A Review of Hot Melt Extrusion Process Technology to

Pharmaceutical Products
1. Introduction
To date HME has emerged while a novel processing technology in developing molecular dispersions
of dynamic pharmaceutical elements (APIs) into various polymer or perhaps/and lipid matrices which
includes led this approach to demonstrate period controlled, modified, extended, and targeted drug
delivery [1-4]. HME has provided opportunity for usage of materials in order to mask the bitter taste
of active substances. Because the industrial application of the extrusion procedure back the 1930s,
HME has received considerable attention from both pharmaceutical industry and academia in a
range of applications for pharmaceutical dosage forms, such as tablets, capsules, films, and implants
for medication delivery via oral, transdermal, and transmucosal routes [5]. This makes HME a
fantastic option to other available techniques such as for example roll spinning and spray drying
conventionally. Not only is it a proven manufacturing method, HME meets the goal of the united
states Food and Medication Administrations (FDA) method analytical technology (PAT) scheme for
designing, examining, and controlling the manufacturing process via top quality control
measurements during dynamic extrusion process [6]. In this chapter, the hot-melt extrusion
approach is reviewed based on a holistic point of view of its various components, processing
technologies, and the supplies and novel formulation style and developments in its varied
applications in oral medicine delivery systems.
2. Process Technology of Hot-Melt Extrusion (HME)
Hot-melt extrusion technique was initially invented for the making of lead pipes towards the end of
the eighteenth century [7]. Since that time, it has been found in the plastic, rubber, and food
production industry to create items which range from pipes to bags and linens. With the arrival of
large throughput screening, currently over fifty percent of all plastic products including carriers,
linens, and pipes are developed my HME and for that reason various polymers have been utilized to
melt and form different shapes for a variety of industrial and domestic applications. The technology
(HME) has shown to be a robust approach to producing numerous medication delivery systems and
therefore it has been found to come to be valuable in the pharmaceutical industry as well [8].
Extrusion is the procedure for pumping raw materials at elevated controlled temp and pressure
through a heated barrel right into a product of uniform form and density [9]. Breitenbach first
introduced the development of melt extrusion process in pharmaceutical manufacturing operations
[10]; even so, Follonier and his coworkers 1st examined the hot-melt technology to produce
sustained let go polymer-based pellets of varied freely soluble drugs [11]. HME includes the
compaction and alteration of blends from a powder or a granular mix right into a merchandise of
uniform shape [9]. In this process, polymers are melted and formed into items of different shapes
and sizes such as plastic bags, bed sheets, and pipes by forcing polymeric elements and active
substances incorporating any additives or plasticisers through an orifice or die under managed
temperature, pressure, feeding cost, and screw speed [9, 12]. Even so, the theoretical approach to
understanding the melt extrusion process (Figure 1) could be summarized by classifying the
complete treatment of HME compaction in to the following [13]:(1)feeding of the extruder through a
hopper,(2)mixing, grinding, lowering the particle size, venting, and kneading,(3)flow through the
die, and(4)extrusion from the die and further downstream processing.
Shape 1: Schematic diagram of the HME process [12].

The extruder generally includes one or two rotating screws (either corotating or counter rotating)
inside a stationary cylindrical barrel. The barrel is undoubtedly often manufactured in sections in
order to shorten the home time of molten substances. The sectioned parts of the barrel are then
bolted or clamped jointly. An end-plate die is normally linked to the end of the barrel that is
determined in line with the shape of the extruded materials.
3. Twin-Screw and single-screw Extruder
A single-screw extruder includes 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
the counter-rotating or corotating screw configuration [9]. Regardless of complexity and type of the
function and method, the extruder must be capable of rotating the screw at a determined
predetermined swiftness while compensating for the torque and shear generated from both material
becoming extruded and the screws used. However, whatever the size and type of the screw in the
stationary barrel a typical extrusion set up consists of a motor which works as a drive unit, an
extrusion barrel, a rotating screw, and an extrusion die [13]. A central electronic control unit is
connected to the extrusion product in order to control the process parameters such as screw speed,
heat range, and therefore pressure [14]. This electronic control product functions as a monitoring
equipment as well. The normal length diameter ratios (L/D) of screws positioned in the stationary
barrel are another essential characteristic to consider whether the extrusion apparatus is a singlescrew 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 case of the application of pilot plant extruders
the diameters of the screws significantly ranges from 18 to 30?mm. In pharmaceutical scale up, the
creation machines are much larger with diameters commonly exceeding 50-60?mm [15]. In addition,
the measurements of a screw change over the length of the barrel. In probably the most advanced
processing tools for extrusion, the screws could possibly be separated by clamps or be extended in
proportion to along the barrel itself. A basic single-screw extruder includes three discrete zones:
feed area, compression, and a metering zone (Figure 2). Beneath the compression zone which is
basically referred to as processing zone could be associated with few other steps such as combining,
kneading, and venting [13, 15].
Physique 2: Schematic diagram of a single-screw extruder [10].
The depth combined with the pitch of the screw flights (both perpendicular and axial) differ within
each area, generating dissimilar pressures along the screw size (Figure 3). Normally the pressure
within the feed zone is quite low in order to allow for reliable feeding from the hopper and soft
mixing of API, polymers, and various other excipients and then the screw airline flight depth and
pitch will be kept bigger than that of other zones. At this time of the process the pressure within the
extruder is quite low which subsequently gets raised in the compression area. This process effects in
a gradual increase in pressure along the amount of the compression area, which effectively imparts
a high amount of combining and compression to the material (by decreasing the screw pitch and/or
the trip depth) [9, 15]. Furthermore the major aim of the compression zone isn't only to homogenize
but also compress the extrudate to guarantee the molten material reaches the final section of the
barrel (metering zone) in plastic recycle machine a form befitting processing. Finally the ultimate
section which is referred to as the metering zone stabilizes the effervescent stream of the matrix and
ensures the extruded merchandise includes a uniform thickness, shape, and size. A continual and
regular uniform screw flight depth and pitch helps to maintain constant high pressure making sure a
uniform delivery level of extrudates through the extrusion die and therefore a uniform extruded
item.
Amount 3: Screw geometry (extrusion) [9].

As well as the above-mentioned devices, downstream auxiliary machines for cooling, cutting, and
collecting the finished item can be typically employed. Mass stream feeders to meter substances in
to the feed hopper accurately, pelletizers, spheronizer, roller/calendaring device as a way to produce
continuous films, and process analytical technology such as for example near infrared (NIR) and
Raman, ultrasound, and DSC systems are also options. Through the entire whole process, the temp
in all zones is generally controlled by electrical heating system bands and monitored by
thermocouples.
The single-screw extrusion system is simple and offers lots of advantages but still does not acquire
the mixing capacity for a twin-screw equipment and for that reason is not the most well-liked
approach for the production of most pharmaceutical formulations. Moreover, a twin-screw extruder
offers much greater versatility (method manipulation and optimisation) in accommodating a wider
range of pharmaceutical formulations making this setup a lot more constructive. The rotation of the
screws in the extruder barrel may either get corotating (same path) or counter-rotating (opposite
direction), both directions being equivalent from a digesting perspective (Figure 4). A greater
degree of conveying and much shorter residence times happen to be achievable with an
intermeshing set up. Furthermore, the use of reverse-conveying and forward-conveying components,
kneading blocks, and different intricate styles as a way of improving or controlling the amount of
mixing required can help the configuration of the screws themselves to end up being varied [16].
Figure 4: A twin-screw extruder and screws [9].
4. Advantages and Disadvantages of HME
HME offers several advantages over conventionally available pharmaceutical processing techniques
including (a) increased solubility and bioavailability of drinking water insoluble substances; (b)
solvent-free nonambient process; (c) economical process with reduced production time, fewer
processing measures, and a continuous operation; (d) capabilities of sustained, altered, and targeted
launching; (e) better content material uniformity in extrudates; (f) no requirements for the
compressibility of active ingredients; (g) uniform dispersion of good particles; (h) good stableness at
changing pH and wetness levels and safe software in individuals; (i) reduced amount of unit
procedures and production of an array of performance dosage forms (j) a variety of screw
geometries [17-21].
However, HME has most disadvantages as well. The main drawbacks of HME incorporate thermal
process (drug/polymer stability), usage of a limited amount of polymers, high stream properties of
polymers, and excipients required rather than suitable for high heat sensitive molecules such as
microbial species and proteins comparatively