COMPOUNDING GELS

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COMPOUNDING GELS

• Dr Tabbakhian
• Isfahn University of Medical Science

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COMPOUNDING GELS

• Definitions/Types
• Classification Systems
• Applications
• Composition
• Preparation
• Physicochemical Considerations

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COMPOUNDING GELS

• Quality Control
• Packaging/Storage/Labeling
• Stability
• Patient Counseling
• Sample Formulations

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GELS

• Are semisolid systems consisting of suspensions
  made up of either small inorganic particles or
  large organic molecules interpenetrated by a
  liquidUSP/NF

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DEFINITION-GELS

• Semisolid systems consisting of dispersions of
  small or large molecules in an aqueous liquid
  vehicle rendered jelly-like through the addition
  of a gelling agent.
• Semirigid systems in which the movement of the
  dispersing medium is restricted by an interlacing
  network of particles or solvated macromolecules
  of the dispersed phase.

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TYPES OF GELS

• Single Phase
• gels in which the macromolecules are uniformly
  distributed throughout a liquid with no apparent
  boundaries between the dispersed macromolecules
  and the liquid.
• Usually involve organics
• Two Phase
• when the gel mass consists of floccules of small
  distinct particles
• usually involve inorganics

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CLASSIFICATION SYSTEM I

• INORGANIC
• Usually 2 phase systems
• Aluminum hydroxide gel, Bentonite magma
• ORGANIC
• Usually 1 phase systems
• Carbomer, Tragacanth
• HYDROGELS
• Contain water
• Silica, bentonite, pectin, methylcellulose

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CLASSIFICATION SYSTEM II

• ORGANOGELS
• Hydrocarbon Type
• Petrolatum, Mineral oil/Polyethylene gel,
  Plastibase
• Animal/Vegetable fats
• Lard, Cocoa butter
• Hydrophilic Organogels
• Carbowax bases, PEG Ointment

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CLASSIFICATION SYSTEM II

• HYDROGELS
• Organic Hydrogels
• Pectin paste, Tragacanth jelly
• Natural and Synthetic Gums
• Methylcellulose, Sodim CMC, Pluronics
• Inorganic Hydrogels
• Bentonite gel, Veegum

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APPLICATIONS

• Oral
• Topical
• Intranasal
• Vaginal
• Rectal

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COMPOSITION
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GEL COMPOSITION

• Gelling agent
• Water
• Cosolvents
• Preservatives
• Stabilizers

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PREPARATION METHODS

• Carbomer resins
• Bentonite
• Gelatin
• Tragacanth
• Alginic Acid
• Sodium CMC

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PREPARATION METHODS

• Silicon dioxide, Colloidal
• Methylcellulose
• Pluronic
• Polyvinyl alcohol

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GENERAL TECHNIQUES

• Active drug before/after gelling
• Plastic bag
• Use of wetting/dispersing agent
• Full hydrationgt up to 24 hours

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PHYSICOCHEMICAL CONSIDERATIONS

• Syneresis
• Swelling
• Imbibition
• Thixotropy

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PHENOMENA ASSOCIATED WITH GELS

• Syneresis
• when the interaction between particles of the
  dispersed phase becomes so great that on
  standing, the dispersing medium is squeezed out
  in droplets and the gel shrinks.
• Swelling
• the taking up of liquid by a gel with an increase
  in volume.

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PHENOMENA ASSOCIATED WITH GELS

• Imbibition
• the taking up of a certain amount of liquid
  without a measurable increase in volume.
• Thixotropy
• a reversible gel-sol formation with no change in
  volume or temperature.

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GELATION

• As a hot, colloidal dispersion of gelatin cools,
  the gelatin macromolecules lose kinetic energy.
• With a reduction of kinetic energy or thermal
  agitation, the gelatin macromolecules are
  associated through a dipole-dipole interaction
  into elongated or threadlike aggregates.

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GELATION

• The size of these association chains increases to
  the extent that the dispersing medium is held in
  the interstices among the interlacing network of
  gelatin macromolecules, and the viscosity
  increases to that of a semisolid.
• Gelatin, agar, pectin, Irish moss, pectin,
  tragacanth--form gels by this mechanism

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PROPERTIES OF GELLING AGENTS

• Alginic acid --
• Bentonite pH gt6
• Carbomer pH 4.5-11
• CMC pH 2-10
• CMC Sod pH 5-10
• Colloidal Silicon Dioxide pH 7.5-10.7
• Veegum pH gt3.5

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PROPERTIES OF GELLING AGENTS

• Methylcellulose pH 3-11
• Plastibase/Jelene
• Poloxamer/Pluronic
• Povidone
• Propylene Glycol Alginate pH 3-6
• Sodium Alginate pH 4-10
• Tragacanth pH 4-8

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QUALITY CONTROL

• Appearance
• Uniformity
• Weight/Volume
• Viscosity
• Clarity
• pH
• Others

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PACKGING/STORAGE/LABELING

• Tight containers
• Room or Refrigerated Temperatures, as appropriate
• Prior to use.store in tight containers.

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STABILITY

• Physical Stability
• Shrinkage
• Separation of liquid from the gel
• Discoloration
• Microbial Stability
• BUD Unless otherwise documented, 14 days when
  stored in a refrigerator. USP

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PATIENT COUNSELING

• Proper application
• Proper storage
• Keep tightly closed

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SAMPLE FORMULATIONS
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EXAMPLE PREPARATIONS

• Rx
• Ephedrine sulfate 10 g
• Tragacanth 10 g
• Methyl salicylate 0.1 mL
• Eucalyptol 1 mL
• Pine needle oil 0.1 mL
• Glycerin 150 g
• Purified water 830 mL

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STARCH GLYCERITE

• Rx
• Starch 100 g
• Benzoic acid 2 g
• Purified water 200 g
• Glycerin 700 g

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BENTONITE MAGMA

• Bentonite 50 g
• Purified Water qs 1000 mL

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POLOXAMER GEL BASE

• Poloxamer F127 20-50 g
• Potassium sorbate 200 mg
• Purified water/buffer qs 100 mL

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PLO GELS

• Rx
• Active drug
• LecithinIsopropyl Palmitate 11 22 mL
• Pluronic F127 20 Solution qs 100 mL

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LIQUID-SOLID EMULSION GEL-DRUG RELEASE

• GELATIN SOLUTION
• Gelatin, 200 bloom 8 g
• Phosphate buffer (pH 7) qs 40 mL
• GEL PRODUCT
• Gelatin Solution 40 mL
• Long-chain alcohol 10 g

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LUBRICATING JELLY

• Methylcellulose 4000 cps 0.8
• Carbomer 934 0.24
• Propylene glycol 16.7
• Methylparaben 0.015
• Sodium hydroxide qs pH 7
• Purified water qs 100

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CLEAR AQUEOUS GEL WITH DIMETHICONE

• Purified water 59.8
• Carbomer 934 0.5
• Triethanolamine 1.2
• Glycerin 34.2
• Propylene glycol 2.0
• Dimethicone copolyol 2.3
• Sodium hydroxide 1 12 mL

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Methylcellulose gels

• Methylcellulose 1500 cps 1-5
• Purified water qs 100

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ESTRADIOL TOPICAL GEL

• Estradiol 50 mg
• 70 Isopropyl alcohol 71 mL
• Carbomer 940 500 mg
• Triethanolamine 670 mg
• Purified water 28 mL

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ESTRADIOL VAGINAL GEL

• Estradiol 200 mg
• Polysorbate 80 1 g
• Methylcellulose 2 gel 99 g

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PIROXICAM 0.5 IN AN ALCOHOLIC GEL

• Hydroxypropylcellulose 1.75 g
• 70 Isopropyl alcohol 98.25 mL
• Propylene glycol 4.1 mL
• Polysorbate 80 1.7 mL
• Piroxicam 20 mg capsules 25 capsules

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VANCOMYCIN GEL

• Vancomycin 500 mg
• Aspartame 200 mg
• Flavor qs
• Sodium benzoate 200 mg
• Methylcellulose 2 gel 100 mL

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SCOPOLAMINE HBR 0.25 MG/0.1 ML TOPICAL GEL

• Scopolamine HBr 250 mg
• Soy lecithin/Isopropyl
  palmitate solution 25 mL
• Buffer solution (pH 5) 2.5 mL
• Poloxamer F127 20 gel qs 100 mL