Application of Quality by Design Approach for Hot-Melt Extrusion Process Optimization
01 Jan 2019-pp 209-228
TL;DR: In this article, the authors focused on the application of quality by design (QbD) on the process optimization of hot-melt extrusion (HME) to produce robust finished product.
Abstract: Hot-melt extrusion (HME) has emerged as a well-established industrial manufacturing technology in the pharmaceutical industry. There are a number of publications and patents on HME being used for the enhancement of solubility and bioavailability of poorly soluble drugs. The HME has been successfully used not only for solubility and dissolution rate enhancement but also for manufacturing various dosage forms such as granules, pellets, tablets, films, implants, suppositories, stents, depots, ophthalmic implants, and topical delivery systems. The processing parameters such as operating temperature, feed rate, screw speed, screw configuration, etc., has crucial role on the quality of final product. This chapter is focused on the application of quality by design (QbD) on the process optimization of HME to produce robust finished product. The knowledge of QbD and Process Analytical Technology (PAT) can be utilized to make HME as a continuous manufacturing process.
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TL;DR: This review has focused on the prediction of drug-polymer miscibility, the elements and sequence of QbD, and various screening and optimization designs, to provide insights into the formulation and process variables that are encountered routinely in the production of HME-based ASDs.
30 citations
TL;DR: In this article, a review of pharmaceutical approaches used to control and sustain drug release in oral formulations by Hot-Melt Extrusion (HME) and its combination with FDM 3D printing is presented.
14 citations
TL;DR: The ODFs of cyanocobalamin could be a better alternative formulation strategy for achieving rapid oral bioavailability in cobalamin deficiency.
9 citations
TL;DR: In this paper, the advantages and disadvantages of various cocrystal production methods including hot melt extrusion (HME) process are provided in the manuscript and an overview of the HME process and equipment, critical process parameters, and PAT for real-time monitoring of process has been reviewed in this article.
Abstract: Hot melt extrusion (HME) is emerging as a continuous, single-step, scalable, and industrially feasible process for the production of cocrystals. HME has gained momentum as a continuous and solvent-free process in the manufacturing of cocrystals. The incorporation of the matrix and the use of process analytical tool (PAT) for real-time monitoring further facilitate the process. The advantages and disadvantages of various cocrystal production methods including HME process are provided in the manuscript. Besides, an overview of the HME process and equipment, critical process parameters, and PAT for real-time monitoring of process has been reviewed in this article. Finally, recent literature related to the cocrystal synthesis via HME has been presented critically. This review provides useful information for the synthesis of the cocrystals using HME process.
6 citations
01 Jan 2021
TL;DR: In this paper, the hot-melt extrusion (HME) has emerged as one of the most versatile technologies to develop polymeric solid dispersions, and it has now displayed a holistic significance by introducing its potential to couple with modern technology such as 3D printing for personalized applications too.
Abstract: Over the last few decades, hot-melt extrusion (HME) has emerged as one of the most versatile technologies to develop polymeric solid dispersions. The overarching pharmaceutical applications of this technology has marked a significant impact mainly in the area of dissolution enhancement of poorly water-soluble drugs, taste masking of bitter active pharmaceutical ingredients (APIs), sustained and controlled release drug delivery, solid-state cocrystals, oral films, and most recently continuous manufacturing by embracing quality by design and process analytical technology. HME has now displayed a holistic significance by introducing its potential to couple with modern technology such as three-dimensional (3D) printing for personalized applications too. The advantage of coupling HME with a 3D printing technique has resulted in many publications and application notes recently. The process technology, advantages, formulation consideration and critical attributes, and wide-ranging pharmaceutical applications of HME will be critically surveyed in this chapter.
2 citations
References
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TL;DR: Improved bioavailability was achieved again demonstrating the value of the technology as a drug delivery tool, with particular advantages over solvent processes like co-precipitation.
790 citations
TL;DR: The Food and Drug Administration (FDA) regulates pharmaceutical drug products to ensure a continuous supply of high-quality drugs in the USA as mentioned in this paper, where the FDA supports the implementation of continuous manufacturing using science-and risk-based approaches.
Abstract: The Food and Drug Administration (FDA) regulates pharmaceutical drug products to ensure a continuous supply of high-quality drugs in the USA. Continuous processing has a great deal of potential to address issues of agility, flexibility, cost, and robustness in the development of pharmaceutical manufacturing processes. Over the past decade, there have been significant advancements in science and engineering to support the implementation of continuous pharmaceutical manufacturing. These investments along with the adoption of the quality-by-design (QbD) paradigm for pharmaceutical development and the advancement of process analytical technology (PAT) for designing, analyzing, and controlling manufacturing have progressed the scientific and regulatory readiness for continuous manufacturing. The FDA supports the implementation of continuous manufacturing using science- and risk-based approaches.
598 citations
TL;DR: This paper reviews the innumerable benefits of HME, based on a holistic perspective of the equipment, processing technologies to the materials, novel formulation design and developments, and its varied applications in oral drug delivery systems.
Abstract: Over the last three decades industrial adaptability has allowed hot-melt extrusion (HME) to gain wide acceptance and has already established its place in the broad spectrum of manufacturing operations and pharmaceutical research developments. HME has already been demonstrated as a robust, novel technique to make solid dispersions in order to provide time controlled, modified, extended, and targeted drug delivery resulting in improved bioavailability as well as taste masking of bitter active pharmaceutical ingredients (APIs). This paper reviews the innumerable benefits of HME, based on a holistic perspective of the equipment, processing technologies to the materials, novel formulation design and developments, and its varied applications in oral drug delivery systems.
243 citations
TL;DR: In this paper, hot-melt screw extrusion was presented as an alternative method for producing polymer-based sustained release (SFL) pellets, which were produced with diltiazem hydrochloride as model drug.
Abstract: Hot-melt screw extrusion was presented as an alternative method for producing polymer-based sustained release pellets. Special care was paid to the case of highly dosed freely soluble drugs which often pose technological problems with the usual manufacturing processes. In a preformulation study, polymers, plasticizers and drugs were selected according to various criteria including thermal stability. During these preliminary tests, the optimum extrusion conditions were defined. Four polymers were considered for extrusion trials, namely ethylcellulose, cellulose acetate butyrate, poly(ethylene-co-vinyl acetate) and a polymethacrylate derivative (Eudragit® RSPM). Pellets were produced with diltiazem hydrochloride as model drug. The surface appearance of various formulations was examined and the porosity assessed by means of mercury porosimetry. A distinct structure was found for the EVAC-based pellets. The overall porosity was less than 10%. Lastly, in vitro release of the drug showed a biphasic prof...
204 citations
TL;DR: Taste sensing technology demonstrated taste improvement for both polymers by correlating the data obtained for the placebo polymers and the pure APIs alone and the best masking effect was observed for VA64 at 30% PMOL loading.
152 citations