Abstract: The invention relates to polymorphic forms of the calcium salt of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester. The calcium salt of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester is useful in the treatment of various conditions and disorders responsive to the inhibition of neutral endopeptidases.

Abstract: A method of preparing a pharmaceutical product comprises the steps of (a) providing a neat active pharmaceutical ingredient (API) complying with at least five of the following parameters determined by using a FT4 powder rheometer: (i) specific basic flow energy of at most 60 mJ/g; (ii) stability index of 0.75 to 1.25; (iii) specific energy of at most 10 mJ/g; (iv) major principle stress at 15 kPa of at most 40; (v) flow function at 15 kPa of at least 1.3; (vi) consolidated bulk density at 15 kPa of at least 0.26 g/mL; (vii) compressibility of at most 47%; and (viii) wall friction angle of at most 40°; (b) dispensing the neat API of step (a) into a bottom part of a pharmaceutical carrier using a vacuum assisted metering and filling device; and (c) encapsulating the bottom part, thereby producing a pharmaceutical product.

Abstract: A formulation for injection moulding of a pharmaceutical carrier comprising 27-85% (w/w) of polyvinyl alcohol, and 10-60% (w/w) of a disintegration aid selected from maize starch, wheat starch, and combinations thereof; and optionally one or more excipients.

Abstract: The present invention relates to methods of preparing pharmaceutical products, involving filling active pharmaceutical ingredient powders into pharmaceutical carriers with a vacuum assisted metering and filling device. The methods disclosed herein can be used in a continuous process, such as in a high-throughput process for producing a pharmaceutical product. The present invention further relates to a particular quality of the neat active pharmaceutical ingredient (API) HDM201, i.e. siremadlin, present as succinic acid co-crystal, which can be used in the methods of preparation of the present invention.

Abstract: A gauge comprising an elongate rod and a head. The rod has an elongate axis. The head has a transverse dimension perpendicular to the elongate axis of the rod. The gauge has an insertion configuration and an inspection configuration, wherein the transverse dimension of the head is greater in the inspection configuration than in the insertion configuration. The head comprises two head portions each with a longitudinally-extending outer surface and a longitudinally-extending inner surface and, in the insertion configuration, the inner surfaces of the head portions are at least partly in abutment with each other. The gauge can be used in a method of measuring an internal dimension of a bore within a component.

Abstract: A method of preparing a pharmaceutical product comprises the steps of (a) providing a neat active pharmaceutical ingredient (API) complying with at least five of the following parameters determined by using a FT4 powder rheometer: (i) specific basic flow energy of at most 60 mJ/g; (ii) stability index of 0.75 to 1.25; (iii) specific energy of at most 10 mJ/g; (iv) major principle stress at 15 kPa of at most 40; (v) flow function at 15 kPa of at least 1.3; (vi) consolidated bulk density at 15 kPa of at least 0.26 g/mL; (vii) compressibility of at most 47%; and (viii) wall friction angle of at most 40°; (b) dispensing the neat API of step (a) into a bottom part of a pharmaceutical carrier using a vacuum assisted metering and filling device; and (c) encapsulating the bottom part, thereby producing a pharmaceutical product.

Abstract: A formulation for injection molding of a pharmaceutical carrier comprises 43.5-97% (w/w) of one or more polyethylene oxide polymer having a weight average molecular weight of MW 94,000-188,000; and optionally one or more excipients.

Abstract: A pharmaceutical carrier (20) comprises a lid part (22) and a bottom part (24), wherein at least one of the lid part (22) and the bottom part (24) has a first wall section (26, 30) with a thickness of 180-250 ?m, preferably 185-225 ?m, even more preferably 190-220 ?m, and most preferably about 215 ?m, and a second wall section (28, 32) with a thickness of 350-450 ?m, preferably 375-425 ?m, more preferably 390-410 ?m, and most preferably about 400 ?m. The first wall section (26) of the lid part (22) defines an entire top portion of the lid part (22). Alternatively or additionally thereto, the first wall section (30) of the bottom part (24) defines an entire bottom portion of the bottom part (24).

Abstract: The invention relates to polymorphic forms of the calcium salt of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester. The calcium salt of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester is useful in the treatment of various conditions and disorders responsive to the inhibition of neutral endopeptidases.

Abstract: The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a ?-amino-?-biphenyl-?-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Abstract: The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a ?-amino-?-biphenyl-?-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.

Abstract: The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a g-amino-d-biphenyl-a-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Abstract: The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a ?-amino-?-biphenyl-?-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.

Abstract: The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a ?-amino-?-biphenyl-?-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.

Abstract: The present invention relates to pyrrolidin-2-ones according to the formula (1), or salts thereof, wherein R1 is hydrogen or a nitrogen protecting group, methods for their preparation and their use in the preparation of NEP-inhibitors, particularly in the preparation of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Abstract: The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a ?-amino-?-biphenyl-?-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Abstract: The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a g-amino-d-biphenyl-a-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Abstract: The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a ?-amino-?-biphenyl-?-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.

Abstract: The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a -amino- -biphenyl- -methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Abstract: The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a g-amino-d-biphenyl-a-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.