PHARMAEUTICAL TECHNOLOGY II:

SEMISOLIDS FORMULATIONS (GELS)

Balqees Saeed
FACULTY OF PHARMACY, AL WADI INTERNATIONAL UNIVERSITY
2019-2020
 Semisolids formulations (gels)

Table of Contents
1 Semi-solid formulations ............................................................................................................................ 1
1.3 Gels..................................................................................................................................................... 1
1.3.1 Classification of jellies according to use .................................................................................. 1
1.3.2 Classification of jellies according to the nature of the 3-D network of particles .................. 2
1.3.3 Excipients used in gel formation .............................................................................................. 3
1.3.4 Manufacture of pharmaceutical gels ....................................................................................... 3
1.3.5 Evaluation of semisolid dosage forms ..................................................................................... 4
1.3.6 Filling semisolid ......................................................................................................................... 4
1.3.7 Packaging semisolid Preparations ............................................................................................ 5
2 Liquid formulations for external application ............................................................................................ 5
3 Solid formulations...................................................................................................................................... 5

Topical preparations

1 Semi-solid formulations
1.3 Gels
• They are semisolid systems in which a liquid phase is embedded within a three-
dimensional polymeric matrix having a high degree of physical or chemical cross-linking
with the following characters:
1. Excellent spreading and cooling effect due to solvent evaporation.
2. The vehicle may be aqueous, alcoholic (non-aqueous), hydroalcoholic.
3. The colloidal particles may be dispersed solids, e.g. kaolin, bentonite or dispersed polymers.
4. The API that tends to hydrolysis should not be formulated into aqueous gels.
5. Gels may thicken on standing, and must be shaken before use to liquefy the gel and enable
pouring.
6. Jellies are either as transparent as water which are an aesthetically pleasing or are turbid
or translucent, and non-greasy semisolid gels.

1.3.1 Classification of jellies according to use

1. Medicated jellies

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 Semisolids formulations (gels)

o Administered to the skin, the eye, the nose, the vagina, and the rectum.
o Used as wound dressings, and for the controlled delivery of API at the site of implantation.
2. Lubricant jellies
o Used for, catheters, and electrodiagnostic equipment.
o Must be sterile for articles inserted into sterile regions of the body.
3. Miscellaneous jellies
o Patch testing: to detect allergens sensitivity.
o Electrocardiography: to reduce electrical resistance between patients’ skin and electrodes
of the cardiograph (contains Nacl to provide good conductivity).
1.3.2 Classification of jellies according to the nature of the 3-D network of particles
1. Gels based on dispersed solids
• It is a gel mass consisting of floccules of small particles, bonding together by a weak van
der Waals bond that are broken by shaken e.g. Aluminium Hydroxide Gel USP.
• On standing, the particles are collided, flocculation occurs and the gel is reformed.
2. Gels based on hydrophilic polymers
• It is a gel that is manufactured by dispersing hydrophilic polymers within an appropriate
aqueous vehicle. There are two types:
I. Type 1 gels (hydrogels)
• The interaction between the polymer chains is a strong covalent and is held together by
molecules that cross-link the adjacent chains (termed cross-linkers) e.g. (ethyleneglycol
dimethacrylate EGDMA).
• Can absorb a large mass of aqueous fluid, swells, cannot dissolve, have excellent flexibility.
• Do not flow when exposed to stress.
II. Type 2 gels
• The interactions between the polymer chains are weaker bonds e.g. hydrogen bonding
or van der Waals interactions.

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 Semisolids formulations (gels)

• The application of stresses (e.g. heat) →temporary (reversible) destruction of these

bonds →liquefy the gel.
• The majority of gels are type 2 gels.

1.3.3 Excipients used in gel formation

1. Gelling agents
a. Cellulose derivatives: methylcellulose (MC), hydroxyethyl cellulose (HEC), hydroxypropyl
cellulose (HPC), and sodium carboxymethylcellulose (Na-CMC) .
b. Natural polymers: Carrageenan from red seaweed, Alginic acid or Na alginate from algae,
Tragacanth, Pectin, Gelatin and, Starch.
c. Carbopol.

2. Purified water is the normal solvent.

3. Buffers.
4. Co-solvents: to enhance the solubility of API and to enhance drug permeation across the
skin e.g. alcohol, propylene glycol, glycerol, PEG 400.
5. Preservatives, such as methylparaben and propylparaben.
6. Antioxidants: water-soluble antioxidants, e.g. sodium formaldehyde.
7. Chelating agents e.g. ethylene diamine tetra acetic acid EDTA.

1.3.4 Manufacture of pharmaceutical gels

1. Water soluble excipients are dissolved in the vehicle in a mixing vessel with mechanical
stirring (Figure 1).
2. The hydrophilic polymer must be added to the stirred mixture slowly to prevent
aggregation and stirring is continued until dissolution of the polymer is occurred.
3. Gels may be formed by dispersing the molecule in the continuous phase (e.g., by heating
starch), or by cross-linking the dispersed molecules by changing the pH (as for carbomers).
4. Excessive stirring results in entrapment of air.

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 Semisolids formulations (gels)

1.3.5 Evaluation of semisolid dosage forms

1. Uniformity of drug content (between 95–105%).
2. pH measurement (5 - 6.5).
3. Drug release rate using an in vitro test.
4. Viscosity measurements using viscometer.
5. Microbial test: Figure 1 Magnetic Stirrer and Mechanical Stirrer

o Must meet acceptable standards for microbial content.

o Dermatological product should be tested for Staphylococcus aureus and Pseudomonas
aeruginosa.
o Rectal or urethral or vaginal product should be tested for yeast and molds.

7. Sterility test: for sterile semi-solid formulations to be applied to the skin (for wound or
burn indications) and for ophthalmic ointment.
8. Stability studies:
o Performed at 25°C/60% relative humidity (RH), 30°/65% RH, and 40°C/75% RH for t = 0, 1,
3, 6, 9, 12, 18, and 24 months.
o In case of emulsions and creams:
a. Physical stability or appearance (e.g. nonseparation of emulsion phases, and homogeneity
of color).
b. Droplet size analysis using optical microscopy, image analysis, and laser light scattering
techniques (coalescence→↑ droplet sizes).
c. Droplet charge using zeta potential.
d. Rheological measurements using rheometers.

1.3.6 Filling semisolid

a. In a small scale:
• Transferring the weighed amount into the jar with a spatula.
• Ointments prepared by fusion may be poured directly into the jar or tube to congeal in it.
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 Semisolids formulations (gels)

• Tubes are filled from the open back end of the tube, then they are closed and sealed.
b. In large-scale: filling, closing, crimping, and labeling are carried
out automatically.

1.3.7 Packaging semisolid Preparations

• Topical products are packaged in either jars, tubes, or syringes.
• Ophthalmic, vaginal, and rectal semisolid products are packaged
in tubes or syringes.
• Light- sensitive preparations are packaged in opaque or light-
resistant containers.
• Tubes of aluminum generally are coated with an epoxy resin, to Figure 2 Filling of semisolids
eliminate any interactions between the contents and the tube.
• Stored in well-closed containers to protect them against contamination e.g. glass, or
plastic, or aluminum and in a cool place to prevent separation of the product in heat.

2 Liquid formulations for external application

1. Simple single-phase solutions (e.g. chlorhexidine solutions for skin disinfection).
2. Emulsions and suspensions.
3. Lotions e.g. calamine lotion
o They are liquid-based formulations (solutions or suspensions or emulsions), may contain
co-solvent and coolant (e.g. alcohol), Humectants, vehicle (e.g. purified water), and
preservatives.

3 Solid formulations
1. Powders.
2. Dusting powders to reduce friction between skin surfaces.
3. Topical sprays available to deposit powders on the skin surface (consist of volatile solvent
and API).