Pharmaceutical Technology - Colloidal Dispersions PDF

# Pharmaceutical Technology - Colloidal Dispersions ## 3rd Stage 2021 ## Dr. SHAFAQ AL-AZZAWI ### Introduction - **Sol:** A general term to designate a dispersion of a solid substance in a liquid, solid, or gaseous medium. - **Hydro-** for water (hydrosol) - **Alco-** for alcohol (alcosol...

# Pharmaceutical Technology - Colloidal Dispersions ## 3rd Stage 2021 ## Dr. SHAFAQ AL-AZZAWI ### Introduction - **Sol:** A general term to designate a dispersion of a solid substance in a liquid, solid, or gaseous medium. - **Hydro-** for water (hydrosol) - **Alco-** for alcohol (alcosol) - **Aerosol:** A dispersion of a solid or a liquid in a gaseous phase. - **Colloidal Dispersion:** Particles fall between 1 nm and 0.5 µm, and colloidal particles are usually larger than atoms, ions, or molecules. ### Differences Between Colloidal Dispersions and True Solutions 1. **Particle Size:** Colloidal dispersions have larger particle sizes. 2. **Dispersing Media:** The nature of the dispersing media with respect to the disperse phase affects both: - **Ease of Preparation** - **Character of the dispersion** - **Lyophilic:** The disperse phase interacts appreciably with the dispersion medium, meaning solvent loving. - A single substance may be lyophobic with respect to one dispersion medium and lyophilic with respect to another. - **Lyophobic:** The degree of attraction is small, meaning solvent hating. ### Types of Colloidal Sols 1. **Lyophilic colloids**: Large organic molecules that disperse readily upon addition to the dispersion medium to form colloidal dispersions. - As more molecules of the substance are added to the sol, the viscosity increases, and when the concentration of molecules is sufficiently high, the liquid sol may become a semisolid or solid dispersion, termed a gel. - **Gels:** Owe their rigidity to a network of the disperse phase that entraps and holds the dispersion medium. - A change in temperature can cause certain gels to resume their sol or liquid state. - Some gels become fluid on agitation, only resume their solid or semisolid state after remaining undisturbed for a period of time, this phenomenon is known as thixotropy. 2. **Lyophobic colloids:** Generally composed of inorganic particles. - There is little if any interaction between the two phases. - Unlike lyophilic colloids, lyophobic materials do not spontaneously disperse but must be encouraged to do so by special individualized procedures. 3. **Amphiphilic colloids:** Form dispersions in both aqueous and nonaqueous media. ### Classification and Types of Gels - **Inorganic and Organic Gels:** - Majority of inorganic hydrogels are two-phase systems, such as aluminum hydroxide gel and bentonite magma. - Majority of organic gels are single-phase systems, as carbomer and tragacanth. - **Hydrogels and Organogels:** - **Hydrogels:** Include organic hydrogels, natural and synthetic gums, and inorganic hydrogels. - Examples include hydrophilic colloids such as silica, bentonite, tragacanth, sodium alginate, methylcellulose, sodium carboxymethylcellulose. - **Organogels:** Include the hydrocarbons, animal and vegetable fats, soap base greases. ### Preparation of Magmas and Gels - **Inorganic:** Some magmas and gels are prepared by freshly precipitating the disperse phase. - Others are prepared by directly hydrating the inorganic chemical, which produces the disperse phase of the dispersion. - Thickening agents including propylene glycol, and hydroxypropyl cellulose may be used. - **Stability:** Due to the high degree of attraction between the disperse phase and the aqueous medium in both magmas and gels, they remain uniform on standing with little settling of the disperse phase. - A supernatant layer of the dispersion medium develops, but the uniformity of the preparation is easily reestablished by moderate shaking. - Should be shaken before use. ### Gelling Agents - Thicken and stabilize liquid solutions. - Dissolve in the liquid as colloid mixture that forms an internal structure giving the resulting gel an appearance of a solid matter. ### Examples of Gelling Agents - **Alginic acid:** - Swells in water to about 200 to 300 times its own weight without dissolving. - **Carbomer (Carbopol) resins:** - High-MW acid-based polymers. - **Colloidal silicon dioxide:** - Adsorbs large quantities of water without liquefying. - **Gelatin:** - Dispersed in hot water and cooled to form gels. - **Magnesium aluminum silicate (Veegum):** - In concentrations of about 10% forms a thixotropic gel. - **Methylcellulose:** - A long-chain substituted cellulose, forms gel at 5% concentration. - **Other:** - Bentonite, Acacia, Xanthan gum, Tragacanth gum, Povidone, Carboxymethylcellulose, Carboxymethylcellulose (CMC) Sodium th ### Gel Formulation Considerations 1. **Dissolution:** The powdered polymers, when added to water, may form temporary gels with slow dissolution. 2. **Kinetic Energy:** As a hot colloidal dispersion of gelatin cools, the gelatin macromolecules lose kinetic energy. With reduced kinetic energy, or thermal agitation, the gelatin macromolecules are associated through dipole-dipole interaction into elongated aggregates. 3. **Polymer Solutions:** Polymer solutions tend to cast gels because the solute consists of long, flexible chains that tend to become entangled, attract each other by secondary forces, and even crystallize. 4. **Inorganic Salts:** Inorganic salts will compete with the water in a gel and cause gelation at lower concentrations. This is usually reversible; upon addition of water, the gels will reform. 5. **Storage:** Aqueous polymer solutions, especially of cellulose derivatives, are stored for about 48 hours after dissolution to promote full hydration and maximum viscosity and clarity. ### Examples of Magmas and Gels - **Bentonite Magma, NF:** Used as a suspending agent. - **Sodium Fluoride and Phosphoric Acid Gel, USP:** Applied topically to the teeth as a dental care prophylactic. - **Fluocinonide Gel, USP:** An antiinflammatory corticosteroid. - **Tretinoin Gel, USP:** An irritant that stimulates epidermal cell turnover, causes peeling, and is effective in the treatment of acne. - **Other examples:** Erythromycin and benzoyl peroxide topical gel and clindamycin topical gel. ### Antacids - **Aluminum Phosphate Gel USP:** - **Aluminum Hydroxide Gel, USP:** ### Bentonite Magma, NF - A preparation of 5% bentonite, a colloidal hydrated aluminum silicate, in purified water. - Prepared mechanically in a blender with the bentonite added directly to the purified water while the machine is running. - Bentonite, which is insoluble in water, swells to approximately 12 times its volume upon addition to water. - **Suspending Agent:** Its pH must be considered, as it can affect the suspending capacity of the magma, which is drastically reduced if the pH is lowered to about pH 7. ### Aluminum Hydroxide Gel, USP - An aqueous product of a gelatinous precipitate composed of insoluble aluminum hydroxide and the hydrated aluminum oxide, equivalent to about 4% aluminum oxide. - Prepared by chemical reaction, using various reactants. - The USP permits the addition of peppermint oil, glycerin, sorbitol, sucrose, saccharin, or other flavorants and sweeteners as well as suitable antimicrobial agents. - **A white and viscous antacid preparation:** - Neutralizes a portion of the gastric hydrochloric acid, and by virtue of its gelatinous, viscous, and insoluble character, coats the inflamed and perhaps ulcerated gastric surface. - Useful in the treatment of hyperacidity and peptic ulcers. - **Disadvantage:** Constipating effects. - **Bioavailability:** Because it possesses a trivalent cation, aluminum hydroxide interferes with the bioavailability of tetracycline by chelating with the antibiotic in the gastrointestinal tract. - **Bioavailability:** Aluminum hydroxide gel has also been implicated in decreasing the bioavailability of other drugs by adsorption onto the gel. - May be necessary to increase the dose of the second drug if aluminum hydroxide gel administration remains the same. ### Milk of Magnesia - A preparation containing 7 to 8.5% magnesium hydroxide. - **Prepared:** By a reaction between sodium hydroxide and magnesium sulfate. - **Acid-Neutralizing:** A dose of 5 mL is usually necessary. - A higher dose (15 mL) may cause diarrhea. - **Antacid:** Combined with aluminum hydroxide to make a more palatable product with optimum buffering of stomach contents at a pH of 4 to 5 and less of a chance for diarrhea or constipation to occur. ### Starch Glycerite - Composed of Starch, benzoic acid, purified water and glycerin. - Used as a topical vehicle and protectant. ### Proper Administration and Use of Disperse Systems - **Oral Disperse Systems:** Measured by spoonful or a dropper, or calibrating devices depending on the appropriate dose. - **Reconstituted Products:** A pharmacist needs to provide thorough instructions for reconstitution, stability, and use since many reconstituted products are suspensions. - **Oral Antibiotic Suspensions:** May be misadministered directly into the ear by some patients. - **Stability:** Stability problems with the drug usually dictate that it be stored in the refrigerator until it is consumed. - **Absorption:** Pharmacists should be aware of certain preparations that interfere with absorption of other drugs (e.g., aluminum hydroxide gel, cholestyramine, and kaolin).