Continuous twin-screw granulation for enhancing the dissolution of poorly water soluble drug

Maniruzzaman, Mohammed; Nair, Arun K.; Renault, Maxcene; Nandi, Uttom; Scoutaris, Nikolaos; Farnish, Richard; Bradley, M.S.A.; Snowden, Martin J.; Douroumis, Dennis

doi:10.1016/j.ijpharm.2015.09.025

Cited by 26 publications

(20 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is because, in order to increase the apparent solubility and the dissolution rate of the solid state-limited compounds, the strong crystal lattice has to be weakened. This can be achieved by using another polymorph (44), by introduction of co-formers to produce co-crystals (45,46), by selecting a salt of the drug (47), by making use of prodrug strategies (48), nanocrystal technologies (49,50) or by using amorphization (or formation of amorphous nanoparticles) (51–53). For a long period, amorphization was not the first choice because of the inherent instability issues resulting from the high energy form of the amorphous solid material (as indicated in the Background section).…”

Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

2017

View full text Add to dashboard Cite

The alarming numbers of poorly soluble discovery compounds have centered the efforts towards finding strategies to improve the solubility. One of the attractive approaches to enhance solubility is via amorphization despite the stability issue associated with it. Although the number of amorphous-based research reports has increased tremendously after year 2000, little is known on the current research practice in designing amorphous formulation and how it has changed after the concept of solid dispersion was first introduced decades ago. In this review we try to answer the following questions: What model compounds and excipients have been used in amorphous-based research? How were these two components selected and prepared? What methods have been used to assess the performance of amorphous formulation? What methodology have evolved and/or been standardized since amorphous-based formulation was first introduced and to what extent have we embraced on new methods? Is the extent of research mirrored in the number of marketed amorphous drug products? We have summarized the history and evolution of amorphous formulation and discuss the current status of amorphous formulation-related research practice. We also explore the potential uses of old experimental methods and how they can be used in tandem with computational tools in designing amorphous formulation more efficiently than the traditional trial-and-error approach.

show abstract

Section: Current Status Of Research On Amorphous Formulationsmentioning

confidence: 99%

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

2017

View full text Add to dashboard Cite

show abstract

“…In such systems a crystalline drug is covered into amorphous form or a molecularly dispersed system is formed [4]. In recent years combinatorial chemistry and high throughput screening has resulted into rise in the number of poorly water soluble drugs found in pharmaceutical discovery pipeline [5]. Sufficient aqueous solubility and bioavailability is needed for optimum oral absorption of a drug candidate.…”

Section: Introductionmentioning

confidence: 99%

Study the influence of formulation process parameters on solubility and dissolution enhancement of efavirenz solid solutions prepared by hot-melt extrusion: a QbD methodology

Pawar

Suryawanshi

Moravkar

et al. 2018

Drug Deliv. and Transl. Res.

Self Cite

View full text Add to dashboard Cite

The current study investigates the dissolution rate performance of amorphous solid solutions of a poorly water-soluble drug, efavirenz (EFV), in amorphous Soluplus® (SOL) and Kollidon® VA 64 (KVA64) polymeric systems. For the purpose of the study, various formulations with varying drug loadings of 30, 50, and 70% w/w were developed via hot-melt extrusion processing and adopting a Box-Behnken design of experiment (DoE) approach. The polymers were selected based on the Hansen solubility parameter calculation and the prediction of the possible drug-polymer miscibility. In DoE experiments, a Box-Behnken factorial design was conducted to evaluate the effect of independent variables such as Soluplus® ratio (A), HME screw speed (A), and processing temperature (A), and Kollidon®VA64 ratio (B), screw speed (B), and processing temperature (B) on responses such as solubility (X and Y) and dissolution rate (X and Y) for both ASS [EFV:SOL] and BSS [EFV:KVA64] systems. DSC and XRD data confirmed that bulk crystalline EFV transformed to amorphous form during the HME processing. Advanced chemical analyses conducted via 2D COSY NMR, FTIR chemical imaging, AFM analysis, and FTIR showed that EFV was homogenously dispersed in the respective polymer matrices. The maximum solubility and dissolution rate was observed in formulations containing 30% EFV with both SOL and KVA64 alone. This could be attributed to the maximum drug-polymer miscibility in the optimized formulations. The actual and predicted values of both responses were found precise and close to each other.

show abstract

“…In a second report, the same group reported a novel case of utilizing a twin-screw granulator for the enhancement of the dissolution rate of the poorly water-soluble drug ibuprofen, as depicted in Figure 4 [62]. Similarly, a novel granulation process was exploited by Sayin et al [63] by using an 11-mm twin-screw HME machine.…”

Section: Applications Via Hmementioning

confidence: 99%

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

Maniruzzaman

Nokhodchi

2017

Drug Discovery Today

Self Cite

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

Continuous twin-screw granulation for enhancing the dissolution of poorly water soluble drug

Cited by 26 publications

References 27 publications

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

Study the influence of formulation process parameters on solubility and dissolution enhancement of efavirenz solid solutions prepared by hot-melt extrusion: a QbD methodology

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

Contact Info

Product

Resources

About