Pharmaceutical Formulations Quiz

Liquid Dosage Forms - Post Lab Notes

• Liniments: Derived from Latin "linere" (to anoint), liniments are alcoholic or oleaginous solutions/emulsions of medicinal substances for rubbing on the skin. They are applied with friction/rubbing (embrocation)
• Liniments are typically used for external application and are easier to apply than ointments but denser than water and liquid at room temperature.
• Liniments come in the form of solutions, emulsions, or suspensions.
• Types of Liniments:
  • Alcoholic liniments are used for counterirritant, rubefacient, or penetrating action. Penetrate the skin readily.
  • Oleaginous (oily) liniments are milder, better for massage, and less irritating. Do not penetrate the skin as deeply as alcoholic liniments.
• Things to consider when using liniments:
  • Avoid broken or bruised skin.
  • External use only; do not ingest.
  • Many formulations are emulsions; shake well before use for even distribution.
  • Label liniments as instructions say.

Camphorated Soap Liniment

• Synonyms: Linimentum Camphoras El Salponis, Linimentum Saponis molis, Linimentum Saponis Camphoratum, Soap Liniment, Liquid Opodeldoc
• Uses: Rubefacient, treating sore/inflamed joints, muscles, tendons, and ligaments; local anesthetic for sprains/strains/bruises; alleviation of arthritis, bursitis and rheumatism; circulation problems
• Category: Alcohol-based liniment
• Method: Agitation (with or without heat)

Non-Aqueous Liquid Dosage Forms

• Glycerites: Glycerite solutions/mixtures of medicinal substances, mostly viscous (some jelly-like). Used to create aqueous/alcoholic dilutions of readily soluble substances. Also used as protectants, emollients, and pill excipients.
• Glycerite must be stored in tightly closed containers owing to their hygroscopic nature
• Glycerin: (glycerol): colorless, odorless, viscous liquid. Sweet tasting and nontoxic
• Not suitable for substances that react to strong oxidizers, as it is a reducing agent. Can react with strong oxidizers like KMnO4, chromium trioxide, and KClO3 resulting in explosion.
• Converts into nitroglycerin when exposed to strong HNO3 or H2SO4.
• Soluble in water; hygroscopic

Starch Glycerite

• Synonyms: Glyceratum amyli. Starch Glycerin
• Uses: Topical vehicle & protectant
• Label: Red
• Container: 30 mL Wide Mouth Amber Bottle
• REMARKS: The heat ruptures the starch grains allowing water to hydrate the linear and beta subunits and branched starch molecules which trap the dispersion medium in the interstices, forming a gel-like consistency. Trituration is used in preparation. Should be stored in a tightly sealed container.

Emulsions

• Emulsions are two-phase systems in which one liquid is dispersed throughout another immiscible liquid in the form of small globules.
• Components:
  • Dispersed liquid (internal phase)
  • Dispersion medium (external phase)
  • Emulsifying agent (intermediate agent)
• Types of Emulsifying Agents:
  • Natural - gelatin, egg yolk, casein, wool fat, cholesterol, acacia, tragacanth, chondrus, pectin, caraya, carrageenan
  • Synthetic- Mg(OH)2, Al(OH)3, magnesium trisilicate, Kaolin, Bentonite Magma, benzalkonium chloride, cetylpyridinium chloride, SLS, PEG 400, spans, tweens, lecithin

Method of Preparation

• Wet or English: Gum and water first, then add oil in one direction, creamy, sticky mixture (crackling sound).
• Dry or Continental: Gum and oil first, then add water in one direction. Creamy, sticky mixture (crackling sound).
• Bottle or Forbes: Oil/water/gum mixture, shake vigorously
• Auxiliary methods: Hand homogenizer, In-situ soap (calcium or soft soap)
• Microemulsions: 100-1000 Angstroms particle size

Problems in Emulsions

• Creaming: upward movement of dispersed droplets relative to continuous phase.
• Aggregation/flocculation is the collection of dispersed droplets which causes creaming.
• Coalescence happens when droplets merge.
• Cracking: complete separation of the two phases (o/w or w/o).
• Phase inversion if the medium changes from oil/water (o/w) to water/oil (w/o) often due to evaporation.

Identifying Emulsions

• Drop dilution test-add water.
• Dye solubility- Oil soluble (sudan red), Water soluble (amaranth green).
• Electronic Conductivity Test
• Fluorescence Test

HLB System

• Selecting emulsifying agents based on their hydrophilic and lipophilic balance.
• HLB values usually between 1 and 20. HLB values between 8 and 18 are hydrophilic (o/w); values of 3 to 6 produce lipophilic (w/o)
• Table 14.3 Activity and HLB Value of Surfactants: Shows different surfactant groups and their typical HLB values (antifoam, emulsifiers(oil/water), wetting agent, emulsifiers(water/oil), solubilizers, detergents.)

Mineral Oil Emulsion

• Synonyms: Liquid Petrolatum Emulsion
• Uses: Lubricating cathartic (30mL dose)
• Label: White, auxiliary (shake well)
• Container: 30ml Wide Mouth Amber Bottle
• Method: Dry Gum Method
• REMARKS: Mineral Oil as cathartic, Acacia as emulsifying agent, syrup as sweetener, vanillin as flavoring, alcohol as preservative. Keep in cool dry place below 25°C, “Shake well” instruction.

Mixtures (in Liquid Dosage Forms)

• Mixtures are aqueous liquid preparations containing undissolved, insoluble solids (suspensoids).
• Good mixtures have small, finely divided particles (insoluble substances). Should be uniformly dispersed throughout the preparation.
• Suspension must be accomplished by use of colloids and special methods of precipitation.

Classification of Dispersed Systems

• Class: Molecular Dispersion, Colloidal Dispersion, Course Dispersion
• Range of particle size: Less than 1nm, 1nm to 0.5 μm, greater than 0.5 μm
• Characteristics: Characteristics of system (diffusion, invisible in miscroscope,(ordinary loss), diffuse slowly/visible in EM/UL, etc.)

Chalk Mixture

• Synonyms: Mixture de Creta, Mistura Cratae, Dropped Chalk, Calcium carbonate chalk, Precipitated Calcium Carbonate
• Uses: Antacid, antidiarrheal agent
• Label: White, auxiliary (shake well)
• Container: 30 ml Flint bottle
• Method: Simple Hydration
• REMARKS: Glycerin (as a viscosity agent) is added to retard particle settling and chalk mixtures should be shaken for proper dosage

Gels (in Liquid Dosage Forms)

• Semisolid systems - either small inorganic particles or large organic molecules dispersed in a liquid.
• Also classified as semi-rigid 3D networks of particles or solvated macromolecules of the dispersed phase.
• Very fine particle size leading to broad surface area, resulting in maximum adsorption capacity.
• Contain various ingredients: peppermint oil, glycerin, sorbitol, sucrose, saccharin, and flavor/preservative. Not exceeding 0.5%.
• Two-phase systems: Thixotropic suspensions, Single-phase systems of synthetic macromolecules.

General Classification of Gels

• Inorganic: Aluminum hydroxide gel, Bentonite magma
• Organic: Carbopol, Tragacanth
• Hydrogels: Organic(pectin paste, tragacanth jelly), Natural and synthetic gums (methylcellulose, sodium CMC, Pluronic) Inorganic (Bentonite gel, Veegum, silica)
• Organogels: Petrolatum, mineral oil/polyethylene gel (Plastibase), animal/vegetable fats (lard, cocoa butter), soap base, greases (aluminum stearate with heavy mineral oil gel), hydrophilic organogels (carbowax bases, PEG ointment), Polar, Nonionic

Preparation of Gels

• Gelling agents (ex: acacia, alginic acid, bentonite, CMC sodium etc..) are used to make a suspension of the insoluble ingredients, resulting in a gel.

Aluminum Hydroxide Gel

• Synonyms: Colloidal Aluminum Hydroxide, Amphojel, Alternagel
• Uses: Antacid (not for alkalosis), heartburn, hyperacidity, peptic ulcers, gastritis, esophagitis, skin protectant (mild astringent)
• Category: Medicated Gel
• Label: White label, Shake well
• Container: 30 ml wide mouth amber bottle
• Method: Chemical Reaction
• Remarks: (Additional details regarding side effects, additives, usage and mixing)

Lotion

• Aqueous or alcoholic preparation containing insoluble materials (suspension, emulsions).
• Applied without friction.
• Preferred over semi-solid preparations due to non-greasy and broad spreadability.. Often used as washes
• Label: For external use only. Shake well before use.

Method Preparation of Lotions

• Trituration: Ingredients are triturated to form a smooth paste. The liquid phase is carefully added to the paste.
• Chemical interaction: Ingredients interact in a chemical reaction with resulting solid/liquid mixture.
• Preparation of Clear Solutions: Where the active ingredient is water-soluble.

Calamine Topical Lotion

• Ingredients: Ferric oxide, calamine, zinc oxide, glycerin, bentonite, calcium hydroxide.
• Uses: Antipruritic, astringent, antiseptic, topical protectant, treating skin conditions (itching, infection, allergy, pain)
• Category: Lotion
• Label: Red label
• Container: 30 ml amber bottle
• Method: Levigation and Trituration
• Remarks: Most lotions are oil-in-water emulsions. Water-in-oil lotions are also developed.

Suspension

• Liquid preparation containing non-soluble solids.
• Solids (suspensoids) are dispersed uniformly throughout the liquid (vehicle/medium)
• Must be held in suspension (use appropriate suspending/thickening agents)
• Dispersing agents prevent clumping so that the liquid and solid phases can remain separated. Needs to be shaken.

Characteristics of a Good Suspension

• Should easily re-suspend; taking a moderate time to settle.
• Easy to pour, not watery, and not gritty in texture.
• Have a pleasant odor, color, and taste.
• Physically, chemically, microbiologically stable (no adverse chemical reaction/color changes within a reasonable time frame).

Other Medical Devices

• Comprehensive list of various medical devices (blood sampling kits, blood transfusion sets, breathing circuits, cannulas, catheters).
• Includes additional medical devices such as cervical collars, clinical thermometers, abdominal pads, access/injection ports.
• Additional medical devices (aphoresis kits, anesthesia sets, bandages, blood bags, clip appliers/clips, skin staplers, catheter condoms, contact lens solutions, etc.)
• Additional medical devices, including devices like cotton, operating lamps & tables, otoscopes, dental fillers, scalpel, dialyzers, ultrasound scanners, bone drills, earwax removers etc.