Pharmaceutics I Lecture (3) Internal Aqueous Solutions PDF

Pharmaceutics I Lecture (3) Internal Aqueous Solutions Dr. Doaa Hamdy Shakshak, Phd. Lecturer of Pharmaceutics and Industrial Pharmacy 1  Pharmaceutical Solutions Sweet &/or Viscid Aqueous...

Pharmaceutics I Lecture (3) Internal Aqueous Solutions Dr. Doaa Hamdy Shakshak, Phd. Lecturer of Pharmaceutics and Industrial Pharmacy 1  Pharmaceutical Solutions Sweet &/or Viscid Aqueous Nonaqueous Water Alcohols, Oils Sweet and viscous Contain sugars 1. Oral solutions Liquid paraffin Of special interest ether and/or gums 2. Douches 1. Elixirs 1. Syrups 3. Enemas 2. Spirits 2. Honeys 4. Gargles 3. Collodions 3. Mucilages 5. Mouthwashes 4. Glycerites 4. Jellies 6. Nasal solutions 5. Liniments 5. Juices 7. Otic solutions 6. Oleo Vitamins 8- Aromatic water  Oral Internal Pharmaceutical solutions The pharmacist may be asked to: Dispense a Dilute the commercially concentration of a prepared oral solution (pediatric solution. form of an adult product). Reconstitution of a Extemporaneously dry powder compound an oral mixture. solution from bulk components. Knowledge of the solubility and stability of the medicinal agents and the solvents employed in the commercial products → inform the patient of mixing the solution with juice, milk, or other beverages upon administration. 3 1- Examples of solutions of pharmaceutical interest A- Oral Rehydration Solutions: Used in diarrhea Allow the diarrhea to proceed and to replace the fluid and electrolytes that are lost to prevent dehydration Contains 45 mEq Na+, 20 mEq K+, 35 mEq Cl-, 30 mEq citrate, and 25 g of dextrose per liter. Glucose is Glucose active Sodium actively transport is absorption This promotes absorbed from coupled with promotes anion water the small Na+ absorption. absorption absorption. intestine. 4 B- Oral Colonic Lavage Solution: - Used for the preparation of the bowel for procedures such as a colonoscopy. Polyethylene Glycol 3350 236.00 g Acts as an osmotic Sodium Sulfate 22.76 g agent within the GIT Sodium Bicarbonate 6.74 g Sodium Chloride 5.86 g Potassium Chloride 2.97 g The balanced electrolyte concentration results in virtually no net absorption or secretion of ions. Thus, a large volume of this solution can be administered without a significant change in electrolyte balance. 5 C- Magnesium citrate oral solution (or Citrate of Magnesia): Magnesium Carbonate........15 g Anhydrous Citric Acid.........27.4 g Syrup...................... 60 mL Talc....................... 5 g Lemon Oil.................. 0.1 mL Potassium Bicarbonate......... 2.5 g Purified Water, sufficient quantity, to make................ 350 mL The solution is prepared by: 1- Reacting magnesium carbonate with an excess of citric acid, MgCO3+citric acid → Mg citrate+ carbonic acid + citric acid 2- Flavoring and sweetening the solution with lemon oil and syrup, filtering with talc 3- Carbonating it by the addition of potassium or sodium bicarbonate. 6  Impossible to close Immediate and the bottle in time to Powder violent, prevent the loss of CO2 or solution Carbonation Delay the effervescence resulting Tablet from bicarbonate contact with citric acid. 4- Packaging: same type of bottles as soft drink carbonated beverages (300ml). Since it is carbonated, it loses some of its character if allowed to stand for a period of time after the container has been opened. 5- Storage: In air tight containers in a cold place, preferably in a refrigerator 6- Uses: as a saline cathartic, with the citric acid, lemon oil, syrup, carbonation and the low temperature of the refrigerated solution → patient’s acceptance of the large volume of medication. 7 D) Dry mixtures for solution (Powder for reconstitution) Substances which have insufficient stability in aqueous solution for extended shelf-life periods (antibiotics). Dry mixtures: - Drug Reconstituted by Stable when stored in the -Flavorant refrigerator (7 to 14 days). -Colorant solvent The remaining should be -Buffers discarded. Examples 1- Cloxacillin Sodium for Oral Solution. 2- Nafcillin Sodium for Oral Solution. 3- Oxacilln Sodium for Oral Solution. 4- Penicillin V Potassium for Oral Solution. 5- Potassium Chloride for Oral Solution, a potassium supplement. 8  Sweet or other viscid aqueous solutions Syrups Mucilage Jellies Juices Sweetness & viscosity is given by: 1- Sugars eg. Sucrose 2- Polyols eg. Glycerol, sorbitol ( several –OH groups) 3-Polysaccharide (gums) eg. Gelatin, acacia, chitosan 9  I. Syrups Conc. solution of sugars (eg. Sucrose) in water or other aq. liquid Flavored syrup Simple syrup Medicated syrup Doesn’t contain drug Water is used alone Contain drug but aromatic or flavored substance Simple Syrup concentration ( BP 66.7%w/w USP 85%w/v) Microbial growth (high conc. If diluted retard microorganism Concentration of growth) syrup approaches but not reach the saturation point Crystallization of If saturated sucrose occurs on changing temp. N.B.: The specific gravity of syrup (1.313) is very important to 10 identify its concentration (determined by saccharometer). Uses of syrup - Mask bitter and saline taste of drugs - Useful for children as it has sweet taste & contain little or no alcohol - Antitussive (syrups have soothing effect on irritated tissue of the throat) Preparation of syrups Solution with Solution with Percolation aid of heat agitation of sucrose Glycerin or sorbitol (polyols) may be added to: 1- Prevent crystallization (atoms gather to make tightly bonded or connected groupos) of sucrose→ polyols like glycerol forms H- bonding with water molecules and sugar molecules preventing formation of compact tightly bonded sugar molecules together. 2- Increase the solubility of other drugs (Co-solvents). A) Solution with heat: Add sufficient purified water to make the desired weight or volume Heat Strain It is rapid method but not used for: Volatile substance (flavored substances). Substance unstable in heat (thermolabile) Sucrose → dextrose + levulose Excessive heating in the preparation (monosaccharides). of syrup must be avoided → To Invert sugar prevent inversion of sucrose (this is fast in acid medium). 12  Invert sugar properties: Overheating More Tend to darken cause fermentable. in colour. carmelization (yellow color) Inverted syrup when added to syrup. 1-Prevent oxidation of drug (levulose is a reducing sugar). 2- Prevent crystallization of sucrose. 3- Sweeter taste Preparation of inverted syrup: neutralize excess (95% of sucrose Add HCl + syrup Heat HCl by CaCO3 or Strain is inverted) NaHCO3 N.B. Acacia Syrup is an example of syrup prepared by soln with heat and used as flavored vehicle. 13 B) Agitation without heat: Sucrose + water in bottle of twice size (allow active agitation & dissolution)→ shake to dissolve Suitable for To avoid heat volatile and induced inversion thermolabile of sucrose. substances. Used for codeine In diabetic phosphate syrup patients, sorbitol is (cough syrup) used instead of sucrose 14 C) Percolation: Water + Bed of coarse granular sucrose A piece of cotton is placed in the neck of the percolator to prevent the passage of undissolved sucrose Syrup Eg. Syrup USP Coarse crystalline sucrose The cotton must not be The percolator should be must be used to avoid pressed too tight (slow cylindrical with a conical formation of compact flow) or too loose (fast base at the lower orifice mass through which the flow). 16 liquid can not pass. Preservation & storage of syrups : If conc. is less than saturation → mould growth (needs preservative e.g. Glycerol, benzoic acid, sod benzoate, methyl paraben). The amount of preservative to be added is proportional to the amount of free water. Store in dry bottle and in cool dark place (not above 25 ᵒc as suggested by USP) Alcohol is frequently used to assist the dissolution of alcohol- soluble ingredients (flavors) but normally it is not present in the final product in amounts sufficient for preservation (15 to 20%). 17 Sucrose alternatives in syrups Used in syrup Contains 70% containing acid w/v dextrose. A- Dextrose based syrups: to avoid the inversion and Dextrose dissolves more discoloration on slowly than using sucrose. sucrose. Less viscous and Glycerin is used less sweet than B- Sorbitol- based syrups: simple syrup. as preservative. Sorbitol is a hexahydric alcohol made by hydrogenation of glucose. Used in conc of 70% w/w in water. Sorbitol advantages over sucrose: Although glycogenic-like sucrose( i.e. Converted Chemically Not cause into glucose in the Not support stable & not dental carries. body), however it is not mould growth. affected by absorbed rapidly so not heat. cause hyperglycemia. 18 C-Artificial syrup (non-nutritive syrup) Eg. Cyclamate, aspartame, saccharin Used for: 1- diabetic patients 2- persons regulating their sugar/caloric intake First they used glycerin & propylene glycol but they are glycogenic substances ( converted to glucose in body) Example of non-nutritive syrup (diabetic simple syrup) Sodium carboxymethyl cellulose 1.5% (↑viscosity) 0.6% saccharin Na Compound sodium cyclamate solution Preservative q.s 6% cyclamate Na Purified water q.s. Studies showed that cyclamate & saccharin Aspartame (200 times sweeter than sucrose), could produce cancer in animals, thus was is being used now in many commercial removed from a wide variety of products. preparations as the sweetening agent. 19  II. Mucilage III. Jelly Nature Thick viscid, adhesive liquid Semisolid to thick viscous fluids Composition 1- Dispersing gum in water Matrix contain high water proportion. 2- Extracting mucilaginous Prepared from same gums as substances from vegetables mucilage but has jelly-like consistency Preparation Acacia (35% in water) & Prepared in water from acacia, tragacanth (6%) tragacanth, gelatin, carboxy methyl cellulose Preservation Liable to decomposition & should Preservatives e.G. Methyl p- be used immediately unless a hydroxybenzoate is used because preservative eg benzoic acid is jellies are prone to microbial added. contamination Uses Suspending agents for insoluble -Lubricant for surgical gloves, rectal substances in liquids. thermometer & catheter. Their character and viscosity - Topical anesthetic (e.g. Lidocaine HCl prevent immediate sedimentation jelly). of insoluble substances.  IV. JUICES They are prepared from fresh ripe fruit, it is aqueous in nature, and is used in making syrups Grind Pectinase Pectins are destroyed by Ripe fruit Turbid juice enzyme Clear juice Pectins are complex polysaccharides that are present in the cell walls and hold the cells together N.B. Artificial flavors like vanillin replace e.g. Cherry juice and natural fruit juice as it Raspberry juice are is more stable and used as flavored easier to be vehicle. incorporated into the final pharmaceutical form. 22  Aqueous Pharmaceutical Solutions Aromatic waters (medicated waters) It is clear saturated aqueous solution of volatile oils or other aromatic or volatile substances that can be used as flavored vehicle Distillation Methods of preparation Their odors and tastes are similar to the Solution volatile substances from which they are prepared Alternate solution Solubilizing It should be free from agent empyreumatic (smoke- like) and other foreign odors. Dilution N.B. Fixed oils are the opposite of volatile oils. 23 They are non-volatile and usually of vegetable origin  A-Distillation: (steam distillation ) It is slow and expensive but it is the most satisfactory method. Eg. Strong rose water NF The drua is ground Drug :Distillate ratio & mixed with Fresh drugs: from 1:2 to 2:1 sufficient quantity of Dried drugs: e.g cinnamon, purified H20 in anise and caraway (1:10). distillation unit. Dried leaf drug:- e.g peppermint (3:10). The drug shouldn’t be exposed to direct heat to avoid carbonized Excess oil in the substance odor of distillate is removed by distilled aromatic filtration or through water. essential oil outlet Cohobation It is the process in which This process is used Double distilled, triple the distillate is returned when the volatile distilled or quadruple several times to the still principle present in distilled are commercial with fresh portions of small quantities (e.G terms to describe the drug. orange flower and rose number of re- 24 waters). distillation.  B- Solution Method eg. Chloroform water O W Shake Filter, complete volume 2 gm or 2 ml of the volatile to1000ml by purified H2O Set aside for 12 hrs substance to ensure saturation. + 1000ml of purified water. The filter paper must be wet: A large excess of solute is - To prevent the passage of used (2 gm per liter) to excess oil into the filtrate obtain a saturated solution. - To eliminate absorption of the dissolved aromatics by the filter. Disadvantages (difficulties) (1) Clarification (2) Time-consuming (12 hrs) 25 C- Alternate Solution process Used for the preparation of Peppermint water (using Talc): 1L purified water Mix peppermint oil Filter through wet with 15 gm talc. filter paper agitate for 10 min. Role of talc: - Distributing agent: Increases the surface area of volatile substance to ensure rapid saturation of water (time saving). - Clarification and filter aid: Act as filter bed producing clear solution. D- Using solubilizing agents: e.g Polysorbate (tween) 80 or 20 Susceptible to mould growth and bad oily taste (in conc. >2%) E- Dilution process Concentrates that should to be diluted with an appropriate volume of water when needed to avoid the difficulties that arise in the clarification of aromatic waters. Eg. peppermint, cinnamon and anise waters Dissolve 20 ml oil in 600 ml Shake Dilute the concentrate (1part) 90% ethanol + water to 1000 by 39 times its volume water ml + 50 gm talc Filter (1+39) Producing aromatic water which contains less than 1.5% alcohol. Disadvantage: Aromatic water prepared by these methods are inferior in quality to those prepared by distillation or solution. 27 Disadvantages of aromatic water: If they become cloudy they should be discarded If soluble salt is added, it causes salting out of the oil (incompatibility) (to solve this problem part of aromatic water is replaced by purified water). Deteriorate easily due to volatilization, decomposition or mould growth (should be made in small quantities and protected from light and heat by storing in air tight and light resistant containers in a cool place). No preservatives are allowed to be N.B.: Natural volatile oil is now replaced by added as they would interfere with synthetic one e.g. imitation otto rose (contains their therapeutic properties. phenyl ethyl alcohol , rhodinol) 28 29