Pharmaceutical Manufacturing Handbook: Production and

302 SEMISOLID DOSAGES: OINTMENTS, CREAMS, AND GELS
dispersing agents. Care should be taken to avoid the evaporation or degradation of
these cosolvents and dispersing agents during the preparation of gels.
Processing Conditions and Duration of Swelling The processing temperature, pH
of the dispersion, and duration of swelling are critical parameters in the preparation
of gels. These conditions vary with each gelling agent. For instance, hot water is
preferred for gelatin and polyvinyl alcohol, and cold water is preferred for methylcellulose
dispersions. Carbomers, guar gum, hydroxypropyl cellulose, poloxamer,
and tragacanth form gels at weakly acidic or near - neutral pH conditions (pH 5 – 8).
Gelling agents such as carboxymethyl cellulose sodium, hydroxypropylmethyl cellulose,
and sodium alginate form gels over a wide pH range (4 – 10). Hydroxyethyl
cellulose forms gel at alkaline pH condition. A swelling duration of about 24 – 48 h
generally helps in obtaining homogeneous gels. Natural gums need about 24 h and
cellulose polymers require about 48 h for complete hydration.
Removal of Entrapped Air Entrapment of air bubbles in the gel matrix is a
common issue, especially when the swelling process involves a mixing procedure or
the drug and other additives are added after the swelling process. Positioning the
propeller at the bottom of the mixing container minimizes this issue to a larger
extent. Further removal of air bubbles can be achieved by long - term standing, low -
temperature storage, sonication, or inclusion of silicon antifoaming agents. In large -
scale production, vacuum vessel deaerators are used to remove the entrapped air.
Packaging Being viscous and non - Newtonian systems, gels need high attention
during packing into containers. Usually they are packed into squeeze tubes or jars
made of plastic materials. Aluminum containers are also used when the product pH
is slightly acidic. Pump dispensers and prefi lled syringes are sometimes used for
packing gels. As most of the gels contain an aqueous phase, preservation in airtight
containers helps in protecting them from microbial attack. Usually they are preserved
at room temperature and protected from direct sunlight and moisture.
In large - scale production, different mills, separators, mixers, deaerators, shifters,
and packaging machines are used. Most of this equipment is similar to those discussed
under ointments and creams. Figure 3 shows a “ one - bowl ” vacuum processing
machine manufactured by FrymaKoruma - Rheinfelden (Romaco) for the
preparation gels. Batch sizes ranging from 15 to 160 L are processed using this
machine. It uses an extremely effi cient high - shear rotor/stator system for homogenizing
and a counterrotating mixing system for macromixing. The raw materials are
drawn into the multichamber system of the homogenizer by vacuum and then mixed
and pumped into the homogenizing zone. The product which enters the vessel is
mixed, sheared, and recirculated. All the entrapped air is removed during the recirculation.
The machine also has an insulated jacket for controlling the processing
temperature.
4.2.3.7
Evaluation
Various pharmacopeial and nonpharmacopeial tests are carried out to evaluate the
physicochemical, microbial, in vitro, and in vivo characteristics of gels. These tests
are meant for assessing the quality of gel formulations and minimizing the batch -