Solutions part 1.PDF

1  Mixture of solute and solvent  Solid-solid, solid-liquid, solid-gas, etc.  Pharmaceutical solutions : liquid preparations that contain 1 or more chemical substance, dissolved in a suitable solvent or mixture of mutually miscible solvents...

1  Mixture of solute and solvent  Solid-solid, solid-liquid, solid-gas, etc.  Pharmaceutical solutions : liquid preparations that contain 1 or more chemical substance, dissolved in a suitable solvent or mixture of mutually miscible solvents 2  Classified according to use : Oral, otic, ophthalmic, or topical  Can also be classified based on composition : syrups, elixirs, spirits, aromatic waters, tinctures. 3  Liquid are easier to → For elderly and swallow than solids children.  Drug is → Drug uniformly homogenously distributed in distributed solution throughout the preparation  Drug in solution readily available for → Faster therapeutic absorption in GI response. 4 4  Choice of solvents depends primarily on the solubility of active ingredients in the solvent system, and suitability with the intended use  Other factors : clarity, toxicity, viscosity, compatibility with other ingredients, chemical inertness, palatability, odour, colour and economy  Most solutions – water is preferred, with auxiliary solvent to aid solvency and stability 5  Other widely used solvents : alcohol, glycerin and propylene glycol, fixed oils  Toxic solvents such as acetone, ethyl oxide, and isopropyl alcohol are recognized because of their role in extraction of chemical compounds→must ensure complete removal before final formulation (oral) 6  Alcohol USP, ethanol, ethyl alcohol ▪ C2H5OH ▪ Most useful solvent after water → for organic compounds ▪ + water = hydroalcoholic mixture – dissolves both alcohol- and water-soluble substances ▪ Non-ideal solution – contracts by about 3% ▪ OTC oral products – alcohol content limit is 0.5% for children under 6 years old ▪ For 6-12 years old, alcohol limit is 5%, for 12 years and above, limit is 10% 7  Rubbing alcohol ▪ 70% ethanol by volume + water, denaturants, colour additives, stabilizers and perfume oil ▪ Each 100mL must contain not less than 355 mg of sucrose octa-acetate or 1.4 mg denatonium benzoate. WHY? ▪ Employed as rubefacient or soothing rub ▪ Germicide, skin cleanser, vehicle 8  Isopropyl rubbing alcohol ▪ 70% by volume isopropyl alcohol, + water, with/without colour additives, stabilizers, perfume oils ▪ External use – rubefacient, soothing rub, topical vehicle 9  Glycerin USP (Glycerol) ▪ CH2OH.CHOH.CH2OH ▪ Clear, syrupy liquid, sweet taste ▪ Both water and alcohol-miscible ▪ Solvency comparable with alcohol, but slower due to its viscosity ▪ Possess preservative qualities, used as stabilizer and co-solvent ▪ Used for many internal preparations 10  Propylene Glycol ▪ Along with glycerol →polyhydric alcohols ▪ Viscous liquid, water- and alcohol-miscible ▪ Wide range of applications, substitute for glycerin 11  For oral solution, freshly boiled water from mains system (drinking water) is sufficient.  Purified water BP is also used – prepared via distillation, ion exchange and reverse osmosis process.  Purified water BP also needs to be boiled and cooled before use 12  For injections – water for injection BP  Water for the preparation of medicines for parenteral administration when water is used as vehicle (water for injections in bulk) and for dissolving or diluting substances or preparations for parenteral administration (sterilised water for injections). 13  Most pharmaceutical solutions are unsaturated with solute.  The strength of solutions are usually expressed in % w/v, % v/v.  Most solutions are prepared by simple solution of the solutes in the solvent or solvent mixture.  Heat may be desired to assist drug solubilisation. 14 14  Most contain flavour and colourings – more attractive, more palatable  Also stabilizers  Formulated in such ways that doses are delivered in convenient volumes – 5 mL (1 tsp), 10 mL, 15mL (1 tbsp)  Dropper for children 15  Dry mixture for solution ▪ Some medicinal agents, such as antibiotics have insufficient stability in aqueous solution. ▪ Dry powders or granules form for reconstitution. ▪ Dry powder mixture contains active ingredient, flavorant, colourant, buffers and others except solvent. ▪ After reconstituted, solutions remain stable for 7-14 days – sufficient for patient to complete the medication course. ▪ e.g. Penicillin V potassium for oral solution, Sodium Picosulfate Oral Powder 16  Def: concentrated aqueous preparations of sugar/sugar substitute with or without flavouring and medicinal substances  Without meds→non-medicated syrups or flavoured vehicles e.g cherry syrup, cocoa syrup, orange syrup, ora-sweet  Non medicated syrups are meant to serve as pleasant-tasting vehicles for meds in extemporaneous compounding 17  Also as means of administering disagreeable- tasting drugs  Medicated syrups : Any stable, water soluble drug may be added to flavoured syrups  Must ensure compatibility of drugs with syrup components→ some syrups are acidic, basic, or neutral  Most common medicated syrups : antitussive and antihistamine 18 A. Sugar – sucrose or non-sucrose ▪ Provides sweetness and viscosity B. Antimicrobial preservatives C. Flavouring D. Colouring E. Misc ▪ Special/co-solvents, solubilizing agents, thickeners, stabilizers 19  Sucrose – most commonly used sugar  May be replaced by other glycogenetic substances e.g sorbitol, glycerin, propylene glycol  Or, replaced with non-glycogenetic materials e.g methyl cellulose, hydroxy ethylcellulose ▪ Not hydrolyzed and absorbed in blood stream ▪ Excellent for diabetic and sugar-restricted patients ▪ Similar viscosity to sucrose-based syrup, added with flavour 20  Sucrose and alternative agents impart proper viscosity to the syrup – important in masking the taste of drugs.  Why? 21  Most syrups are 60-80% sucrose, for the desired sweetness, viscosity and also stability (compared to dilute sucrose). WHY? 22  Example: Syrup, NF (USP) or simple syrup.  85 g sucrose dissolved in water q.s ad 100 mL ▪ Requires no additional preservation if used immediately ▪ Inherently stable and growth-resistant, if properly prepared and maintained→ very concentrated, relative absence of water ▪ Slight volume of water available adds to the physical stability of the syrup. 23  Other syrups which are not as saturated as Syrup NF must be added with preservatives  Sugar substitute – solutions of polyol e.g sorbitol, glycerin  Sorbitol Solution USP – 64% by weight 24  Benzoic acid 0.1-0.2%  Sodium benzoate 0.1-0.2%  Various combi of methylparabens, propylparabens & butylparabens totalling 0.1%  Amount used varies with proportion of water, nature of other components in the syrups, and capability of preservative 25  Many flavoured with synthetic flavouring, or naturally occuring e.g volatile oils, vanillin  Must be water soluble 26  Enhance the appeal  Correlates with the flavour i.e green-mint, red-cherry  Generally water soluble, inert to other syrup components, colour stable at the pH range and light intensity subjected to the syrup during its shelf life 27  Clear, sweetened hydroalcoholic solutions intended for oral use  Usually flavoured  Non-medicated elixirs – vehicle  Less sweet and less viscous→ Less effective in taste-masking 28  Hydroalcoholic nature – better at maintaining water-soluble and alcohol-soluble components in solution  Preferred over syrup for its stability and ease of preparation  Proportion of alcohols varies widely; requires specific blend of alcohol and water  Adjunctive or co-solvent is often employed 29  Many sweetened with sucrose, higher alcoholic content→artificial sweeteners are used e.g saccharin  Also colouring agents  10-12% alcohol content – no need for preservatives  Major disadvantage – alcohol+children or non-alcohol consumers  Stored in tight, light resistant containers and protected from excessive heat 30  Linctuses are viscous oral liquids that vehicle usually contains a high proportion of Sucrose, other sugars or a suitable polyhydric alcohol or alcohols.  Linctuses are intended for use in the treatment or relief of cough, and are sipped and swallowed slowly without the addition of water. 31  Alcoholic or hydroalcoholic solutions prepared from vegetable materials or from chemical substances  They vary in prep. method, strength, alcoholic content, and intended use  Alcohol content range from ~15-80%; helps to preserve tinctures  Co-solvents e.g glycerin may be used, choice of solvents important to avoid precipitation 32  Chemical tinctures are prepared simply by dissolving the chem substance in the solvent  Storage : tightly stoppered, not exposed to excessive temperatures and protected from sunlight 33  Oral solution administered in small volumes 34  Simple liquid preparations intended for oral use.  Contain dissolved medicaments. 35  Generally, topical solutions use aqueous vehicles, while tinctures, alcoholic  Most are prepared by simple dissolution; some prepared via chemical reactions, or maceration (benzoin tincture)  Many are self-preserving  Packaged with emphasis on ease of use e.g bottle with applicator, squeeze bottle 36  A variety of medicinal substances are employed topically in the mouth  Anesthetic, anti-infective, diagnostic aid, analgesic, prophylactic, anti-inflammatory  E.g Eugenol, ystatin oral suspension, benzocaine, carbamide peroxide, saliva substitute 37  Aqueous solutions indicated for treatment of throat (gargles) & mouth (mouthwashes) generally in concentrated form  Not for swallowing & must be diluted before use. 38  Vaginal douches ▪ For irrigation cleansing of the vagina ▪ Solutions prepared from powders, liquid solutions or liq. Concentrates ▪ Components:- ▪ Boric acid/sodium borate, astringents (potassium, alum, aluminium alum, zinc sulfate), antimicrobials, NH4+ compounds, detergents, oxidizing agents, salts, aromatics 39  Retention enemas ▪ Solutions administered rectally for local or systemic effects ▪ Minimized effect of gastric administration→ therapeutic levels achieved ~30 mins 40  Evacuation enemas ▪ Used to clean the bowels ▪ Solutions of sodium phosphate and sodium biphosphate, glycerin and docusate potassium, and light mineral oil ▪ Works in 5-10 mins ▪ Commercial disposable plastic squeeze bottles 41  Used to cleanse part of the body such as eye, urinary bladder, or open wounds 42  Aromatic waters ▪ Clear, aqueous solutions saturated with volatile oils or other volatile substances ▪ e.g orange flower oil, rose oil, peppermint oil ▪ Used for perfuming and flavouring 43  Diluted acids ▪ Aq. solution, diluting concentrated acid with purified water ▪ Strength expressed as % w/v ▪ E.g diluted acetic acid 6% w/v – antibacterial effects, used as surgical dressing solution, bladder irrigation (0.25% w/), spermatocidal 44  Spirits ▪ Alcoholic or hydroalcoholic solutions of volatile substaces ▪ > 60% alcohol ▪ Allows greater concentration of oil and volatile substances compared to water ▪ Used as flavouring agent and for the therapeutic value of the dissolved aromatic oil 45  Taken orally (mixed with portions of water), applied externally, or used by inhalation  Prepared by simple solution, maceration, or distillation  e.g aromatic ammonia spirit, camphor spirit, compound orange spirit, peppermint spirit 46  Liniments ▪ Alcoholic or oleaginous solutions/emulsions of med substances ▪ Intended to be rubbed on the skin ▪ Alcohol/hydroalcoholic vehicle – when rubefacient, counterirritant, or penetrating action required 47 ▪ Oleaginous liniments ▪ Less irritating than alcoholic ▪ Solvents – fixed oil e.g almond, peanut, sesame, or volatile substances such as turpentine, or combi of both ▪ Employed primarily for massage ▪ Vehicle for liniments chosen based on intended action and solubility of desired components ▪ Label – for external use only, and if in suspension form, instruction to shake thoroughly ▪ Stored in tight containers ▪ Prepared in the same manner as solutions, emulsions, or suspensions 48  Liq. preparation composed of pyroxylin dissolved in solvent mixture composed of alcohol and ether with/without med substance  Pyroxylin ▪ Soluble gun cotton, collodion cotton ▪ Product of cotton mixed with HNO3 and H2SO4 ▪ Consists of cellulose tetranitrate 49 ▪ 1 part pyroxlin – soluble in 25 parts of 3:1 ether:alcohol ▪ Also soluble in acetone and glacial acetic acid, flammable ▪ Intended for external use, applied to the skin, evaporates, leaving a film of pyroxylin and/or medicated substance ▪ USP preparati0ns : collodion, flexible collodion, salicylic acid collodion 50