PMID- 29499299
OWN - NLM
STAT- MEDLINE
DCOM- 20180925
LR  - 20180925
IS  - 1873-3441 (Electronic)
IS  - 0939-6411 (Linking)
VI  - 127
DP  - 2018 Jun
TI  - Formulating monoclonal antibodies as powders for reconstitution at high 
      concentration using spray drying: Models and pitfalls.
PG  - 407-422
LID - S0939-6411(17)31347-4 [pii]
LID - 10.1016/j.ejpb.2018.02.002 [doi]
AB  - In anticipation of non-invasive routes capable of delivering adequately high, 
      systemic monoclonal antibody (mAb) concentrations, subcutaneous (SC) injection is 
      arguably the most patient friendly alternative administration route available for 
      this drug class. However, due to the limited volume that can be administered 
      through this route and mAbs' relatively low therapeutic activity, solutions for 
      subcutaneous injection often need to be highly concentrated, making them 
      inherently more prone to potentially detrimental protein (self-) interaction, 
      which is why mAb formulations for SC injection and other highly concentrated mAb 
      solutions are often dried to increase their stability. In this work we 
      investigated spray drying (SD) as a drying technique for formulating mAbs as 
      powders for reconstitution, assessing the influence of SD process parameters, as 
      well as excipients present in the feed solution on both mAb stability and 
      relevant powder characteristics for reconstitution using a model mAb. By 
      employing a design of experiments approach, we were able to provide statistically 
      substantiated evidence for the reconstitution time reducing and stability 
      improving properties of l-arginineHCl, l-histidineHCl, l-lysineHCl and 
      polysorbate 20 when combined with a disaccharide in SD mAb powders for 
      reconstitution. Additionally, the study yielded several statistical models 
      describing process parameter influences on relevant powder and mAb stability 
      characteristics.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Batens, Maarten
AU  - Batens M
AD  - Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
FAU - Massant, Jan
AU  - Massant J
AD  - Biological Formulation Development, UCB Pharma, Braine l'Alleud, Belgium.
FAU - Teodorescu, Bianca
AU  - Teodorescu B
AD  - Non-Clinical Statistics, UCB Pharma, Braine l'Alleud, Belgium.
FAU - Van den Mooter, Guy
AU  - Van den Mooter G
AD  - Drug Delivery and Disposition, KU Leuven, Leuven, Belgium. Electronic address: 
      guy.vandenmooter@kuleuven.be.
LA  - eng
PT  - Journal Article
DEP - 20180227
PL  - Netherlands
TA  - Eur J Pharm Biopharm
JT  - European journal of pharmaceutics and biopharmaceutics : official journal of 
      Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
JID - 9109778
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Excipients)
RN  - 0 (Powders)
SB  - IM
MH  - Antibodies, Monoclonal/*chemistry
MH  - Chemistry, Pharmaceutical/methods
MH  - Desiccation/methods
MH  - Drug Compounding
MH  - Excipients/chemistry
MH  - Freeze Drying/methods
MH  - Injections, Subcutaneous/methods
MH  - Particle Size
MH  - Powders/*chemistry
OTO - NOTNLM
OT  - Amino acid
OT  - Design of experiments
OT  - Disaccharide
OT  - High concentration
OT  - Monoclonal antibody
OT  - Protein formulation
OT  - Reconstitution
OT  - Spray drying
OT  - Stability
OT  - Surfactant
EDAT- 2018/03/03 06:00
MHDA- 2018/09/27 06:00
CRDT- 2018/03/03 06:00
PHST- 2017/11/23 00:00 [received]
PHST- 2018/02/01 00:00 [revised]
PHST- 2018/02/01 00:00 [accepted]
PHST- 2018/03/03 06:00 [pubmed]
PHST- 2018/09/27 06:00 [medline]
PHST- 2018/03/03 06:00 [entrez]
AID - S0939-6411(17)31347-4 [pii]
AID - 10.1016/j.ejpb.2018.02.002 [doi]
PST - ppublish
SO  - Eur J Pharm Biopharm. 2018 Jun;127:407-422. doi: 10.1016/j.ejpb.2018.02.002. Epub 
      2018 Feb 27.