A Review of Hot Melt Extrusion Process Technology to

Pharmaceutical Products
1. Introduction
Up to now HME has emerged while a novel processing technology found in growing molecular
dispersions of active pharmaceutical elements (APIs) into various polymer or/and lipid matrices
which includes led this approach to demonstrate period controlled, modified, extended, and targeted
medication delivery [1-4]. HME has now provided opportunity for use of materials in order to mask
the bitter taste of active substances. Since the industrial program of the extrusion process back in
the 1930s, HME has received considerable interest from both pharmaceutical industry and
academia in a variety of applications for pharmaceutical dosage forms, such as tablets, capsules,
movies, and implants for medicine delivery via oral, transdermal, and transmucosal routes [5]. This
makes HME an excellent option to other conventionally obtainable techniques such as roll spinning
and spray drying. Not only is it a proven manufacturing process, HME meets the goal of the united
states Food and Medication Administrations (FDA) method analytical technology (PAT) scheme for
designing, analyzing, and controlling the developing process via quality control measurements
during energetic extrusion method [6]. In this chapter, the hot-melt extrusion approach is reviewed
predicated on a holistic perspective of its various ingredients, processing technologies, and the
supplies and novel formulation style and advancements in its varied applications in oral medication
delivery systems.
2. Method Technology of Hot-Melt Extrusion (HME)
Hot-melt extrusion approach was first invented for the making of lead pipes at the end of the
eighteenth century [7]. Since then, it has been found in the plastic material, rubber, and meals
manufacturing industry to create items which range from pipes to bedding and bags. With the
introduction of big throughput screening, more than half of all plastic products including luggage
currently, bed sheets, and pipes are created my HME and therefore various polymers have already
been utilized to melt and type different shapes for a variety of commercial and domestic
applications. The technology (HME) has shown to be a robust method of producing numerous
medicine delivery systems and for that reason it has been found to become beneficial in the
pharmaceutical sector aswell [8]. Extrusion is the process of pumping recycleables at elevated
controlled heat range and pressure through a heated barrel into a product of uniform condition and
density [9]. Breitenbach first introduced the production of melt extrusion procedure in
pharmaceutical manufacturing operations [10]; nevertheless, Follonier and his coworkers first of all
examined the hot-melt technology to produce sustained release polymer-based pellets of varied
freely soluble drugs [11]. HME involves the compaction and transformation of blends from a powder
or a granular mix into a item of uniform shape [9]. In this process, polymers are melted and
produced into items of different sizes and shapes such as for example plastic bags, bedding, and
pipes by forcing polymeric components and active substances incorporating any additives or
plasticisers through an orifice or die under controlled temperature, pressure, feeding rate, and
screw speed [9, 12]. However, the theoretical approach to understanding the melt extrusion
procedure (Figure 1) could be summarized by classifying the complete process of HME compaction
into the following [13]:(1)feeding of the extruder through a hopper,(2)mixing, grinding, lowering the
particle size, venting, and kneading,(3)move through the die, and(4)extrusion from the die and
further downstream processing.
Number 1: Schematic diagram of the HME process [12].

The extruder generally consists of a couple of rotating screws (either corotating or counter rotating)
in the stationary cylindrical barrel. The barrel can be often stated in sections to be able to shorten
the residence time of molten resources. The sectioned parts of the barrel are then bolted or clamped
in concert. An end-plate die can be connected to the finish of the barrel that is determined based on
the form of the extruded materials.
3. Twin-Screw and single-screw Extruder
A single-screw extruder consists of one rotating screw positioned inside a stationary barrel at most
fundamental level. In the more complex twin-screw systems, extrusion of materials is conducted by
either a counter-rotating or corotating screw configuration [9]. Regardless of type and complexity of
the function and process, the extruder must be with the capacity of rotating the screw at a
determined predetermined quickness while compensating for the torque and shear plastic recycling
extruder machine generated from both material staying extruded and the screws used. However,
whatever the size and type of the screw in the stationary barrel an average extrusion set up includes
a motor which functions as a drive device, an extrusion barrel, a rotating screw, and an extrusion die
[13]. A central electric control unit is connected to the extrusion unit as a way to control the
procedure parameters such as for example screw speed, temp, and pressure [14] therefore. This
electronic control unit works as a monitoring system as well. The normal length size ratios (L/D) of
screws positioned in the stationary barrel are another essential characteristic to consider whether
the extrusion products is a single-screw or twin-screw extruder. The L/D of the screw either in a
single-screw extruder or a twin-screw extruder typically ranges from 20 to 40?:?1 (mm). In the event
of the application of pilot plant extruders the diameters of the screws substantially ranges from 18 to
30?mm. In pharmaceutical scale up, the production machines are much bigger with diameters
exceeding 50-60 typically?mm [15]. In addition, the measurements of a screw modification over the
amount of the barrel. In probably the most advanced processing machines for extrusion, the screws
could be separated by clamps or become extended in proportion to along the barrel itself. A simple
single-screw extruder consists of three discrete zones: feed zone, compression, and a metering area
(Figure 2). Under the compression zone that is basically known as processing zone could be
accompanied by few other simple steps such as mixing, kneading, and venting [13, 15].
Number 2: Schematic diagram of a single-screw extruder [10].
The depth together with the pitch of the screw flights (both perpendicular and axial) differ within
each zone, generating dissimilar pressures across the screw size (Figure 3). Normally the pressure
within the feed area is quite low in order to allow for reliable feeding from the hopper and soft
combining of API, polymers, and additional excipients and therefore the screw airline flight depth
and pitch happen to be kept bigger than that of additional zones. At this stage of the process the
pressure within the extruder is very low which subsequently gets heightened in the compression
zone. This process outcomes in a gradual upsurge in pressure along the amount of the compression
zone, which properly imparts a high amount of mixing and compression to the materials (by
reducing the screw pitch and/or the trip depth) [9, 15]. Additionally the major goal of the
compression zone is not only to homogenize but as well compress the extrudate to guarantee the
molten material reaches the final section of the barrel (metering zone) in an application befitting
processing. Finally the final section which is known as the metering area stabilizes the effervescent
flow of the matrix and ensures the extruded item includes a uniform thickness, shape, and size. A
consistent and regular uniform screw airline flight depth and pitch helps to maintain continuous
high pressure ensuring a uniform delivery price of extrudates through the extrusion die and hence a
uniform extruded merchandise.
Number 3: Screw geometry (extrusion) [9].

In addition to the above-mentioned devices, downstream auxiliary appliances for cooling, cutting,
and collecting the finished merchandise is also typically employed. Mass stream feeders to
accurately meter materials in to the feed hopper, pelletizers, spheronizer, roller/calendaring device
in order to produce continuous films, and procedure analytical technology such as near infrared
(NIR) and Raman, ultrasound, and DSC systems are also options. Through the entire whole process,
the temperature in all zones is normally controlled by electrical heating bands and monitored by
thermocouples.
The single-screw extrusion system is simple and offers plenty of advantages but even now does not
acquire the combining capacity for a twin-screw machine and for that reason is not the most wellliked approach for the production of most pharmaceutical formulations. In addition, a twin-screw
extruder gives much greater versatility (procedure manipulation and optimisation) in
accommodating a wider selection of pharmaceutical formulations making this setup much more
constructive. The rotation of the screws in the extruder barrel may either come to be corotating
(same way) or counter-rotating (opposite direction), both directions being equivalent from a
processing perspective (Figure 4). A greater level of conveying and much shorter residence times
happen to be achievable with an intermeshing setup. Furthermore, using reverse-conveying and
forward-conveying factors, kneading blocks, and other intricate patterns as a means of improving or
managing the amount of mixing required might help the configuration of the screws themselves to
become varied [16].
Figure 4: A good twin-screw extruder and screws [9].
4. Advantages and Disadvantages of HME
HME offers several advantages over conventionally available pharmaceutical processing methods
including (a good) increased solubility and bioavailability of normal water insoluble substances; (b)
solvent-free nonambient procedure; (c) economical method with reduced production time, fewer
processing measures, and a continuous operation; (d) functions of sustained, altered, and targeted
release; (e) better articles uniformity in extrudates; (f) no requirements for the compressibility of
active ingredients; (g) uniform dispersion of fine particles; (h) good balance at changing pH and
moisture levels and safe software in humans; (i) reduced amount of unit operations and production
of an array of performance dosage forms (j) a variety of screw geometries [17-21].
However, HME has some disadvantages as well. The main drawbacks of HME contain thermal
process (drug/polymer stability), use of a limited amount of polymers, high stream properties of
polymers, and excipients required rather than suitable for relatively high heat sensitive molecules
such as for example microbial species and proteins