Oral Solutions, Syrups, & Elixirs

Physicochemically: Solution may be prepared from any combination of solid, liquid, & gas. Pharmaceutically: Solution are liquid pharmaceutical formulations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents.

Solutions are classified based on their use: Oral solution; Otic solution; Ophthalmic solution; Topical solution; Injection solution. Solutions are classified based on their formulation: Syrups; Elixirs; Spirits; Aromatic water; Tincture or fluid extract;

Oral solution contains: ………………; ……………………………… (i.e. preservatives, antioxidants,..etc). In compounding pharmaceutical solution, pharmacist must be aware of: ……………… of the solute; ……………… of common pharmaceutical solvents; ………………with regard to all components of formulation;

Dissolution & Solubility I. The Process of Dissolution & Kinetic theory of Matter: In solid state of matter (condensed phase) the thermal motions of molecules or atoms are reduced to the minimum, so that the ………………forces result in a coherent masses of molecules (TD organization). In gaseous phases the molecules move ……………… within the container, because they have very weak intermolecular bonds.

In liquid condensed systems the thermal motion of molecules are > than that of the solids but are < than that of the gas. This is due to the nature of the ………………between the molecules of the liquid, which are stronger than that of the gas but weaker than that of the solid. Therefore: Liquid has ………………structure; The liquid tends to contain a small amount of free spaces or volumes called holes; When the solute dissolves in the liquid the ↑ in volume is < than the expected.

G = H – T.S eq. 1 G, is the variation in the free energy H, is the variation in the enthalpy S, is the variation in the entropy T, is the thermodynamic temperature of the system. Therefore: If H is (-), the transformation is called exothermic (spontaneous dissolution). If H is (+), the transformation is called endothermic (non-spontaneous dissolution). If H is 0, the transformation is in equilibrium (ideal solution).

S is usually (+) for any process like dissolution. In real solutions a change in the enthalpy will therefore accompany the dissolution. From equation 1 we fined that the dissolution will occur if H is either negative or if it is positive but < than T. S.

H = Hcr + Hsolv eq. 2 Hcr is the absorbed heat when the crystalline molecule were separated by an infinite distance against the effect of their intermolecular attractive forces. Hsolv is the enthalpy of solvation & it is the absorbed heat when the solute molecules are immersed in the solvent. Hcr is always (+). Hsolv is always (-). But in must cases Hcr > Hsolv So H is usually (+) & the process is endothermic.

II. Solubility G is the required energy to perform a work. G = 0 at equilibrium. Solution achieved when equilibrium is established between dissolved & un-dissolved solute in a dissolution process is termed a saturated solution. Solubility is the maximum amount of solute that can be dissolved in certain solvent at constant temperature & pressure.

Types of interactions between molecules & Solubility: Dipole-dipole interactions (Van der Walals forces); Ion-dipole & H-bonds. H-bonds are very important because of small size & large electrostatic field. Hydrogen bonds involve strongly electronigative atoms (i.e. O2, Cl2, F2,..etc.)

When solute dissolves: The ……………… (attractive forces) between: the own molecules of solute & the own molecules of solvent are ……………… ……………… (attractive forces) between: molecules of solute & solvents.

Methods for increasing drug solubility: Selection of ………………; Selection of ………………of the medicinal agent; ………………; ………………………………, of the solvent; ………………: I2 + KI  K+I-3 solubility of I2 is 1g/3000mL, while solubility of KI-3 is 2g/100mL

………………: Most medicinal agents need heat for dissolution (………………); Few drugs exhibit a decrease in solubility with a rise in temperature (………………). Variation of chemical & physical properties of both ……………… & ………………such as: Pressure, acidity or basicity of the solution. The solubility of a pure chemical at given P & T is constant but its dissolution rate depends on factors such as: Particle size & Asp of the solute & agitation during dissolution process.

Steps of solubility determination: ………………………………of the drug at given T & P; Analyze ………………………………the amount of drug present in a given amount of solution; Calculation of ………………………………. Method of expressing solubility when exact solubility is unknown (USP method):

Table 1 & 2

There is no exact rule for predicting exact solubility of a drug in a specific solvent. The most frequently used rule is: Like Dissolve Like so, Organic compounds (bases & acids) are more soluble in alcohol than in water. Pharmaceutical scientist can estimate general solubility of a drug based on its chemical structure such as: ………………in organic compounds (i.e. polar groups increase water solubility); ………………;

General rules of solubility for Inorganic Molecules:

General rules of solubility for Organic Molecules: Molecules with ………………… functional group are water-soluble to a total length of …………………; Branched chain molecules are ………………… than ………………… isomers; ………………… decrease solubility; ………………… between solvent & drug results in ↑ of solubility. How pharmacists select pharmaceutical solvent? …………………; ………………… with drug & ………………… in the formulation; …………………(i.e. palatability, clarity and smell).

Water is the most used solvent in pharmaceutics; Some solvents for oral preparations: I. Alcohol, USP (Ethyl Alcohol, Ethanol, CH3CH2OH) Alcohol, USP, is ………………… CH3CH2OH when determined at 15.56 °C The above T is the ………………… for alcohol determination. II. Dehydrated Alcohol, USP, contains ………………… CH3CH2OH. The above alcohol is used for ………………… when anhydrous conditions are desired.

Alcohol is considered as pharmaceutical ………………… Alcohol has ………………… activity which make it an acceptable preservative. Alcohol is used in combination with …………………, …………………, & ………………… to ↓ the amount of alcohol due to its …………………. The ………………… of alcohol ………………… its use in OTC. The FDA regulation for OTC product intended for pediatric use: < 6 years [ethanol content …………………] 6 – 12 years [ethanol content …………………] > 12 years [ethanol content …………………]

III. Diluted Alcohol, NF Diluted alcohol, NF, is prepared by mixing equal volumes of Alcohol, USP, & Purified water, The sum of the two volumes is 3% less than the expected. [Alcohol] of 50 ml of alcohol 96 % + 50 ml of water is 49%. 96 alcohol : 100 ml solution X1 : 50 ml X1 = 50 . 96 = 47.3 ml of alcohol in 50 ml of solution. 100 Thus, mixing 50 ml of alcohol, USP + 50 ml water we will have 97 ml of final volume with the following exact concentration: 47.3 ml alcohol : 97 ml solution X2 : 100 ml of solution X2 = 47,3 . 100 = 49.2 % v/v. 97

Glycerin, USP (Glycerol), CH2OHCH(OH)CH2OH Glycerin is a ………………… with a ………………… ………………… & ………………… miscible. It has ………………… capacity comparable with alcohol. Its high viscosity (η) slow its ………………… capacity, so, heat will ↓ η & ↑ dissolving capacity of glycerol. It has ………………… capacity. It is used in many ………………… formulations.

Propylene Glycol, USP, CH3CH(OH)CH2OH ………………… & ………………… liquid. ………………… & ………………… miscible . Has ………………… properties. Its ………………… properties are similar to glycerin. It ………………… glycerin in many modern formulations.

I. Drinkable or Tap water; II. Purified water, USP, H2O Characteristics of drinkable or tap water: …………………, ………………… and ………………… liquid; Total ………………… is ≤ 0.1 %w/v; …………………; ……………………. Drinkable water can not be used in ……………………. because: Chemical ……………………. (i.e. precipitation, discoloration, & effervescence). It is used only for ……………………. & cleaning of pharmaceutical machinery.

Types of Purified water: Purified water, USP, H2O: Total solid content is ≤ 0.001 %w/v (1mg/100ml). It is used for cosmetic, & pharmaceutical preparation Types of Purified water: I. ……………………. water (ion-exchange method); II. ……………………. water; …………………….(RO) water. Purified water is prepared from water complying with the federal environmental protection agency with respect to drinking water.

Demineralized or De-ionized water This water is obtained ……………………. method. Ion-exchange equipment involves the use of water insoluble resins: ……………………. or acid exchanger resin: H-Resin + M+ + X- + H2O M-Resin + H + + X- + H2O ……………………. or base exchanger resin: Resin-NH2 + H+ + X- + H2O Resin-NH2.HX + H2O

II. Reverse Osmosis (RO): Industrially known as cross-flow or; Known as Tangential flow membrane filtration:

A pressurized stream of water is passed parallel to the inner side of a filter membrane core; A ……………………. of the ……………………. water, or influent, permeates the membrane as filtrate; While the balance of the water sweeps tangentially along the membrane; This last one exit the system without being filtered; The filtered portion is called …………………….(purified); The non-filtered portion is called …………………….(rejected);

In Reveres Osmosis the flow is from the high concentrated solution to the less concentrated.

Removing of particles depends on pore size of cross-flow filter membrane: ……………………. removes bacteria (0.1 – 2 µm); ……………………. removes viruses (0.01 – 0.1 µm); ……………………. removes organic compounds MW 300 – 1000 (0.001 – 0.01 µm); RO removes virtually all viruses, bacteria, pyrogens, organic molecules & 90-99% of all ions (≤ 0.001 µm).

III. Distilled water The first portion of the distilled water (10 – 20%) must be discharged. The last 10% of the original water for distillation must be discharged.

Preparation of Solution Most Pharmaceutical solutions are unsaturated. Thus, the amount of ……………………. than the ……………………. of the volume of solvent employed. Methods of expressing strength of pharmaceutical solutions: Table 6-4

Heat use must not exceed the ……………………. due to: Pharmacists may employ the following methods to increase the dissolution rate of a drug: …………………….; Use of …………………….; Rigorous …………………….. Increase of rate of dissolution is important since most pharmaceutical solutions are unsaturated. Heat use must not exceed the ……………………. due to: Drug …………………….; Presence of ……………………., or solvents, or additives; ……………………. dissolution of certain drugs (i.e. Ca(OH)2)

Water solubility of calcium hydroxide topical solution, USP: 140 mg/100 ml at 25 °C; 170 mg/100 ml at 15 °C. The storage temperature ……………………. the [] of the resultant solution. Most oral solutions are prepared by ……………………. ……………………. of solutes in the solvent or solvent mixtures. Industrially very large ……………………. are used. If heat is required, a ……………………. controlled mixers tanks may be utilized.

Oral Solutions & Preparations for Oral Solution Oral solution usually contains: Flavorants & Colorants; Sweetening agents; Stabilizers for chemical & physical stability (i.e. antioxidants); Preservatives to prevent microbial growth (i.e. mp & pp);

Compounding pharmacists must be aware of: Chemical & physical incompatibilities between the various components of solution. These ……………………. results in drug ……………………. & loss of potency. Esters of parahydroxybenzoic acid (i.e. mp, ep, pp …etc.) have the ……………………. to ……………………. into certain ……………………. oils. This partition ↓ their preservation efficacy.

Tools for oral solution administrations: Tea spoonful = 5 mL; Table spoonful = 15 mL; …………………….; …………………….. Few solutions have large doses (i.e. Mg citrate oral solution, USP, with actual dose of 200 mL).

Dry Mixtures for Solution For drugs (i.e. antibiotics) that have insufficient stability in water to meet ……………………. shelf-life periods. Manufacturers provide these ……………………. in dry powder or granules ready for …………………….. The dry mixture contains all ……………………. including ……………………., ……………………., sweeteners, … etc. Once they are reconstituted with addition of solvent/s, the ……………………. is ……………………. from 7 to 14 days depending on drug & storage conditions. Patient must be ……………………. to ……………………. the remaining part of formulation after the patient completes his course therapy.

Pharmacist must advise patient on: Oral Solutions Pharmacist must advise patient on: …………………….; …………………….. Pharmacists must know: Characteristics of solvent used in the formulation to: Advise patient about mixing formulation with Juice, milk or other beverages. Product label & Package insert must contain ……………………. about ……………………. used in formulation.

Table 6-8

Oral Rehydration Solutions Diarrhea is a normal ……………………. body ……………………. against noxious or toxic substance e.g., Rotavirus, E. coli. Diarrhea is characterized by an ↑ frequency of loose watery stools. During diarrhea the ……………………. in smooth intestine largely exceed the capacity of large intestine to reabsorb it. Diarrhea can lead to dehydration & ultimately death, particularly in pediatric & elderly Patients. Over 5 million children < 4 years age die due to diarrhea each year worldwide.

Loss of fluid during diarrhea results in loss of Na+, K+ & HCO3 -. Sever loss in the above ions results in: ……………………. shock; …………………….; ……………………., which if continuous lead to malnutrition. Treatment approach of diarrhea: Allow diarrhea to ……………………. & ……………………. it quickly. Replace the lost fluid & electrolytes with an oral rehydration solution to avoid dehydration. These are OTC products effective in patients with mild volume depilation of 5 – 10% of body weight.

Composition of oral rehydration solution The active absorption of glucose in the smooth intestine promotes: Absorption of Na+, which promotes anion (X-) absorption, NaX absorption promotes H2O absorption. Therefore, the composition of oral solution is: Glucose: 110 mM ≈ 2% w/v. Na+: 60 mEq/L. HCO3- & /or citrate to correct blood acidosis.

A typical oral rehydration solution contains: 45 mEq Na+, 20 mEq K+, 35 mEq Cl-, 30 mEq citrate, 25 g of dextrose per liter. These formulations are available il liquid or powder/ packet form for reconstitution.

Oral Colonic Lavage Solution Oral ……………………. solution is used to prepare the bowel for ……………………. examinations (i.e. colonoscopy). The ……………………. is a long narrow flexible tube containing a tiny light & camera at one end. The camera carries pictures of your rectum & colon to a television screen, where they can be viewed by the doctor & nurse.

A Typical formulation of oral colonic lavage solution is: Polyethylene Glycol 3350 236.00 g Sodium sulfate 22.74 g Sodium bicarbonate 6.74 g Sodium Chloride 5.86 g Potassium Chloride 2.97 In 4800 mL disposable container The recommended adult dose of this formulation is: 4 liters of the solution before the GI procedure. The solution must be drunk as 240 mL every 10 minutes until complete consume of the solution.

Syrups

Pharmacists can prepare syrups in their own pharmacy. Syrups are concentrated, aqueous preparations of a sugar or sugar-substitute with or without added flavoring agents & medicinal substances. There are 3 types: ……………………., which is a bout saturated sugar solution without flavour or medicine. ……………………. : is a flavored simple syrup. ……………………. : is a syrup containing medicinal agent. Syrups are useful alternative of solid dosage forms for children & elderly. Pharmacists can prepare syrups in their own pharmacy.

Requirements for preparing syrups: ……………………. of drug solubility & stability; ……………………. must be considered case by case. Medicated syrups are commercially prepared by: ……………………. sucrose & purified water ( simple syrup is obtained); ……………………. & ……………………. the therapeutic agent; ……………………. of flavoring & coloring agents; Addition other necessary & desirable ingredient.

Components of commercial syrups: Sugar (sucrose) or sugar-substitutes used to provide sweetness & viscosity; …………………….; ……………………. agents; ……………………. solvents; Thickeners, or stabilizers.

Advantages of medicated syrups: ……………………. of administration of a liquid form of a bad tasting drug; This ……………………. attractive for youngsters. ……………………., since these dosage forms …………………….; The ……………………. & ……………………. syrups have a soothing effect on the irritated tissue of the throat as they pass over them. In summary: Any ……………………. may be added to flavored syrup. However, care must be played to ……………………. between all components of the syrup. Since there are acidic, basic & neutral flavored syrups, attention must be exercised to the ……………………. of the added drug.

Table 6-6 Table 6-7

Sucrose & Non-Sucrose Based Syrups Characteristics of simple sucrose syrup (85% w/v): …………………….; Preservation (hypertonic solution); High density & specific gravity (s.g. =1.313) Specific gravity = weight of substance weigh of equal volume water 1.313 = w , thus, weight of 100 mL syrup is 131.3 100 131.3g - 85g = 46.3 g or mL of water in the syrup. Thus, 46.3 g of water are mixed with 85 g of sucrose to give syrup 65.5% w/w or 85%w/v.

Thus, the excess of water in 85% w/v syrup is 3.8 mL. Solubility of sucrose in water is 1g /0.5 ml of water, thus, 85 g of sucrose need 42.5 g of water. Thus, the excess of water in 85% w/v syrup is 3.8 mL. These 3.8 mL of water are free of sucrose. This means that syrup is Not saturated but …………………….. If the syrup was completely ……………………., any variation of storage conditions (i.e. cooling) might produce sucrose ……………………. from the syrup. This would start a chain of ……………………. & sucrose …………………….. The syrup would then be very much unsaturated & suitable for microbial growth. Since many official syrups are not saturated suitable ……………………. in the formulation.

Characteristics of MC & HEC: In special circumstances sucrose may be replaced in whole or in part by: I. ……………………. substances (materials converted to glucose in the body) such as: Other sugars (i.e. dextrose); Non-sugars (i.e. sorbitol, glycerin propylene glycol ..etc.). II. ……………………. substances such as methylcellulose (MC) or hydroxyethylcellulose HEC). Characteristics of MC & HEC: ……………………. & absorbed in the blood stream; ……………………. viscosity or vehicle; ……………………. & favors results in facsimile of a true syrups. ……………………. patients & child with carries teeth.

Antihistamine syrup formulation .. etc Page 243

Antimicrobial Preservatives The amount of required preservative for protection depends on: Amount of ……………………. for microbial growth; Nature & inherent preservative activity of some formulative materials (i.e. many flavoring oils); ……………………. of the preservative itself. Some preservatives & correspondent usual concentration: Benzoic acid or Sodium benzoate 0.1 – 0.2% Combinations of m., e., p., b. parbens total 0.1% Alcohol 15 – 20 % Propylene glycol & Glycerin 1 ml / 1ml.

Methods for Preservation of Syrups Storage at ↓ temperature; Addition of preservatives such as glycerin, parabens; alcohol,..etc. Maintenance of a ↑ [] of sucrose as a part of the formulation. Example: Rx Active drug 5 mL volume occupied Other drug solids 3 ml volume occupied Glycerin 15 mL Sucrose 25 g Ethanol 95 % q.s. Purified water q.s. 100 mL How much alcohol would be required to preserve this prescription?

Answer: S. Syrup (85 %w/v) has s.g = 1.313, thus, 85 g sucrose are in 100 ml 131.3 g of solution. 131.3 131.3g – 85g = 46.3 g or 46.3 mL of water. 100mL - 46.3 mL = 53.7 mL is the v. of 85 g of sucrose. Thus, 85 g of sucrose preserves 46.3 mL of water. So, 85 g → 46.3 mL 25 g → X, thus, X = 13.62 mL of water preserved. V. Of sucrose is: 85g → 53.7 mL 25g → x Thus, X = 15.7 mL v. of active drug + v. of other drugs occupies 5 + 3 = 8 mL 1 mL of glycerin preserves 1 mL of water & occupy 1 mL. So, glycerin preserves: 15 mL + 15 mL = 30 mL total. 8. The volume taken care = 13.62 + 15.7 + 8 +30 = 67.3 mL. 9. 100 ml – 67.3 mL of water preserved = 32.68 ml of water which need preservation.

Since it requires about 18% of alcohol to preserve water: So, 18 → 100 mL x → 32.68 mL, → x = 5.88 mL of alcohol 100%. But the available alcohol 95%: So, C1 . V1 = C2 . V2 100 . 5.9 = 95 . V2 → V2 = 6.2 ml of alcohol 95% is required. So, add 6.2 ml of alcohol to the syrup and complete volume up to 100 mL with water.

Flavorants or Flavoring agents ……………………. flavorants as volatile oils (e.g. orange oil, vanilla ..etc.). Flavorants must posses sufficient water solubility. Alcohol may added to improve solubility of flavors.

Colorant Enhance the appeal of syrup. Selection of colorant in correlation with .……………….. (i.e. green with mint, brown with chocolate, etc.). Colorant must be: .………………..; .……………….. with other syrup components; Color stable at the pH range & under the intensity of light that the syrup is likely encountered during its shelf-life.

Preparation of Syrups Preparation of syrup depends on chemical & physical characteristics of the ingredients involved in formulation. There are 4 methods for syrup preparation: Solution of the ingredients .………………..; Solution by agitation .………………..; Addition of sucrose to a medicated liquid or to a flavored liquid; .………………...

Solution with the Aid of Heat Advantages of this method: .……………….. method; The heat provide .………………... Disadvantages of this method: Problems arise when .……………….. ingredients are used; .……………….. of sucrose known as inversion: Sucrose → glucose (dextrose) + fructose (levolose); .……………….. of the sucrose (browning of the syrup);

Preparation procedure: Weigh 85 g of sucrose; Place them in 100 ml of volumetric flask; Add hot water & mix tell complete dissolution of sucrose; Add water up to volume. Dissolve or add as dissolved other components such as flavor, color, medicine, & preservatives; Fill in bottles then, close bottles after cooling.

Solution by Agitation without the Aid of Heat Advantages of this method: It is used for .……………….. ingredients; Avoid sugar .……………….. & .………………... Disadvantages of this method: .……………….. & .……………….. are employed for large scale preparation; Needs .……………….. of preparation; .……………….. to preservation.

Preparation Procedure: Put sugar & other formulative agents in large vessel to permit thorough agitation; Mix well tell complete dissolution of sugar & other soluble ingredients; Drugs are .……………….. .……………….. & then, added to syrup; Add water up to volume; .……………….. directly to syrup because it needs long time to be dissolved.

Addition of sucrose to Medicated liquid or to a Flavored Liquid It is frequently used when .……………….. or .……………….. are employed as the source of medications. These fluid extracts are .………or ……….. preparations. If the alcohol soluble components are .……………….., means of ↑ their .……………….. are employed. If the .……………….. components are .……………….. components, they are generally removed by: Mixing the tincture or fluid extract with .………………..; Leave the mixture to stand tell .……………….. of water insoluble compounds; .………………... Add sucrose to the filtrate & complete the procedure. If fluid extracts (drug/s) are .……………….. add them directly to a .……………….. to medicate it.

Percolation

Types of percolation: Percolation of .……………….. to prepare syrup or; Percolation of .……………….. components: Preparation of extract; Add syrup to the .……………….. to achieve the desired syrup. Preparation of Ipecac Syrup: Prepare the extract by .………………..; Add .……………….. & .……………….. to the percolated ipecac. The drug ipecac consists of the dried rhizome & roots of Cephaelis ipecacuanha. The extracted alkaloids by .……………….. with .……………….. solvent are: emetine, cephaeline, & psychotrine.

It is an emetic syrup. Usual dose is 15 ml for .……………….. in children when stomach evacuation is desired. Vomiting is achieved within ½ hour in 80% of treated children. Abuse of this syrup was in young women in attempt to .………………... Excess of emetine in tissue due to excess use cause cardiac muscle damage. Toxic symptoms are: .………………..; .……………….. symptoms; .………………...

Elixirs

Lower dissolving capacity Higher dissolving capacity Elixirs are, sweetened, flavored, hydro-alcoholic solutions intended for oral use. Types of elixirs: Non-medicated elixir → employed as vehicle. Medicated elixir → employed for therapeutic effect of the drug they contain. Syrup Elixir .……………….. Less sweet .……………….. Less viscose .……………….. Lower sucrose content Lower dissolving capacity Higher dissolving capacity .……………….. Simple manufacturing .……………….. More stable

Elixir with 10 – 12 % alcohol don’t need preservatives. The amount of alcohol in elixir depends on solubility of dissolved agents. Elixir with 10 – 12 % alcohol don’t need preservatives. This alcoholic content represents Disadvantage for: .……………….. patients; Adults who .……………….. consumption; Also represents another disadvantage for many .………………... Because of their .……………….. & .……………….. oils content, elixirs must be stored in: Tightly .……………….. containers; .……………….. containers; In .……………….. place.

Preparation of Elixirs By simple solution (.………………..); By mixture of 2 liquid ingredients: Dissolve alcohol soluble ingredients; Dissolve water soluble ingredients separately; Add .……………….. solution to the .……………….. one ( don’t make the reverse). Add the desired .……………….. up to volume. Frequently the final mixture is not clear. What is the reason behind this? What can you do, if the obtained solution is cloudy?

Contribution .……………….. of the Hydro-alcoholic solvent; What is the role of Glycerin; Syrup; Sorbitol & Propylene glycol in in Elixir Formulation? Contribution .……………….. of the Hydro-alcoholic solvent; Assist the .……………….. of the solute; .……………….. of the preparation .……………….. of the formulation.

Non-Medicated elixirs in extemporaneous preparations: Addition of a drug .……………….. vehicle; Dilution of an .………………..( amount of alcohol must be equal in the two elixirs). The selection of a vehicle depends on: .……………….. & .……………….. of the drug in both .……………….. & .………………... The amount of alcohol must be only slightly above the amount which is required to: .……………….. .……………….. of the drug. Flavors, Colors and all components must be compatible.

Medicated Elixirs Usually most elixirs contains only .……………….. single therapeutic agent. Physician prefer this kind of elixir. What is the advantage of having a single drug in the elixir?

Phenobarbital elixirs Page 247 Digoxin elixir & figures. Page 251