglutide to the excipient of interest were tested for each of the following excipients: mannitol, HPMC603, MPMC 606, -cyclodextrin, 2-hydroxypropyl- -cyclodextrin,dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), sodium salcaprozate (SNAC) and leucine. The solutions contained 1 mg / mL of the API and 10 mg / mL of the excipientin an aqueous 10 mM pH 7.2 sodium phosphate bu er solution.A semaglutide API has been found to be compatible with polysaccharides polymeric viscosity modi^ers, including cellulose derivatives and glycosaminoglycans especially cellulose ether derivatives such as hydroxypropyl methylcellulose. A semaglutide API has been found to be compatible with sugar alcohol bulking agents such as mannitol. A semaglutide API has been found to be compatible with -amino acids with non-polar, aliphatic side groups, such as leucine.The semaglutide API has been found to be compatible with -cyclodextrin ( -CD), 2-hydroxypropyl- -cyclodextrin (HP- -CD), dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC) and sodium salcaprozate (SNAC) permeability enhancers.A semaglutide API has been found to be compatible with phosphate bu er solutions. Inparticular the API has been found to be stable when in bu ered solutions of a pH of about7.2. The compatibility of a semaglutide API at a concentration of 1 mg / mL has also been evaluated for the following feedstock mixtures that contains multiple excipients: 1 mg / mL mannitol, 3 mg / mL HPMC 603, 1 mg / mL SNAC, 1 mg / mL -CD, 1 mg / mL DPC, 1mg / mL LLC, and 1 mg / mL leucine in an aqueous 10mM pH 7.2 sodium phosphate bu ersolution. 3 mg / mL mannitol; 1 mg / mL HPMC 603; 1 mg / mL SNAC; 1 mg / mL -CD; 1 mg / mL DPC;1 mg / mL LLC and 1 mg / mL leucine in an aqueous 10mM pH 7.2 sodium phosphate bu ersolution. 1 mg / mL HPMC 603; 3 mg / mL SNAC; 3 mg / mL -CD; 1 mg / mL DPC and 1 mg / mL LLC inan aqueous 10mM pH 7.2 sodium phosphate bu er solution.A liquid formulation comprising a semaglutide API has been found to have a good compatibility when the formulation includes an excipient package consisting of: from 20 to 70 % w / w of (a) at least one of a polymeric viscosity modi^er and a bulking agent, from 5 to 20 % w / w of (b) the amino acid component, and from 10 to 75 % w / w of (c) the permeability enhancer; especially from 30 to 60 % w / w of (a) at least one of a polymeric viscosity modi^er and a bulking agent, from 5 to 15 % w / w of (b) the amino acid component, and from 25 to 65 % w / w of (c) the permeability enhancer. The following excipient packages were evaluated under criteria (a) above: Excipientmannitol HPMC 603 L-leucine -CD SNACpackage 125% 25% 10% 40%3 25% 10% 25% 40%4 25% 10% 25% 40%6 20% 60% 20%7 20% 60% 20%8 20% 60% 20%It was observed that the SNAC did not fully dissolve in when the excipient packages 1, 3 and 4 were prepared as a 30 mg / mL solution, i.e. containing 12 mg / mL of SNAC. However, when excipient packages 6, 7 and 8 were prepared as a 30 mg / mL solution, i.e. containing 6 mg / mL of SNAC the formulations dissolved more readily. The formulation prepared with excipient package 6 was completely clear with slight yellow colouration, the formulation prepared with excipient package 7 was milky with slight yellow colouration and the formulation prepared with excipient package 8 was milky with no yellow colouration. The above results suggest that the permeability enhancer sodium salcaprozate (SNAC) is not fully soluble at a concentration in excess of 10 mg / mL in formulations also containing a HPMC viscosity modi^er and / or mannitol bulking agent and L-leucine. It has further been observed that polymeric viscosity modi^ers, such as HPMC, enhance the solubility of permeability enhancers, such as SNAC. It has further been observed that while some permeability enhancers, such as SNAC, are sparingly soluble in aqueous solutions, their solubility increases in solutions also including GLP-1 agonists, such as semaglutide. Exemplary dry powder formulations Exemplary feedstock formulations were prepared by dissolving in a solvent of water:ethanol (35:65 v / v), the excipients shown in Table 8. Semaglutide was weighed and added to the solution under controlled conditions of room temperature and relative humidity less than 10%. Semaglutide was added to the solution no more than 30 minutes before spray drying to prevent degradation of semaglutide. The total solid content of the solution formed was 8.0 % w / v. After addition of semaglutide to the solution, the solution was mixed by gentle agitation by hand swirling and vigorous stirring or vortexing was avoided. For the avoidance of doubt, solid content is reported as weight percent relative all solids of the formulation (e.g. excipients and API) unless otherwise stated. The dry powders were then formed by spray drying. Spray drying conditions are described in table 9. Table 9: Spray drying parameters Parameter Name Value Water bath (ºC) 23 ± 2 Agitation (RPM) 100 Feed rate (ml / min) 0.5 Feeding tube size LS13 Occlusion bite (#) 4 Nozzle type Ultrasonic Power (Watts) 13 Nozzle temperature (ºC) 60 Cooling gas ^ow rate L / min 45 Drying gas ^ow rate L / min 600 Output gas ^ow rate L / min 100 Inlet temperature (ºC) 115 ± 5 Output temperature (ºC) 100 ± 5 Batch Duration (min) 180 ± 10 Visual inspection of the powder formulations obtain indicated minimal static, white colour powder which was easy to collect from the drying chamber. Powders were characterised for their yield, size and the results are shown in Table 8. Table 8 also includes the viscosity of the feedstock solution. As shown in table 8, the yield obtained ranged between 15 and 24 %. It was observed that a higher content of HPMC increased the viscosity of the feedstock. For example, formulation 1 had highest HPMC content and highest viscosity, whilst formulations 11 and 12 had the lowest amount of HPMC or were absent HPMC and had the lowest viscosities. It was also observed that increasing the ratio of permeation enhancer:semaglutide, decreased the viscosity (e.g. formulation 4 vs formulation 8, formulation 3 vs formulation 7). The moisture content, particle size distribution parameters and semaglutide content of the dry powders formed from spray drying formulations was analysed immediately after preparation (T=0) and the results are shown in Table 10a. The moisture content of the spray dried powders at T=0 ranged from 0.38% to 0.63%. It isbelieved that a mixture of ethanol and water in the solvent is e ective in removing waterduring the spray drying process. A lower water content in the solvent may also improve stability for semaglutide in solution by reducing the risk of hydrolytic degradation. Semaglutide content of the spray dried powders was determined by U-HPLC and SEC analysis. The content of semaglutide is reported relative to the semaglutide content of the feedstock formulation. Thus, an assay of less than 100% indicates a loss in semaglutide content, such as by degradation or decomposition. U-HPLC assay for the powders at T = 0 showed an acceptable semaglutide content across all formulations with the exception of spray dried powders formed from formulations 1, 3 and 7 for which U-HPLC analysis determined a semaglutide content of less than 90%. Analysis by SEC of semaglutide content of the powders formed from formulations 1 and 3 determined an acceptable semaglutide content, whilst the semaglutide content of the powder formed from formulation 7 was again signi^cantly below 100%. This indicates that LLC, particularly at higher concentrations, may be detrimental to semaglutide stability. The spray dried powders have Dv10, Dv50 and Dv90 values ranging from 6.22 m to 10.99 m, 18.27 m to 21.82 m, and 20.37 m to 38.83 m, respectively. Span values ranged between 1.098 and 1.572. A narrow span suggests particle size uniformity which is important for pulmonary delivery. It is believed that HPMC may improve particle size distribution, especially Dv10. The powder formed from formulation 8 comprised a HPMC content of 60 % w / w, a DPC content of 30 % w / w and a semaglutide content of 10 % w / w and had a Dv10 of 9.25 µm.Formulation 11 di ered in that the HPMC of formulation 8 was replaced by -cyclodextrinand had a Dv10 of 6.24 µm. An increase in Dv10 is important for nasal delivery of particles by the pulmonary route to reduce the number of particles of small enough size to be inhaled. ,

[0002] Long-term stability studies of exemplary dry powder formulations To investigate the long-term stability of the spray dried powders described in Table 8, the powders were stored for one month at elevated temperature and humidity. Stability studies are typically conducted at elevated temperature and humidity to accelerate degradation that may be seen over the longer term at room temperature and lower humidity i.e. typical conditions for inhaler storage in the home. Powders formed from formulations 1 to 10 described in Table 8 were characterized after 1 month (T = 1 month) of storage at 25 °C and 60% relative humidity (% RH) or 40 °C and 75% RH, as indicated in Table 10b. The powders were characterised for moisture content, by particle size analysis, and semaglutide assay using U-HPLC and SEC. No signi^cant increase in moisture content was observed with measured moisture content at T 1month ranging from 0.66 to1.19%. PSD analysis showed that the powders formed from formulations 2, 6 and 9 showed an increase in PSD at T = 1 month at 25 °C and 60% RH. The powder formed from formulation 2 exhibited an especially large increase in Dv10 from 10.53 µm at T= 0 to 27.93 µm at T= 1month. The powder prepared from formulation 7 exhibited a very large increase in Dv90 at T =1month to a value of 797.11 m and having heterogeneous PSD with multiple sizespecies. This overt increase in Dv90 was re^ected on the increase in the SPAN values. The SPAN values of formulation 7 was 27.44. The powders formed from formulations 8 and 10 showed good performance in terms of particle size distribution, semaglutide stability and long-term stability. Where in the foregoing description, features or limitations are mentioned which have equivalents that are known, evident or foreseeable to those skilled in the art in the light of the present invention, then such equivalents are incorporated herein as if particularly set forth. Reference should be made primarily to the claims for determining the scope of the subject-matter of the present invention. The scope of protection sought by the present application further encompasses any such equivalents. It will also be appreciated by those skilled in the art that features or limitations of the disclosed subject-matter that are described as preferable, suitable, advantageous, convenient or the like may be optional and may not limit the scope of the independent claim(s) or the protection sought unless explicitly stated otherwise. Moreover, it is to be understood that such optional features or limitations, while of potential bene^t in some implementations of the disclosed subject-matter, may be undesirable, and may therefore be absent or omitted in other implementations.

Claims

CLAIMS 1. A dry powder formulation in the form of a solid particulate powder, the dry powderformulation being for nasal delivery or delivery by inhalation, and comprising or consisting of: -at least one of a polymeric viscosity modi^er and a bulking agent;- a permeability enhancer;- an optional amino acid component; and- a glucagon-like peptide-1 (GLP-1) receptor agonist.

2. The dry powder formulation as de^ned in claim 1, wherein the GLP-1 receptoragonist comprises or consists of semaglutide.

3. The dry powder formulation as de^ned in any preceding claim, further comprisinga binder.

4. The dry powder formulation as de^ned in any preceding claim, wherein theviscosity modi^er comprises or consists of one or more cellulose ether derivatives.

5. The dry powder formulation as de^ned in claim 4, wherein the viscosity modi^ercomprises or consists of hydroxypropyl methylcellulose (HPMC).

6. The dry powder formulation as de^ned in any preceding claim, wherein theviscosity modi^er is present in an amount of 2-75 % w / w based on the total weight of the following, taken together: the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and (if present) the optional amino acid component.

7. The dry powder according to claim 6, wherein the viscosity modi^er is present inan amount of 45 to 75 % w / w based on the total weight of the following, taken together the polymeric viscosity modi^er; (if present) the bulking agent; the permeability enhancer; and (if present) the optional amino acid component.

8. The dry powder formulation as de^ned in any preceding claim, wherein a 2% (w / w)solution in water at 20 °C of the viscosity modi^er has a dynamic viscosity of from 1.5 to 20 mPas.

9. The dry powder formulation as de^ned in any preceding claim, wherein the bulkingagent comprises or consists of one or more sugar alcohols.

10. The dry powder formulation as de^ned in claim 9, wherein the bulking agentcomprises or consists of mannitol.

11. The dry powder formulation as de^ned in any preceding claim, wherein the aminoacid comprises or consists of one or more -amino acids with non-polar, aliphatic side groups.

12. The dry powder formulation as de^ned in claim 11, wherein the amino acidcomprises or consists of L-leucine.

13. The dry powder formulation as de^ned in any preceding claim, wherein thepermeability enhancer comprises or consists of one or more of:- one or more cyclodextrins;- one or more phosphocholines;- one or more fatty acid esters of carnitine; and- at least one salt of a fatty acid having a chain length of from 6 to 22-carbon atomsoptionally substituted an aromatic group.

14. The dry powder formulation as de^ned in claim 13, wherein the permeabilityenhancer comprises or consists of one or more of the following: -cyclodextrin, 2- hydroxypropyl- -cyclodextrin, DPC, LLC and SNAC.

15. The dry powder formulation as de^ned in claim 14, wherein the permeabilityenhancer comprises or consists of one or more of the following: -cyclodextrin, DPC, LLC and SNAC.

16. The dry powder formulation as de^ned in any preceding claim, having a moisturecontent of less than 5 % w / w, measured relative to the total weight of the powder formulation.

17. The dry powder formulation as de^ned in any preceding claim, the solidparticulate powder having a D50 in a range of 1-5 µm.

18. The dry powder formulation as de^ned in claim 17, which is for delivery byinhalation.

19. The dry powder formulation as de^ned in any one of claims 1 to 16, wherein nomore than 10 % v / v of the particles of the solid particulate powder have a diameter of less than 10 µm.

20. The dry powder formulation as de^ned in any one of claims 1 to 16 or 19, the solidparticulate powder having a D50 in a range of 20-50 µm.

21. The dry powder formulation as de^ned in claim 19 or claim 20, which is for nasaldelivery.

22. A dosage form for nasal delivery or inhalation, comprising the dry powderformulation as de^ned in any one of the preceding claims.

23. A liquid formulation comprising:(i) a GLP-1 agonist,(ii) an excipient package consisting of: (a) at least one of a polymericviscosity modi^er and a bulking agent, (b) an optional amino acid component, (c) a permeability enhancer and (d) an optional binder; (iii) a liquid carrier;and optionally (iv) a bu er.

24. The liquid formulation of claim 23, wherein the GLP-1 agonist is semaglutide.

25. The liquid formulation of claim 23 or claim 24, wherein the polymeric viscositymodi^er is a polysaccharide, especially hydroxypropyl methylcellulose (HPMC).

26. The liquid formulation of any one of claims 23 to 25, wherein a 2% (w / w) solutionin water at 20 °C of the polymeric viscosity modi^er has a dynamic viscosity of from 1.5 to 20 mPas.

27. The liquid formulation of any one of claims 23 to 26, wherein the bulking agent isa sugar alcohol bulking agent, especially mannitol.

28. The liquid formulation of any one of claims 23 to 27, wherein the amino acidcomponent includes an -amino acid with a non-polar, aliphatic side chain, especially L-leucine.

29. The liquid formulation of any one of claims 23 to 28, wherein the permeabilityenhancer is selected from one or more of a cyclodextrin, a phosphocholine, a fatty acid ester of carnitine, a salt of a fatty acid having a chain length of from 6 to 22-carbon atoms optionally substituted with an aromatic group, and a medium- chain fatty acid ester having a chain length of from 6 to 22-carbon atoms in the fatty acid portion.

30. The liquid formulation of any one of claims 23 to 29, wherein the permeabilityenhancer is selected from one or more of -cyclodextrin, 2-hydroxypropyl- -cyclodextrin, dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), and sodium salcaprozate (SNAC).

31. The liquid formulation of any one of claims 23 to 30, wherein the excipientpackage consists of (a) at least one of a polymeric viscosity modi^er and a bulking agent in a total amount of from 20 to 70 % w / w, (b) the amino acid component in an amount of from 5 to 20 % w / w, (c) the permeability enhancer in an amount of from 10 to 75 % w / w and (d) an optional binder, wherein the amounts are based on the total weight of the excipient package.

32. The liquid formulation of any one of claims 23 to 30, wherein the excipientpackage consists of (a) at least one of a polymeric viscosity modi^er and a bulking agent in a total amount of from 30 to 60 % w / w, (b) the amino acid component in an amount of from 5 to 15 % w / w, (c) the permeability enhancer in an amount of from 25 to 65 % w / w and (d) an optional binder, wherein the amounts are based on the total weight of the excipient package.

33. The liquid formulation of claim 23, wherein the excipient package consists of: (a)both a polysaccharide viscosity modi^er and a sugar alcohol bulking agent, (b) an -amino acid with a non-polar, aliphatic side chain, (c) a permeability enhancer selected from one or more of a -cyclodextrin, 2-hydroxypropyl- -cyclodextrin dodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), and sodium salcaprozate (SNAC) and (d) an optional binder.

34. The liquid formulation of claim 23, wherein the excipient package consists of: (a)both a polysaccharide viscosity modi^er and a sugar alcohol bulking agent in a total amount of from 20 to 70 % w / w, (b) an -amino acid with a non-polar, aliphatic side in an amount of from 5 to 20 % w / w, (c) a permeability enhancer selected from one or more of a -cyclodextrin, 2-hydroxypropyl- -cyclodextrindodecylphosphocholine (DPC), lauroyl-L-carnitine (LLC), and sodium salcaprozate (SNAC) in a total amount from 10 to 75 % w / w and (d) an optional binder, wherein the amounts are based on the total weight of the excipient package.

35. The liquid formulation of claim 23, wherein the excipient package consists of: (a)one or both of a hydroxypropyl methylcellulose viscosity modi^er and a mannitol bulking agent in a total amount of from 20 to 70 % w / w, (b) leucine in an amount of from 5 to 20 % w / w, (c) a permeability enhancer selected from one or more of a-cyclodextrin, 2-hydroxypropyl- -cyclodextrin dodecylphosphocholine (DPC),lauroyl-L-carnitine (LLC), and sodium salcaprozate (SNAC) in a total amount from 10 to 75 % w / w and (d) an optional binder, wherein the amounts are based on the total weight of the excipient package.

36. The liquid formulation of any one of claims 23 to 35 wherein the permeabilityenhancer is sodium salcaprozate (SNAC) and the concentration of SNAC in the formulation is optionally 10 mg / mL or less.

37. The liquid formulation of claim 36, wherein the polymeric viscosity modi^er ishydroxypropyl methylcellulose, wherein the excipient package optionally consists of no more than 30 % w / w sodium salcaprozate and at least 40 % w / w hydroxypropyl methylcellulose.

38. The liquid formulation of any one of claims 23 to 37, wherein the pH of theformulation is between 6.7 and 7.7.

39. The liquid formulation of any one of claims 23 to 38, wherein a phosphate bu eris present.

40. A dosage form for nasal delivery comprising the liquid formulation of any one ofclaims 23 to 39.

41. A liquid feedstock for preparing a dry power, the liquid feedstock comprising theliquid formulation of any one of claims one of claims 23 to 39.

42. The liquid formulation, feedstock or dosage form of any one of claims 23 to 41that includes no more than 0.001 % w / w of surfactant, based on the total weight of the liquid formulation, feedstock or dosage form.

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