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US-20260124143-A1 - NEW PHARMACEUTICAL COMPOSITION FOR DRUG DELIVERY

US20260124143A1US 20260124143 A1US20260124143 A1US 20260124143A1US-20260124143-A1

Abstract

According to the invention, there is provided a pharmaceutically-acceptable composition which is preferably in the form of a spray-dried powder comprising a mixture of: (fffffffffffff) a pharmacologically-effective dosage amount of at least one pharmaceutically-active compound; and (ggggggggggggg) a pharmaceutically-acceptable carrier material, which carrier material comprises a combination of a disaccharide and a polymeric material. Compositions are suitable for, for example, transmucosal drug delivery, including sublingual and nasal delivery. In the case of nasal delivery, said compositions may be loaded into single- or multiple-use nasal applicators. Preferred pharmaceutically-acceptable carriers in this regard include lactose or trehalose and dextrins (e.g. cyclodextrins or maltodextrins), which may be spray-dried together in combination. Compositions may further comprise one or more alkyl saccharides. Preferred alkyl saccharides include sucrose esters, such as sucrose monolaurate.

Inventors

  • Jonas Sävmarker
  • Robert Rönn
  • Andreas Fischer

Assignees

  • OREXO AB

Dates

Publication Date
20260507
Application Date
20250611
Priority Date
20200518

Claims (20)

  1. 1 . (canceled)
  2. 2 . A composition in the form of an amorphous powder, which amorphous powder comprises particles and is essentially free of water, wherein said amorphous powder comprises: (a) a pharmacologically-effective dosage amount of a glucagon-like peptide- 1 (GLP-1) receptor agonist or a pharmaceutically-acceptable salt thereof, and (b) a pharmaceutically-acceptable carrier material, which carrier material comprises a combination of a disaccharide and a polymeric material; wherein the particles of the amorphous powder comprise an amorphous composite of said GLP-1 receptor agonist or salt thereof and the carrier material.
  3. 3 . The composition as claimed in claim 2 , wherein the disaccharide is selected from the group consisting of maltitol, trehalose, sucralose, sucrose, isomalt, maltose and lactose.
  4. 4 . The composition as claimed in claim 3 , wherein the disaccharide comprises lactose or trehalose.
  5. 5 . The composition as claimed in claim 2 , wherein the polymeric material comprises polyvinylpyrrolidone, a dextrin and/or hydroxypropylmethyl cellulose.
  6. 6 . The composition as claimed in claim 2 , wherein the polymeric material comprises a dextrin and/or hydroxypropylmethyl cellulose.
  7. 7 . The composition as claimed in claim 6 , wherein the dextrin comprises a cyclodextrin or a maltodextrin.
  8. 8 . The composition as claimed in claim 2 , wherein the carrier material comprises a combination of: (i) lactose or trehalose; and (ii) a maltodextrin.
  9. 9 . The composition as claimed in claim 2 , wherein the ratio of disaccharide:polymeric material by weight is in the range of about 10:1 and about 1:20.
  10. 10 . The composition as claimed in claim 9 , wherein the ratio of disaccharide:polymeric material by weight is in the range of about 2:1 and about 1:10.
  11. 11 . The composition as claimed in claim 2 , wherein the lowest measurable glass transition temperature of the composition is at least about 40° C. when measured at a relative humidity of up to about 35%.
  12. 12 . The composition as claimed in claim 2 , wherein the composition further comprises a surfactant.
  13. 13 . The composition as claimed in claim 12 , wherein the surfactant comprises a sucrose ester.
  14. 14 . The composition as claimed in claim 13 , wherein the sucrose ester comprises sucrose monolaurate.
  15. 15 . The composition as claimed in claim 2 , wherein the powder has a particle size distribution that allows for an effective dose of said GLP-1 receptor agonist, or salt thereof, to be deposited on the nasal mucosa upon intranasal administration.
  16. 16 . The composition as claimed in claim 2 , wherein the powder has a particle size distribution that includes a D10 that is above about 3 μm.
  17. 17 . The composition as claimed in claim 16 , wherein the particle size distribution includes a D10 above about 10 μm.
  18. 18 . The composition as claimed in claim 17 , wherein the particle size distribution includes a D90 below about 500 μm.
  19. 19 . The composition as claimed in claim 18 , wherein the particle size distribution includes a D90 below about 100 μm.
  20. 20 . The composition as claimed in claim 2 , wherein the powder has a particle size distribution that includes a volume-based mean diameter within the range of about 10 μm and about 100 μm.

Description

This application is a continuation of U.S. patent application Ser. No. 18/345,770, filed Jun. 30, 2023, which is a continuation of U.S. patent application Ser. No. 17/540,929, filed Dec. 2, 2021, which is a continuation of PCT Application No. PCT/GB2021/051191, filed May 18, 2021, which is hereby incorporated by reference in its entirety, and which claims the priority benefit of GB 2018901.5, filed Dec. 1, 2020, GB 2009905.7, filed Jun. 29, 2020, and GB 2007306.0, filed May 18, 2020. This invention relates to new pharmaceutical compositions that are useful in a variety of medical conditions. The invention also relates to methods of manufacturing such compositions and formulating them into dosage forms. PRIOR ART AND BACKGROUND The listing or discussion of an apparently prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or common general knowledge. Among the various well-known routes of the drug delivery, peroral delivery to the gastrointestinal tract is the most common. It is generally regarded as being the most favoured by the patients and practitioners. However, peroral drug administration is known to have specific drawbacks, including the fact that active ingredients are necessarily subject to hepatic first-pass metabolism and also enzymatic degradation within (and outside) the gastrointestinal tract. This may affect the efficacy of certain drugs and, in some cases, may even disqualify it as an administration route altogether. Peroral administration to the gastrointestinal tract has the additional disadvantage that it requires absorption of active ingredients through the intestines as part of the digestive process, which takes time. In the treatment of certain conditions, such as acute disorders, a more rapid onset of pharmacological effect is often highly desirable. In such cases, administration principles in which drugs are immediately absorbed into systemic circulation is more likely to lead to a rapid onset of action. Although this can be done via parenteral administration (such as subcutaneous or intravenous injection), such delivery means are inconvenient, and are sometimes very difficult and/or impossible for patients to do, requiring time-consuming intervention by physicians to ensure compliance and avoid effects that are either unwanted or detrimental. Transmucosal administration of active ingredients is a viable alternative to 5 parenteral administration. It gives rise to the possibility of delivering drug molecules directly into systemic circulation through mucosal membranes (e.g. rectally, sublingually, buccally, pulmonarily and intranasally), and may lead to advantages, such as increased patient compliance, improved drug bioavailability, a more rapid onset of action and reduced side effects. However, transmucosal administration of drugs presents its own, quite distinct problems. Unlike the gastrointestinal tract, which is a large organ that contains a relatively large amount of biological fluids, spaces such as the oral and nasal cavities are relatively small and contain much lower amounts of bodily fluids, such as saliva and/or mucous. This inevitably provides a considerable limitation on the amount of active ingredient that can be administered in a single dose. Furthermore, although it is a dynamic system, the gastrointestinal tract is, in the main part, something of a ‘closed’ system. Conversely, the rapid clearance mechanisms that take place in both the oral and nasal cavities means that the time that is often available for absorption across a mucosal surface, for an already more limited amount of drug, is also limited. Numerous formulation principles have been put forward to solve this problem, including, for example, bioadhesive formulation principles, such as buccal patches for oromucosal drug delivery (see, for example, Shojaei, J. Pharm. Pharmaceutical Sci., 15, 19 (1998) and Gandhi, Advanced Drug Delivery Reviews, 43, 67 (1994)), as well as in situ gelling compositions for intranasal drug delivery (see, for example, Bertan et al, Eur. J. Pharm. Sci., 27, 62 (2006)). Transmucosal drug delivery systems that are in the solid state may present a significant advantage in allowing for higher drug loadings in the formulation. However, although solid drug delivery compositions are far more common when administering to rectal, buccal, sublingual and pulmonary mucosae, it remains the case that the vast majority of intranasal drug delivery systems are presented in the form of liquid sprays, typically aqueous solutions, wherein drug solubility plays yet another limiting factor in the amount of drug that is available for absorption. That liquid sprays for intranasal delivery are almost ubiquitous is because formulating solid pharmaceutical formulations in form of a nasal powder is not easy. Unlike powders that are frequently employed for inhalation of active ingredients into the lungs, there are