Process and purification for manufacture of a modified insulin intended for oral delivery.
Oral delivery of insulin is convenient and physiologically desirable in the treatment of diabetes. However, this route of administration has presented substantial challenges as insulin is degraded enzymatically in the gut, resulting in low bioavailability. We have developed a conjugated insulin product (IN-105) that has high bioavailability and is currently undergoing clinical trials for the treatment of diabetes. A process for the manufacture of IN-105 was developed. Initially, recombinant human insulin was conjugated covalently with a monodisperse, short-chain methoxypolyethylene glycol derivative. The desired product, IN-105, was purified from its closely related species using RP-HPLC and cation exchange chromatography to a purity of 98.5%. The elution pool from cation exchange chromatography was crystallized and lyophilized into the dry active pharmaceutical ingredient.
Research and Development, Biocon Ltd., 20th KM Hosur Road, Electronic City, Bangalore, India. nitesh.dave@biocon.com
Nitesh
N
Dave
Partha
P
Hazra
Anand
A
Khedkar
H S
HS
Manjunath
Harish
H
Iyer
Shrikumar
S
Suryanarayanan
D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D002852:Chromatography, Ion Exchange / Q000379:methods; D003460:Crystallization; D005612:Freeze Drying; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000302:isolation & purification*; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet
D007004:Hypoglycemic Agents; D007328:Insulin; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol