Solutiones pharmaceuticae: genera et utilitates

• Solutions
  • Liquid preparations containing one or more soluble chemical substances dissolved in a specified solvent
  • Solute + Solvent

Advantages of Solutions

• Completely homogenous doses
• Immediate availability for absorption
• Good for patients with difficulty swallowing solid dosage forms

Disadvantages of Solutions

• Drug Stability
• Bulky
• Dosing inaccuracy
• Taste masking can be difficult

Pharmaceutical solutions

• Aqueous solutions
  • Syrup
  • Elixir
  • Aromatic water
  • Douche
  • Enema
  • Gargle
  • Mouthwash
  • Nasal solution
  • Otic solution
  • Irrigation
• Nonaqueous solutions
  • Liniment
  • Collodion
  • Extract
  • Tincture
  • Fluidextract

Syrup

• Aqueous solution containing sugar
• Usually sucrose; concentration is 60-80%

Elixir

• Clear, sweetened hydroalcoholic liquid intended for oral use
• Usually less sweet than syrups and less viscous
• Alcohol range: 5-40%

Aromatic water

• Clear, aqueous solutions saturated with volatile oils or other aromatic substances
• Used to provide a pleasant flavor or odor

Douche

• Aqueous solution directed against a part or into a cavity of the body
• Cleansing agent
• Antiseptic agent

Enema

• Rectal injection used to evacuate the bowel (evacuation enemas)
• Influence the general system by absorption (retention enemas)

Gargle

• Aqueous solution used to treat the pharynx and nasopharynx
• Forced into the back of the throat and agitated by expulsion of air from the lungs

Mouthwash

• Aqueous solution used to cleanse and treat the oral cavity

Nasal solution

• Aqueous solution designed to be instilled into the nostrils

Otic solution

• Solution instilled into the ear

Irrigation

• Aqueous solution used to wash or bathe a body cavity or wound
• Large volume

Liniment

• Alcoholic or oleaginous solutions or emulsions intended for external application to the skin
• Applied with rubbing

Collodion

• Liquid preparation containing pyroxylin in a mixture of ethyl ether and alcohol

Extract

• Concentrated preparation of vegetable or animal drug obtained by removal of the active constituents with suitable solvents
• Evaporation of all or nearly all of the solvent
• Adjustment of the residual mass or powder to the prescribed standard

Tincture

• Alcoholic or hydroalcoholic solution prepared from vegetable materials or from chemical substances

Fluidextract

• Liquid preparation of vegetable drugs
• Each milliliter contains the therapeutic activity of 1 gram of the drug

Solubility

• Extent to which a solute dissolves in a solvent

Miscibility

• Capability of two or more liquids to form a homogenous mixture

Factors affecting solubility

• Temperature
  • Most substances increase solubility with temperature
  • Endothermic: absorbs heat
  • Exothermic: releases heat
• Solute
  • Molecular size
  • Crystal form
• Solvent
  • Polarity
  • Solubility parameter
• Other factors
  • pH
  • Salt form

Solubility Expression

• Very soluble: Less than 1 part of solvent needed for 1 part of solute
• Freely soluble: 1-10 parts of solvent needed for 1 part of solute
• Soluble: 10-30 parts of solvent needed for 1 part of solute
• Sparingly soluble: 30-100 parts of solvent needed for 1 part of solute
• Slightly soluble: 100-1,000 parts of solvent needed for 1 part of solute
• Very slightly soluble: 1,000-10,000 parts of solvent needed for 1 part of solute
• Practically insoluble: More than 10,000 parts of solvent needed for 1 part of solute

Methods to increase drug solubility

• Solubilizing agent
• Cosolvent
• Chemical modification of the drug (salt formation)
• Reduce particle size
• Complexation

Solubilizing agent

• Added to a solution to increase the solubility of another substance
• Ex: surfactants, cyclodextrins

Cosolvent

• Water-miscible organic solvent used to increase the solubility of poorly water-soluble drugs
• Ex: ethanol, propylene glycol, glycerin

Salt formation

• Converting a drug into its salt form can significantly enhance its aqueous solubility
• Weak acids + base = soluble salt
• Weak bases + acid = soluble salt

Complexation

• Interaction of two or more molecules to form a complex
• Enhances solubility and stability

Preparation of Solutions (with heat)

• Heating a solvent can increase the rate at which a solute dissolves

Preparation of Solutions (without heat)

• Agitation of the solution can increase the rate at which a solute dissolves without need for heat

Rate of Solution

• Affected by:
  • Particle size of the solute
  • Extent of agitation
• Viscosity of the solvent
  • Temperature

Preservation of Solutions

• Simple syrup (85% sucrose)
• Antimicrobial preservatives
  • Benzoic acid
  • Sorbic acid
  • Methylparaben
  • Propylparaben

Clarity

• Maintained to ensure elegance and acceptability

Color

• Enhance acceptability
• Correlate with flavor

Viscosity

• Increased for patient palatability

Sweeteners

• Enhance acceptability
• Sucrose, dextrose, sorbitol, glycerol, artificial sweeteners

Flavorants

• Enhance acceptability
• Natural or synthetic

Compounding

• Practice of preparing personalized medications by combining ingredients

Good Compounding Practices (GCP) key elements

• Personnel
• Facilities
• Equipment
• Documentation
• Quality control
• Stability
• Packaging/Storage

Compounding Personnel

• Trained and qualified

Compounding Facilities

• Clean and suitable space

Compounding Equipment

• Calibrated and maintained

Compounding Documentation

• Complete and accurate records.

Quality control

• Procedures to ensure the compounded preparation meets specifications.

Compounding Stability

• Determine appropriate BUD (beyond use date)

BUDs

• Nonaqueous liquids and solids: 6 months or earliest expiration date of any ingredient, whichever is sooner
• Water-containing oral formulations: 14 days when stored at controlled cold temperatures
• Water-containing topical/dermal and mucosal liquid and semisolid formulations: 30 days

Packaging and Storage

• Proper containers and storage conditions

Suspension

• Liquid preparations containing finely divided drug particles distributed somewhat uniformly throughout a vehicle
• Insoluble drug dispersed in a liquid vehicle
• "Shake well" label

Advantages of Suspensions

• Good for drugs with low solubility
• Chemical stability
• Ease of administration
• Taste masking

Disadvantages of Suspensions

• Physical instability
• Sedimentation + compaction
• Difficult to re-suspend
• Bulky
• Dosing inaccuracy

Desired properties of suspensions

• Fine dispersion
• Slow settling
• Easy re-dispersibility
• Pourable
• Elegant

Wetting agents

• Reduce the interfacial tension between a solid and a liquid
• Help to displace air from the surface of the solid particles

Flocculating agents

• Electrolytes, surfactants, polymers
• Promote the formation of floccules

Viscosity enhancers

• Suspending agents
• Increase the viscosity of the suspension
• Help to keep the particles suspended

Types of Suspensions

• Flocculated suspensions
• Deflocculated suspensions

Flocculated suspensions

• Particles form loose aggregates (floccules)
• Settle rapidly
• Easy to re-suspend

Deflocculated suspensions

• Particles remain as discrete, unaggregated units
• Settle slowly
• Difficult to re-suspend

Formulation of Suspensions

• Wetting
• Dispersion
• Suspending

Formulation of Suspensions (Wetting)

• Reduce the interfacial tension with wetting agents
• Alcohol, glycerin, or other hygroscopic agents

Formulation of Suspensions (Dispersion)

• Dispersion of the drug particles in the vehicle using a high-shear mixer or a mortar and pestle

Formulation of Suspensions (Suspending)

• Addition of suspending agents (viscosity enhancers) to keep the particles suspended

Suspending agents

• Cellulose derivatives
• Natural gums
• Clays

Emulsion

• Two-phase system in which one liquid is dispersed throughout another liquid in the form of small droplets
• Immiscible liquids
• Internal (dispersed) phase
• External (continuous) phase

Advantages of Emulsions

• Enables administration of water-insoluble drugs
• Increases drug bioavailability
• Taste masking
• Can be used for topical, oral, or parenteral administration

Disadvantages of Emulsions

• Physical instability
• Emulsion breaking
• Requires preservatives
• Bulky

Types of Emulsions

• Oil-in-water (o/w)
  • Oil is the dispersed phase
  • Water is the continuous phase
• Water-in-oil (w/o)
  • Water is the dispersed phase
  • Oil is the continuous phase

Emulsifying agent

• Stabilizes an emulsion by preventing the dispersed phase from coalescing

HLB System

• Hydrophile-Lipophile Balance
• Classifies surfactants based on their relative affinity for water or oil

Generally, an HLB value between 8-18

• Indicates a surfactant is best suited for forming o/w emulsions

Generally, an HLB value between 4-8

• Indicates a surfactant is best suited for forming w/o emulsions

Preparation of Emulsions

• Continental (dry gum) method
• English (wet gum) method
• Bottle method

Continental (dry gum) method

• 4:2:1 ratio
• 4 parts oil, 2 parts water, 1 part emulsifier

English (wet gum) method

• 4:2:1 ratio
• 4 parts oil, 2 parts water, 1 part emulsifier

Bottle Method

• For volatile oils or oils of low viscosity

Emulsion Instability

• Creaming
• Coalescence
• Breaking
• Phase inversion

Creaming

• Upward movement of dispersed droplets (o/w) or downward movement (w/o)
• Reversible with shaking

Coalescence

• Merging of small droplets into larger droplets
• No sharp boundary between phases

Breaking

• Irreversible separation of the internal phase from the external phase

Phase inversion

• Emulsion changes from o/w to w/o or vice versa
• Can be caused by temperature changes or addition of electrolytes

Soluciones sunt praeparationes liquidae quae substantias chemicas solutas in solvente specifico continent. Habent commoda sicut doses homogeneas et promptam resorptionem, sed incommoda sicut stabilitatem medicamenti et magnitudinem habent. Varii typi solutionum includunt syrupos, elixires, et aquas aromaticas.