An investigation into the influence of drug–polymer interactions on the miscibility, processability and structure of polyvinylpyrrolidone-based hot melt extrusion formulations

Chan, Siok-Yee; Qi, Sheng; Craig, Duncan Q.M.

doi:10.1016/j.ijpharm.2015.09.063

Cited by 40 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, the aged extrudates showed no drug melting event, indicating the absence of drug recrystallization after aging. Similar results were reported in the literature using paracetamol; however, upon extrusion temperatures above 120 °C [ 38 ].…”

Section: Resultssupporting

confidence: 90%

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products

et al. 2020

View full text Add to dashboard Cite

Here, we assessed the feasibility of hot-melt extrusion (HME) to obtain effervescent drug products for the first time. For this, a combined mixture design was employed using paracetamol as a model drug. Extrudates were obtained under reduced torque (up to 0.3 Nm) at 100 °C to preserve the stability of the effervescent salts. Formulations showed vigorous and rapid effervescent disintegration (<3 min), adequate flow characteristics, and complete solubilization of paracetamol instantly after the effervescent reaction. Formulations containing PVPVA in the concentration range of 15–20% m/m were demonstrated to be sensitive to accelerated aging conditions, undergoing marked microstructural changes, since the capture of water led to the agglomeration and loss of their functional characteristics. HPMC matrices, in contrast, proved to be resistant to storage conditions in high relative humidity, showing superior performance to controls, including the commercial product. Moreover, the combined mixture design allowed us to identify significant interactions between the polymeric materials and the disintegrating agents, showing the formulation regions in which the responses are kept within the required levels. In conclusion, this study demonstrates that HME can bring important benefits to the elaboration of effervescent drug products, simplifying the production process and obtaining formulations with improved characteristics, such as faster disintegration, higher drug solubilization, and better stability.

show abstract

Section: Resultssupporting

confidence: 90%

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products

et al. 2020

View full text Add to dashboard Cite

show abstract

“…drug-polymer system. Several research articles used this decrease of the melting temperature as an indicator of solid dosage forms polymer miscibility [59,60]. Mixing HPMC with PEG reduced the melting temperature of PEG from 24.7 to 6.3 • C (i.e.…”

Section: Mcc-pegmentioning

confidence: 99%

Polymer-plasticizer compatibility during coating formulation: A multi-scale investigation

Jarray

Gerbaud

Hémati

2016

Progress in Organic Coatings

View full text Add to dashboard Cite

During the formulation of solid dosage forms coating, plasticizers are added to the film forming polymer to improve the mechanical properties of the coating shell of the drug product. For the coating formulation to be successful and in order to produce flexible continuous film, the plasticizer should be compatible with the film forming polymer (i.e. high plasticizer-polymer miscibility in solid dispersion) (McGinity and Felton, 2008). This paper proposes and compares different multi-scale methods to predict the compatibility between plasticizers and film formers. The methods are based on, i) Molecule charge density using COSMO, ii) Solubility parameter calculation using Molecular dynamics, iii) Mesoscale simulation using DPD, where we propose a coarse-grain model, and iv) experimental DSC analysis for validation. The methods are tested for various blends including HPMC-PEG, MCC-PEG and PVP-PEG. The different methods showed similar results; PEG plasticizer diffuses inside HPMC and PVP polymer chains, thereby extending and softening the composite polymer. However, MCC surrounds PEG molecules without diffusing in its network, indicating low PEG-MCC compatibility. We also found that DPD simulations offer more details than the other methods on the miscibility between the compounds in aqueous solid dispersion, and can predict the amount of plasticizer that diffuse in the film forming polymer network.

show abstract

“…Fule et al [55] reported the feasibility of industrially manufacturing co-formulated extrudates using two model drugs in hydrophilic polymeric matrices. The use of theoretical and experimental drug-polymer interaction assessment with determination of processability and structures of dispersions in two polyvinylpyrrolidone-based polymers (PVP and PVP vinyl acetate, PVPVA) was highlighted by Chan et al [56]. Dong et al [57] reported a novel in situ synchrotron wide-angle X-ray diffraction (WAXD)-based approach to rapidly and accurately screen the formation of cocrystal and/or salts during heating inside an extruder barrel.…”

Section: Applications Via Hmementioning

confidence: 99%

Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters

Maniruzzaman

Nokhodchi

2017

Drug Discovery Today

View full text Add to dashboard Cite

A c c e p t e d M a n u s c r i p t Highlights  HME can be exploited in a broad range of applications for advanced drug delivery  Unique advantages to be utilised in a solvent free manufacturing platform  A means to explore the potential of continuous manufacture of pharmaceuticals  Scale-up issue considerations, from an FDA compliance point of view  HME regulatory guidelines for the manufacture of novel drug delivery systems Ali NokhodchiAli Nokhodchi is a professor of pharmaceutics and drug delivery at the University of Sussex. He has supervised over 120 Mpharm, PharmD, and MSc students and 15 PhD postgraduate students at several institutions in various fields of pharmaceutical formulations and drug delivery. He is an editorial board member of over 20 peer-reviewed international journals. Ali has published over 185 research articles in various fields of pharmaceutics, including tableting, particle engineering, inhalation, nanoparticles, dissolution, skin delivery, and controlled-release formulations. In addition, he has published five book chapters on skin, controlled-release formulations, particle engineering, and inhalation products. Ali has also been the editor of a book on pulmonary delivery published by Wiley in 2015. He has been the recipient of several prizes in pharmaceutical sciences and has been listed by Essential Science Indicators in the top 1% scientists in the field of pharmacology and toxicology.Currently, because globalization, the pharmaceutical industry is facing enormous challenges to comply with regulatory matters. Reduced patent life and overall decreased profitability of newly discovered drugs are also forcing the pharmaceutical industry to shorten the drug development time with maximum throughput. Therefore, continuous manufacturing (CM) processes via hot melt extrusion (HME) can be a promising alternative for achieving these goals. HME offers solvent-free green technology with a process that is easy to scale up. Moreover, CM provides better product quality assurance compared with batch processes, with fewer labor costs and shorter time to development. In this review, we primarily focus on various aspects of CM and the emerging application of HME to bridge the current manufacturing gap in pharmaceutical sphere.

show abstract

An investigation into the influence of drug–polymer interactions on the miscibility, processability and structure of polyvinylpyrrolidone-based hot melt extrusion formulations

Cited by 40 publications

References 34 publications

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products

Polymer-plasticizer compatibility during coating formulation: A multi-scale investigation

Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters

Contact Info

Product

Resources

About