PS 9 I

• semi-solid dosage forms


  gels, creams, ointment, pastes, sticks,
• gels


  a semi-solid or semi-rigid jelly like preparation consisting of small inorganic particles or organic molecules suspended in a gelatenous base (usually with gelling agent dissolved or suspended) with a high degree of physical or chemical cross-linking. gels typically become thinner when agitated and then become firm upon standing. anaestheic gels, lubricant gels, spermicidal gels and oral gels
• types of gel bases

  hydrogels (water plus gelling agent): pectin, gelatin. organogels (organic, for water-insoluble drugs): petrolatum, mineral oil. choice of gellign agent and concentration depends on solvent system, drug and required stiffness of product.
• advantages of gels

  non-oily or greasy, invisible, lubricating, allows surface evaporation, suitable for oozing and exudative skin conditions, suitable for hairy areas of the body, water-based gels easily washed off skin, hair and clothing
• disadvantages of gels

  poor epidermal hydration compared to creams and ointments, may lead to poor drug absorption. susceptible to microbial contamination, preservatives can cause sensitization, alcohol can sting, drugs my hydrolysed more quickly in aq gels than in creams, ointments and pastes
• gelling agents examples


  xantham gum, alginate and guar gum
• process of making gels

  gel base is produced first and then the drug is added to the base.
• creams


  a semi-solid preparation containing one or more drug substances dissolved or dispersed in with an o/w or w/o emulsion base. the physical properties and potential therapeutic uses of individual creams depend upon the nature of their cream bases, the emulsifying agents used and thickening agents. 50% water
• types of creams


  anionic creams (aqueous cream APF) are incompatible with cationic drugs, because ion pairs form and reduce efficiency. cationic creams (cetrimide cream APF) incompatible with anionic drugs. non-ionic creams (cetomacrogol cream aqueous APF) yield virtually no ions, compatible with anionic and ionic drugs
• topical creams


  o/w - applied to skin, rectum and vagina, suitable for water-soluble drugs (antiseptics), easily washed off, miscible with perspiration and tissue exudates, allow water evaportion from skin and cream, suitable for wet acute skin conditions, needs antimicrobial preservative, dilute with water produces lotion. w/o - less common, suitable for local protective agents (steroids), not for water-soluble drugs, resistant to begin washed, occlusive (prevent evaporation, not for wet conditions), suitable as a barrier cream for dry skin conditions, can be diluted with oil, not water
• excipients in creams


  emulsifying agent (acacia gum, oleic acid,), thickeners/viscosity agents (carbomers and polyethylene glycol)
• manufacture of creams


  stepwise blending of inactive ingredients to produce cream base, addition of active ingredient, homogenisation, QC, packaging
• advantages of creams


  less greasy than ointments, may be invisible if spread thinly and absorbed into skin, allow some surface evaporation, suitable for oozing and exudative skin conditions, easily washed off skin, hair and clothing
• disadvantages of creams


  less epidermal hydration compared to oitments, can lead to decreased drug absorption, more susceptible to microbial contamination than ointments, preservatives may cause sensitization
• unguents


  An ointment is a smooth, semi-solid preparation with a greasy base and intended for external application to the skin or a mucous membrane, usually containing less than 20% water and more than 50% hydrocarbons, waxes or polyols as the vehicle. May be opaque or translucent, viscous or greasy. Active ingredients may be dissolved or finely divided and uniformly distributed throughout the base. May be sterile if necessary
• ointment applications


  protectant (from dehydrations), antiseptics (antibacterial or antifungal), emollient (moisturise skin), antipuritic (relieve itching), keratolytic (to soften and peel/remove hard (keratin) layer of skin), astringent (to contract and tighten loose skin)
• ointment bases


  oleaginous (hydrocarbon) bases-insoluble oils/fats, emollient effect, greasy, difficult to apply and wash (petroleum jelly and beeswax). absorption bases - w/o, absorb lots of water retains ointment consistency, not easy to wash. (hydrous lanolin) water removable/washable bases - common, o/w, easily washed off, absorb water + exudates, can be diluted, non-greasy and non-occlusive, better cosmetic appearance and compliance. water-soluble bases - no oleaginous substances, water washable, synthetic base, inert, no mould growth, mainly for incorporation of solids (PEG)
• excipients in ointments


  petrolatum, lanolin, hydrogenated vegetable oils (organic/inorganic solvents), emulsifiers, solubilisers, antioxidants, antimicrobial preservatives, pH regulators, perfumes.
• advantages of ointments


  reduced hydrolysis of drugs, easily spread and retains occlusive layer, lubricating/emollient properties, can be applied to mucosa, water resistant and persist at application site, enabling sustained release, low risk of sensitisation due to few ingredients and no preservative required, low risk of skin irritation.
• disadvantages of ointments


  greasy, difficult to remove, can stain clothes, can be uncomfortable to apply because of viscosity (large areas especially), cannot be applied to oozing or exuding site, drug release/absorption can be slow but can be improved by addition of penetration enhancers (alcohols, fatty acids)
• pastes


  very thick cream or ointment, a semi-solid preparation containing a large amount of finely divided powdered solids (25%), commonly containing thickeners (gelatin, pectin), less greasy than ointments owning to powder absorption of the base, suitable for areas of skin that need protection, remain in place longer than ointments, absorb serous discharge from skin lesions, applied thickly and can be cosmetically undesirable, unsuitable for hairy parts of body
• advantages of pastes


  protect the skin, occulsive, some can be applied to wounds as past bandages, adhere strongly to skin, high solid content may draw moisture from skin surface and reduce swelling
• disadvantages of pastes


  unsightly, may drag on skin and cause pain when applied, uncomfortable over large areas, difficult to remove from skin, hair and clothing
• how to apply cream or ointment

  wash affected areas of skin well and rinse away traces of soap or cleaner, pat skin dry don't rub, apply cream or ointment thinly and evenly taa, gently massage the cream or ointment into skin until it has all disappeared, replace the cap on tube, wash hands, unless hands are aa
• sticks


  topical medicines used on small areas are formulated as sticks with very greasy or waxy bases (lips, warts)
• stick bases examples


  no water. white wax, white petrolatum, alcohol, propylene glycol
• packaging of semi-solid dosage forms

  bottles and jars (depending on viscosity), clear or opaque, glass or plastic. tubes, plastic (HDPE, LDPE, PP, PET), aluminium (coated on inside to eliminate interactions between tube and product
• rheology of semisolids


  study of flow and deformation properties of matter, the science of how materials/fluids flow. helps analyse the portability and stability of suspensions, firmness and spreadability of creams, ointments, gels, extrusion of ointments from tube and syringibility of viscous injections
• viscosity


  dynamic viscosity (n), measure of resistance to flow or movement, the force required to make something flow, thickness, normally declines with increasing temperature. units: pascal second Pa.s or poise P. 1 Pa.s = 1000mPa.s = 10 poise, 1mPa.s = 1 centipose cP = 100 poise. kinematic viscosity = n/p (dynamic viscosity over density)
• fluidity


  a fluid propensity to flow, a measure of thinness. the reciprocal of viscosity 1/viscosity = fluidity
• shear stress


  the force applied per unit are to make a fluid material move or flow. shear stress = force applied / area . sideways movement of a layer of particles over another. more sheer stress is applied to ointments vs creams when getting them out of a jar
• shear rate


  is the rate of change of velocity (the velocity gradient) at which one layer of fluid passes over an adjacent layer. the gradient is measured perpendicularly across the stream. change from slow to fast or vice versa
• newtonian fluids


  newtonian fluids like water alcohol and other organic solvents, conform to newtons linear law of flow. as shear rate increases shear stress increases linearly, while viscosity remains the same.
• non-newtonian fluids


  suspensions, emulsions, creams, ointments have high viscosities that are not constant but vary depending on the magnitude of shear stress and shear rate and can vary over time. bingham plastics, pseudoplastics, dilants
• factors influencing viscosity


  temperature (often decreases), molecular weight (increases), capacity to complex with water through bonding (increases)
• Bingham plastics


  remain immobile because of strong interparticle forces until shear stress reaches a certain threshold (yield point) and then becomes less viscous. toothpaste and mayonnaise
• pseudoplastic


  viscosity decreases when the shear rate increases rapidly, when the shear rate ceases particles return to their normal viscosity. blood, tears, paints
• dilatants


  viscosity increases and volume increases when shear rate increases. corn starch in water. viscosity and volume increase when shear rate increases as dispersed particles become open-packed with considerable void volume, however slow movement helps particles to flow.
• thixotropics and rheopectics 


  some non-newtonian fluids change their inherit rheological properties if subjected to shear stress for a period of time and then after resting, gradually return to their former viscosities. thixotropics (gels) exhibit an overall decrease in viscosity. the temporary thinning and delay in recovery allow the product to be administered. rheopectics behave in the opposite way and exhibit an overall increase in viscosity.
• relevance of non-newtonian rheology

  important in pipes of manufacturing equipment, and packaging, rheological properties determine pourability of suspensions, the syringibility of injections, and the spreadability and adherence of creams, ointments and gels. viscosity affects rate of diffusion in semi-solids. important to know if creams or ointments thicken. pseudoplastic or thixotropic systems become thinner as it is forced through a syringe and need then return to more viscous form, which is useful for intramuscular depots (procain penicillin G) vs dilatant or rheopectic which will thicken.