Advantages of HME for film formation include the following:
- No need to use solvent or water
- Fewer processing steps
- Compressibility properties of the API may not be of importance
- Good dispersion mechanism for poorly soluble drugs
- More uniform dispersion of the fine particles because of intense mixing and agitation
- Less energy compared with high-shear methods
- Minimum product waste
- Possibility of scale-up
- Good control of operating parameters.
In the HME process, the API and other excipients are mixed in a dry state, the heating process is started, and the molten
mass is extruded out of the hot-melt extruder. The advantage of this process is the complete elimination of the solvent. The
films are allowed to cool and are cut to the desired size. The high temperature used in the process makes it suitable for
thermostable drugs. Drugs that are sensitive to temperature cannot be used in this process.
Figure 1: Crucial factors involved in manufacturing orally disintegrating films using the solvent-casting method.
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Table I compares solvent-casting and HME for the manufacture of ODFs. Solvent casting is a hydrous process suitable for thermolabile
and thermostable drugs in comparison to HME, which is anhydrous and requires thermostable drugs. Repka et al. studied the influence of chlorpheniramine maleate (CPM) on topical HPC films by HME (5). CPM has been reported to function
as an effective plasticizer, thereby increasing percent elongation and decreasing tensile strength in a concentration-dependent
manner. CPM also acts as a processing aid in the extrusion of hot-melt films by allowing film processing at lower temperatures
(6).
An evaluation of HME and the in vivo bioadhesive properties of HPC films containing seven polymer additives on the epidermis of human subjects was performed (7).
HPC films containing additives with and without plasticizers were prepared by HME. Incorporation of a carbomer (Carbopol 971P
NF, Lubrizol, Cleveland, OH) and polycarbophil into HPC films increased bioadhesion significantly. Many studies were conducted
using HME for preparing solid dispersions. It was reported that melt extrusion of miscible components resulted in amorphous
solid-solution formation, whereas extrusion of an immiscible component led to the amorphous drug dispersed in a crystalline
excipient (8). The process has been useful in preparing solid dispersions in a single step. An extruder consists of two distinct
parts. The first part consists of a conveyer system that transports the material and imparts a degree of distributive mixing.
A second part, a dye system, forms the materials into the required shape. The drug-carrier mix is filled in the hopper and
is conveyed, mixed, and melted by the extruder. The die shapes the melt in the required form such as granules, pellets, films,
or powder, which can be further processed into conventional tablets or capsules. Oxygen and moisture should be completely
eliminated for substances susceptible to oxidation and hydrolysis (9).
Semisolid casting
. In the semisolid-casting method, a solution of the water-soluble, film-forming polymer is prepared. The resulting solution
is added to a solution of acid insoluble polymer (e.g., cellulose acetate phthalate and cellulose acetate butyrate), which
is previously prepared in ammonium or sodium hydroxide. The appropriate amount of plasticizer is added to obtain a gel mass.
The prepared gel mass is cast into films or ribbons using a controlled heat source. The thickness of the film is controlled
between 0.015–0.05 in. (9).
Solid-dispersion extrusion
. The term solid dispersion refers to the dispersion of one or more APIs in an inert carrier in a solid state in the presence of amorphous hydrophilic
polymers using methods such as HME. In solid-dispersion extrusion, immiscible components are extruded with drug, and solid
dispersions are prepared. The solid dispersions are shaped into films by means of dies. The drug is dissolved in a suitable
liquid solvent. This solution is incorporated into the melt of polyols such as polyethylene glycol, obtained below 70 °C,
without removing the liquid solvent. The selected solvent or dissolved drug may not be miscible with the melt of the polyethylene
glycol. The polymorphic form of the drug precipitated in the solid dispersion may be affected by the liquid solvent used (9,
10).
Rolling method
. In the rolling method, a solution or suspension containing the drug is rolled on a carrier. The solvent is mainly water
and a mixture of water and alcohol. The film is dried on the rollers and cut into desired size and shapes. The film is made
by preparing a premix and adding the API, and film is subsequently formed (11). The premix or master batch containing the
film-forming polymer, polar solvent, and other excipients, except the API, are added to the master-batch feed tank. A predetermined
amount of the master batch is controlled and fed through a metering pump and control valve to the mixers. The required amount
of the drug is added to the desired mixer through an opening. After blending the API with the master batch to provide a uniform
matrix, the matrix is fed to the pan using metering pumps. The thickness of the film is controlled using a metering roller.
The film is finally formed on the substrate and carried away via the support roller. The wet film is dried using controlled bottom drying, preferably in the absence of external air currents
or heat on the surface of the film.
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