Melt extrusion: process to product

Repka, Michael A.; Shah, Sejal; Lu, Jingjing; Maddineni, Sindhuri; Morott, Joe; Patwardhan, Ketaki; Mohammed, Noorullah Naqvi

doi:10.1517/17425247.2012.642365

Cited by 126 publications

(97 citation statements)

References 83 publications

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“…Moreover, numerous aspects of the HME technology have been extensively cited in the literature. Additionally, the number of patents based on HME techniques has risen steadily worldwide in recent decades (4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

2015

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Abstract. Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

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Section: Introductionmentioning

confidence: 99%

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

2015

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“…A myriad of techniques such as spray drying [2], solvent evaporation [3], nanocrystal formation [4], complexation [5], and micronization of active pharmaceutical ingredient (API) [6] have been widely utilized in the industry to improve the solubility and/or dissolution rate of such BCS class II drugs, thereby enhancing their bioavailability. During the past couple of decades, hot-melt extrusion (HME) technology has gained enormous interest among researchers for improving the bioavailability of drug substances, especially those having low water solubility, by the formation of solid dispersions [7][8][9]. Compared to other techniques, HME offers several advantages such as being solvent-free, a potentially continuous process, and involving fewer processing steps in general.…”

Section: Introductionmentioning

confidence: 99%

Influence of Process and Formulation Parameters on Dissolution and Stability Characteristics of Kollidon® VA 64 Hot-Melt Extrudates

et al. 2014

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Abstract. The objective of the present study was to investigate the effects of processing variables and formulation factors on the characteristics of hot-melt extrudates containing a copolymer (Kollidon® VA 64). Nifedipine was used as a model drug in all of the extrudates. Differential scanning calorimetry (DSC) was utilized on the physical mixtures and melts of varying drug-polymer concentrations to study their miscibility. The drug-polymer binary mixtures were studied for powder flow, drug release, and physical and chemical stabilities. The effects of moisture absorption on the content uniformity of the extrudates were also studied. Processing the materials at lower barrel temperatures (115-135°C) and higher screw speeds (50-100 rpm) exhibited higher post-processing drug content (~99-100%). DSC and X-ray diffraction studies confirmed that melt extrusion of drug-polymer mixtures led to the formation of solid dispersions. Interestingly, the extrusion process also enhanced the powder flow characteristics, which occurred irrespective of the drug load (up to 40% w/w). Moreover, the content uniformity of the extrudates, unlike the physical mixtures, was not sensitive to the amount of moisture absorbed. The extrusion conditions did not influence drug release from the extrudates; however, release was greatly affected by the drug loading. Additionally, the drug release from the physical mixture of nifedipineKollidon® VA 64 was significantly different when compared to the corresponding extrudates (f 2 =36.70). The extrudates exhibited both physical and chemical stabilities throughout the period of study. Overall, hot-melt extrusion technology in combination with Kollidon® VA 64 produced extrudates capable of higher drug loading, with enhanced flow characteristics, and excellent stability.

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“…Hot-melt extrusion (HME) is a versatile processing technology that can be used for solubility enhancement, granulation, and as a physico-chemical stability imparting technology (14). Being a non-solvent process, HME has significant utility in the manufacture of solid dispersions and solid solutions.…”

Section: Introductionmentioning

confidence: 99%

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology

Mohammed¹,

Majumdar

Singh

et al. 2012

AAPS PharmSciTech

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Abstract. The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.

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Melt extrusion: process to product

Abstract: Interest in HME as a pharmaceutical process continues to grow and the potential of automation and reduction of capital investment and labor costs has earned this technique a necessary consideration as a drug delivery solution.

Cited by 126 publications

References 83 publications

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

Influence of Process and Formulation Parameters on Dissolution and Stability Characteristics of Kollidon® VA 64 Hot-Melt Extrudates

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology

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