Abstract:
:Streamlining the manufacturing process has been recognized as a key issue to reduce production costs and improve safety in pharmaceutical manufacturing. Although data available from earlier developmental stages are often sparse and unstructured, they can be very useful to improve the understanding about the process under development. In this paper, a general procedure is proposed for the application of latent variable statistical methods to support the development of new continuous processes in the presence of limited experimental data. The proposed procedure is tested on an industrial case study concerning the development of a continuous line for the manufacturing of paracetamol tablets. The main driving forces acting on the process are identified and ranked according to their importance in explaining the variability in the available data. This improves the understanding about the process by elucidating how different active pharmaceutical ingredient pretreatments, different formulation modes and different settings on the processing units affect the overall operation as well as the properties of the intermediate and final products. The results can be used as a starting point to perform a comprehensive and science-based quality risk assessment that help to define a robust control strategy, possibly enhanced with the integration of a design space for the continuous process at a later stage.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Tomba E,De Martin M,Facco P,Robertson J,Zomer S,Bezzo F,Barolo Mdoi
10.1016/j.ijpharm.2013.01.018subject
Has Abstractpub_date
2013-02-28 00:00:00pages
25-39issue
1-2eissn
0378-5173issn
1873-3476pii
S0378-5173(13)00034-3journal_volume
444pub_type
杂志文章abstract::Surface functionalisation of polymeric electrospun scaffolds with therapeutic biomolecules is often explored in regenerative medicine and tissue engineering. However, the bioconjugation method must be carefully selected to prevent partial or full loss of activity of the biomolecule following chemical manipulation. Per...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2021.120231
更新日期:2021-01-20 00:00:00
abstract::Effects of pH and co-solvents on the bio-mimetic artificial membrane permeation assay were investigated to determine the optimal conditions for the prediction of oral absorption. The permeability (P(am)) of 33 structurally diverse drugs to the PC/PE/PS/PI/CHO/1,7-octadiene membrane system (bio-mimetic lipid (BML) memb...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(01)00845-6
更新日期:2001-10-09 00:00:00
abstract::Physical and chemical structure of paclitaxel (PTX) was studied after its incorporation into polymeric micelles made of hyaluronic acid (HA) (Mw=15 kDa) grafted with C6 or C18:1 acyl chains. PTX was physically incorporated into the micellar core by solvent evaporation technique. Maximum loading capacity for HAC6 and H...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2014.03.024
更新日期:2014-05-15 00:00:00
abstract::A highly accurate nephelometric titration for the determination of promethazine hydrochloride and its preparations was presented. The titration operating conditions were studied and the solubility product constant of promethazine tetraphenylboron precipitation was determined. The result of the titration is comparable ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2005.05.043
更新日期:2005-09-30 00:00:00
abstract::Viscous liquid degradable polymers have advantages as drug depots for sustained protein delivery. We have created a new aliphatic polycarbonate for this purpose, poly(trimethylene carbonate-co-5-hydroxy trimethylene carbonate), which upon degradation retains a near neutral micro-environmental pH. As such, this copolym...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2020.119965
更新日期:2020-11-30 00:00:00
abstract::This study focuses on evaluating the potential of transferring from a batch process to continuous process for manufacturing of the extended release formulation. Metformin hydrochloride (HCl) was used in the model formulation which was intended to contain the high amount of hydrophilic drug. The effects of barrel tempe...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2017.07.019
更新日期:2017-08-30 00:00:00
abstract::In the present study, a novel synthesis technique based on the flow focusing (FF) technology is investigated for the preparation of green fluorescent protein (GFP)-loaded poly(D,L-lactide-co-glycolide) (PLGA) microparticles. To our knowledge, this novel technique has never been applied to the formulation of proteins i...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2009.07.017
更新日期:2009-10-01 00:00:00
abstract::The self-organizing complexes with hyaluronic acid (HA) and polydopamine (PDA), an adhesion mediator via hydrogen bonding, were investigated for use as protein drug carriers. The complexes were prepared with HA of different molecular weights (20 kDa and 200 kDa) and various molar ratios of dopamine and lysozyme, a mod...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.03.007
更新日期:2018-05-05 00:00:00
abstract::An understanding of the action of many drugs requires a knowledge of how the drug reaches the site of action in a cell. A detailed knowledge of the structure and function of cell membranes is often required to understand the transport of drugs across the plasma membrane. To obtain this information proteins must be iso...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,评审
doi:10.1016/s0378-5173(98)00345-7
更新日期:1999-01-25 00:00:00
abstract::Liposomal formulations were made using Solvent-assisted active loading technology (SALT). Two formulations composed of HSPC:DPPG:Chol:DSPE-mPEG2000 (PG-LipCUR) and HSPC:Chol:DSPE-mPEG2000 (LipCUR) demonstrated good colloidal properties and the CUR-encapsulation of 82% and 89% for PG-LipCUR and LipCUR, respectively. Th...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2020.119211
更新日期:2020-04-30 00:00:00
abstract::Understanding mechanical properties of pharmaceutical solids at the submicron scale can be very important to pharmaceutical research & development. In this paper, the hardness of individual particles of various pharmaceutical solids including sucrose, lactose, ascorbic acid, and ibuprofen was quantified using the atom...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2008.06.015
更新日期:2008-10-01 00:00:00
abstract::An increased number of amorphous formulations of poorly water soluble drugs are being introduced into the market due to their higher transient solubility and thus faster absorption and higher bioavailability. While most amorphous drug products contain a single drug substance, there is a growing trend towards co-formul...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.10.026
更新日期:2015-12-30 00:00:00
abstract::The current investigation was carried out to identify appropriate parameters for measuring the in vitro release of tobramycin (TOB) ophthalmic ointments and to evaluate the feasibility of in vitro release testing methods to assess the product performance. Drug release was assessed using USP dissolution apparatus IV an...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2020.119938
更新日期:2020-11-30 00:00:00
abstract::Nicotinic acid was grafted on (poly(ɛ-caprolactone))(2)-poly(ethylene glycol) copolymers that were used for the preparation of nanoparticles with the objectives to monitor particle size and to optimize the drug loading capacity as well as the release profile of the particles. Increasing amounts of grafting nicotinic a...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2011.11.033
更新日期:2012-02-28 00:00:00
abstract::Organic solvent extraction/evaporation from an o/w-dispersion has been widely used for the fabrication of PLGA microparticles. The purpose of this work was to elucidate the kinetics of the solvent extraction/evaporation process. A mathematical diffusion model was developed and applied to predict the duration of the so...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2008.08.015
更新日期:2008-11-19 00:00:00
abstract::Prostaglandin E(1) (PGE1) shows various pharmacological activities including anti-inflammation. However, the rapid metabolization and inactivation of the intravenously administered PGE1 during the first passage through the lungs result in significant non-compliance in clinical trials which greatly limits its applicati...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2009.12.019
更新日期:2010-03-15 00:00:00
abstract::The aim of the present work was to characterize in vitro sumatriptan transdermal absorption through human skin and to investigate the effect of chemical enhancers and iontophoresis applied both individually and in combination. A secondary objective was to compare the results obtained with those in porcine skin under t...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2006.05.049
更新日期:2006-10-12 00:00:00
abstract::The role of the newly discovered cysteine protease, cathepsin K, in osteoporosis and rheumatoid arthritis is reviewed. The current development of cathepsin K inhibitors and their targeted delivery using synthetic polymer carriers are discussed. Future challenges and possible strategies to improve these delivery system...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,评审
doi:10.1016/j.ijpharm.2003.03.003
更新日期:2004-06-11 00:00:00
abstract::Superparamganetic iron oxide-based contrast agents in magnetic resonance imaging (MRI) have offered new possibility for early detection of lymph nodes and their metastases. According to important role of nanoparticle size in biodistribution, magnetite nanoparticles coated with different polyethylene glycol (PEG) conce...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2012.04.080
更新日期:2012-08-20 00:00:00
abstract::NLC topical formulation as an alternative to oral and parenteral (IM) delivery of artemether (ART), a poorly water-soluble drug was designed. A Phospholipon 85G-modified Gelucire 43/01 based NLC formulation containing 75% Transcutol was chosen from DSC studies and loaded with gradient concentration of ART (100-750 mg)...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2014.10.004
更新日期:2014-12-30 00:00:00
abstract::This work was aimed at assessing the preparation and characteristics of "dextran-magnetic layered double hydroxide-fluorouracil" liposomes (DMFL). DMFL was prepared by the optimized reverse evaporation method, which concerned the entrapment efficiency and slow-released effect. The factors affecting the entrapment effi...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2013.04.010
更新日期:2013-06-25 00:00:00
abstract::Many medicines prescribed for children are unlicensed. Solid dosage forms present problems as children have difficulty swallowing whole tablets or capsules. When medicines are not licensed for children, it is unlikely that there will be a suitable, licensed liquid formulation and so extemporaneous liquid preparations ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2005.05.006
更新日期:2005-08-26 00:00:00
abstract::The encapsulation of lipophilic drugs in polymeric nanoparticles can form simultaneously both polymeric nanoparticles and drug nanocrystals. The objective was to detect the presence of nanocrystals in the nanoparticle suspensions using a simple methodology, and to determine if the nanocrystals are formed during prepar...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2008.04.007
更新日期:2008-07-09 00:00:00
abstract::Rifampicin is a first-line, highly effective drug currently used orally as a part of a lengthy multi-drug regimen against tuberculosis (TB). Despite the potential of inhaled therapy as an effective approach for TB treatment, an inhalable formulation of rifampicin has not yet been developed for clinical use. In order t...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2020.119602
更新日期:2020-09-25 00:00:00
abstract::Proquazone, a poorly wettable compound, was used as a model drug in the search for reasons to develop a capsule or tablet formulation. The capsules were filled with proquazone as active ingredient, with lactose monohydrate (200 mesh) as filler and with magnesium stearate as lubricant. The tablet was made out of a gran...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2004.09.006
更新日期:2004-12-09 00:00:00
abstract::The objective of this study was to evaluate the combination of pH-dependent and time-dependent polymers as a single coating for design of colon delivery system of indomethacin pellets. Eudragit S100 and Eudragit L100 were used as pH-dependent polymers and Eudragit RS was used as a time-dependent polymer. A statistical...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2006.05.011
更新日期:2006-08-31 00:00:00
abstract::The objective of this study was to investigate the integrtity and stability of oral liposomes containing glycocholate (SGC-Lip) in simulated gastrointestinal (GI) media and ex vivo GI media from rats in comparison with conventional liposomes (CH-Lip) composed of soybean phosphatidylcholine and cholesterol. Membrane in...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2012.10.025
更新日期:2013-01-30 00:00:00
abstract::It is well acknowledged that oral bioavailability of a drug candidate is often influenced by factors such as the permeability, physico-chemical properties, and metabolism of the drug. Among the physico-chemical properties, solubility and dissolution rate are considered the most critical factors affecting the oral bioa...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2013.06.064
更新日期:2013-09-15 00:00:00
abstract::A series of new, low molecular mass, lysine-based peptide dendrimers with varying distribution of cationic and aromatic groups in the structure were synthesized. They expressed antimicrobial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria as well as against fungal p...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2005.10.039
更新日期:2006-02-17 00:00:00
abstract::The ionization and transport properties of lidocaine hydrochloride (LidHCl) in aqueous propylene glycol (PG) containing 20% PG by weight was studied by means of electrical precision conductometry. For drug concentrations exceeding about 1.7 mM a slight formation of LidH(+)Cl(-) ion-pairs is indicated; ion-pair associa...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(00)00400-2
更新日期:2000-05-15 00:00:00