Continuous manufacturing of solid lipid nanoparticles by hot melt extrusion

Patil, Hemlata; Kulkarni, Vijay; Majumdar, Soumyajit; Repka, Michael A.

doi:10.1016/j.ijpharm.2014.05.024

Cited by 50 publications

(26 citation statements)

References 10 publications

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“…Ishikawa diagram (also known as fish-bone diagrams or cause-and- . Screw configuration and mixing zones used in the preparation of SLN by HME [8] effect diagrams) was constructed to identify the potential risks, and corresponding causes were created to identify quality attributes for the better performance of developed FBT SLN by HME-HPH technique (see supplementary data Fig. 1).…”

Section: Preliminary Studymentioning

confidence: 99%

“…The solvent-based technique utilizes organic solvents to dissolve the solid lipid; the solvent is then evaporated from the emulsion to obtain SLN. In the non-solvent technique, the solid lipid is liquefied over its melting point and is subsequently converted to nanoemulsions through common techniques such as high-pressure homogenization, in which cooling further results in SLN [8].…”

Section: Introductionmentioning

confidence: 99%

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Continuous Production of Fenofibrate Solid Lipid Nanoparticles by Hot-Melt Extrusion Technology: a Systematic Study Based on a Quality by Design Approach

Patil

Feng

et al. 2014

AAPS J

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Abstract. This contribution describes a continuous process for the production of solid lipid nanoparticles (SLN) as drug-carrier systems via hot-melt extrusion (HME). Presently, HME technology has not been used for the manufacturing of SLN. Generally, SLN are prepared as a batch process, which is time consuming and may result in variability of end-product quality attributes. In this study, using Quality by Design (QbD) principles, we were able to achieve continuous production of SLN by combining two processes: HME technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. Fenofibrate (FBT), a poorly water-soluble model drug, was incorporated into SLN using HME-HPH methods. The developed novel platform demonstrated better process control and size reduction compared to the conventional process of hot homogenization (batch process). Varying the process parameters enabled the production of SLN below 200 nm. The dissolution profile of the FBT SLN prepared by the novel HME-HPH method was faster than that of the crude FBT and a micronized marketed FBT formulation. At the end of a 5-h in vitro dissolution study, a SLN formulation released 92-93% of drug, whereas drug release was approximately 65 and 45% for the marketed micronized formulation and crude drug, respectively. Also, pharmacokinetic study results demonstrated a statistical increase in Cmax, Tmax, and AUC 0-24 h in the rate of drug absorption from SLN formulations as compared to the crude drug and marketed micronized formulation. In summary, the present study demonstrated the potential use of hot-melt extrusion technology for continuous and large-scale production of SLN.

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Section: Preliminary Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Continuous Production of Fenofibrate Solid Lipid Nanoparticles by Hot-Melt Extrusion Technology: a Systematic Study Based on a Quality by Design Approach

Patil

Feng

et al. 2014

AAPS J

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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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“…A modified screw design as shown in Fig. 2, with 3 mixing zones, was used for extrusion (12,13). The composition of the ointments is shown in Table I.…”

Section: Preparation Of Ointment Formulationmentioning

confidence: 99%

Development of an Ointment Formulation Using Hot-Melt Extrusion Technology

et al. 2015

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Abstract. Ointments are generally prepared either by fusion or by levigation methods. The current study proposes the use of hot-melt extrusion (HME) processing for the preparation of a polyethylene glycol base ointment. Lidocaine was used as a model drug. A modified screw design was used in this process, and parameters such as feeding rate, barrel temperature, and screw speed were optimized to obtain a uniform product. The product characteristics were compared with an ointment of similar composition prepared by conventional fusion method. The rheological properties, drug release profile, and texture characteristics of the hot-melt extruded product were similar to the conventionally prepared product. This study demonstrates a novel application of the hotmelt extrusion process in the manufacturing of topical semi-solids.

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Continuous manufacturing of solid lipid nanoparticles by hot melt extrusion

Cited by 50 publications

References 10 publications

Continuous Production of Fenofibrate Solid Lipid Nanoparticles by Hot-Melt Extrusion Technology: a Systematic Study Based on a Quality by Design Approach

Continuous Production of Fenofibrate Solid Lipid Nanoparticles by Hot-Melt Extrusion Technology: a Systematic Study Based on a Quality by Design Approach

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

Development of an Ointment Formulation Using Hot-Melt Extrusion Technology

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