PMID- 25087508
OWN - NLM
STAT- MEDLINE
DCOM- 20150514
LR  - 20140901
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 473
IP  - 1-2
DP  - 2014 Oct 1
TI  - Low-dose capsule filling of inhalation products: critical material attributes and 
      process parameters.
PG  - 617-26
LID - S0378-5173(14)00549-3 [pii]
LID - 10.1016/j.ijpharm.2014.07.050 [doi]
AB  - The aim of the present work was to identify the material attributes and process 
      parameters of a dosator-nozzle capsule filling machine that are critical in 
      low-fill weight capsule filling for inhalation therapies via hard-gelatin 
      capsules. Twelve powders, mostly inhalation carriers, some fines and one 
      proprietary active pharmaceutical ingredient (API), were carefully characterized 
      and filled into size 3 capsules. Since different process conditions are required 
      to fill capsules with powders that have very different material attributes, the 
      powders were divided into two groups. A design of experiments (DOE) based 
      exclusively on process parameters was developed for each group, to identify the 
      critical material attributes (CMA) and critical process parameters (CPP). The 
      fill weight (4-45 mg) of the group I powders (larger particles, higher density, 
      better flowability and less cohesion) correlated with the nozzle diameter 
      (1.9-3.4mm), the dosing chamber length (2.5-5mm), the powder layer depth 
      (5-12.5mm) and the powder density (bulk and tapped density). The RSDs were 
      acceptable in most cases, even for very low doses. The fill weight (1.5-21 mg) of 
      group II powders (very fine and low dense particles with a particle size <10 mum, 
      poor flowability and higher cohesion) depended also on the nozzle diameter 
      (1.9-2.8mm), the dosing chamber length (2.5-5mm) and the powder layer depth 
      (5-10mm), albeit in a different way, indicating that for these powders dosator 
      filling was not volumetric. Moreover, frictional (wall friction angle) and 
      powder-flow characteristics (bulk density and basic flowability energy) have an 
      influence on the mass. Thus, in summary, group I and group II powders can be 
      filled successfully via dosator systems at low fill weights. However, the group 
      II powders were more challenging to fill, especially without automated process 
      control. This study is the first scientific qualification of dosator nozzles for 
      low-fill weight (1-45 mg) capsule filling.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Faulhammer, Eva
AU  - Faulhammer E
AD  - Technical University, Inffeldgasse 13, 8010 Graz, Austria; Research Center 
      Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria.
FAU - Fink, Marlies
AU  - Fink M
AD  - Technical University, Inffeldgasse 13, 8010 Graz, Austria; Research Center 
      Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria.
FAU - Llusa, Marcos
AU  - Llusa M
AD  - Research Center Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria.
FAU - Lawrence, Simon M
AU  - Lawrence SM
AD  - GlaxoSmithKline (GSK), New Frontiers Science Park, Harlow, Essex CM19 5AW, UK.
FAU - Biserni, Stefano
AU  - Biserni S
AD  - MG2, Via del Savena 18, I-40065, Pian di Macina di Pianoro, Bologna, Italy.
FAU - Calzolari, Vittorio
AU  - Calzolari V
AD  - MG2, Via del Savena 18, I-40065, Pian di Macina di Pianoro, Bologna, Italy.
FAU - Khinast, Johannes G
AU  - Khinast JG
AD  - Technical University, Inffeldgasse 13, 8010 Graz, Austria; Research Center 
      Pharmaceutical Engineering, Inffeldgasse 13, 8010 Graz, Austria. Electronic 
      address: khinast@tugraz.at.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140801
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Capsules)
RN  - 0 (Powders)
RN  - 3OWL53L36A (Mannitol)
RN  - J2B2A4N98G (Lactose)
SB  - IM
MH  - Administration, Inhalation
MH  - *Capsules
MH  - Lactose/chemistry
MH  - Mannitol/chemistry
MH  - Powders/*chemistry
MH  - Technology, Pharmaceutical/*methods
OTO - NOTNLM
OT  - Critical quality attributes
OT  - Dosator nozzle machine
OT  - Inhalation powders
OT  - Low-dose capsule filling
OT  - Low-fill weight
OT  - Multivariate data analysis
EDAT- 2014/08/05 06:00
MHDA- 2015/05/15 06:00
CRDT- 2014/08/05 06:00
PHST- 2014/06/20 00:00 [received]
PHST- 2014/07/23 00:00 [revised]
PHST- 2014/07/26 00:00 [accepted]
PHST- 2014/08/05 06:00 [entrez]
PHST- 2014/08/05 06:00 [pubmed]
PHST- 2015/05/15 06:00 [medline]
AID - S0378-5173(14)00549-3 [pii]
AID - 10.1016/j.ijpharm.2014.07.050 [doi]
PST - ppublish
SO  - Int J Pharm. 2014 Oct 1;473(1-2):617-26. doi: 10.1016/j.ijpharm.2014.07.050. Epub 
      2014 Aug 1.