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Pharmaceutical solutions
for oral administration
By :Dr. Nehal Aly Afifi
Professor of Pharmacology
Cairo university
Liquid dosage forms
One of the oldest dosage forms used in treatment.
Rapid & High absorption of soluble medicinal product...
Solutions: Definition
Pharmaceutical solutions are extensively used as dosage forms for
the oral administration of therape...
Prof.Dr/ Nehal Afifi
4
• Pharmaceutical solutions contain a range of excipients, each
with a defined pharmaceutical purpos...
Advantages of pharmaceutical solutions
1. The drug immediately available for absorption.
By providing drug in a solution, ...
Disadvantages of solutions
1. Drug stability is reduced in Sol by hydrolysis or oxidation.
For this reason, Sol. is common...
Advantages & disadvantages of pharmaceutical
solutions for oral administration
Advantages Disadvantages
• 1. Drug availabl...
Formulation of Pharmaceutical sol.
Drug(s) + Range of excipients include:
The vehicle ( Solvent):
 - Purified Water.
 - ...
Drug Solubility
• In pharmaceutical sols both therapeutic drugs and the
excipients are required to be present in sol over ...
Factors Affecting Solubility
• 1- physicochemical properties of Therapeutic agent :
• The solubility of drug molecules in ...
Prof.Dr/ Nehal Afifi
11
• 2- Temperature:
• Most compounds are more soluble in higher temperature.
• 3- pH
• The vast majo...
Methods to enhance/optimize the solubility
1. Appropriate selection of drug salt:
• The majority of therapeutic agents are...
Prof.Dr/ Nehal Afifi
13
3. Use of co-solvents :
Co-solvents are liquid components incorporated into a
formulation to enhan...
Excipients used in pharmaceutical solutions
for oral administration
• Excipients are pharmacologlly inert compounds that a...
Vehicles (Solvents) for Liquid Dosage Forms
A vehicle is the medium containing the ingredients of a drug.
In solutions, th...
Types of water
1. Potable water : drinking water, should be palatable &
safe for drinking, Its chemical composition may in...
Water as a vehicle
3. Water for preparations : potable or freshly boiled and cooled
water, used in oral or external LDF no...
Prof.Dr/ Nehal Afifi
18
• II. Co-solvents
• Employed to increase the solubility of therapeutic agent
within the formulatio...
Prof.Dr/ Nehal Afifi
19
• Propylene Glycol USP
• Propylene Glycol is an odourless, colourless, viscous liquid
that contain...
Surface-active agents
• As the conc. increased, the interface will become saturated with
surface-active agent & the molecu...
B. Complexation
• Complexation refers to the interaction of a poorly
soluble therapeutic agent with an organic molecule,
e...
IV. Common Excipients in Pharmaceutical Sol.
• Excipients that are commonly employed in formulation of
pharmaceutical solu...
Prof.Dr/ Nehal Afifi
23
• The conc. of buffer salts employed in the oral solutions
should be selected to offer sufficient ...
Sweetening Agents
• Sweetening agents are employed in liquid formulations
designed for oral administration specifically to...
Viscosity -enhancing Agents
• The administration of oral solutions to patients by using a
syringe, a small-metered cup or ...
Antioxidants
• Antioxidants included in pharm. Sol. to enhance the stability of
drugs that susceptible to chemical degrada...
Preservatives
• Preservatives are included in pharmaceutical solutions to
reduce or prevent the microbial growth of the fo...
Flavours and colourants
• The vast majority of drugs in solution are unpalatable,→ so
the addition of flavors to mask the ...
Flavour Adjuncts
• Certain excipients added to oral solution formulations, referred
to as flavour adjuncts (e.g. menthol, ...
Types of pharmaceutical solutions
• Pharmaceutical sols for oral administration:
• 3 principal types of sol. formulations ...
Oral solutions
• Oral solutions are administered to the GIT to provide systemic
absorption of the therapeutic agent.
• Ora...
Oral syrups
• Syrups are highly concentrated, aqueous sols of sugar or a
sugar substitute that contain a flavouring agent,...
Prof.Dr/ Nehal Afifi
33
• The major components of syrups are as follows:
• ■ Purified water
• ■ Sugar (sucrose) or sugar s...
Medicated Sugar-free Syrup
• All Medicinal products designed for
administration to children & diabetic
patients must be su...
Preservatives
• Preservatives are not required in traditional syrups containing
high conc. of sucrose.
• Addition of prese...
Flavours
• Flavours employed to the unpalatable taste of a therapeutic agent
even in presence of the sweetening agents.
• ...
Oral elixirs
• Elixir is a clear, hydroalcoholic sol. formulated for oral use.
• The presence of alcohol in elixirs cause ...
Prof.Dr/ Nehal Afifi
38
• 1. Phenobarbital Elixir:
• Phenobarbital (therapeutic agent) 0.4% w/v
• Orange oil (flavour) 0.0...
Linctuses
• A liquid oral preparation used for a demulcent,
expectorant or sedative effect in treatment of cough.
• Linctu...
Mouthwashes /gargles
• Mouth washes/gargles are designed for the treatment of
infections and inflammation of the oral cavi...
Solutions for oral dosage
• Containers for dispensed oral solutions:
• Plain, amber medicine bottles should be used, with ...
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Pharmaceutical Solutions for Oral administration

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Pharmaceutical Solutions for Oral administration

  1. 1. Pharmaceutical solutions for oral administration By :Dr. Nehal Aly Afifi Professor of Pharmacology Cairo university
  2. 2. Liquid dosage forms One of the oldest dosage forms used in treatment. Rapid & High absorption of soluble medicinal products . Particular use for individuals having difficulty in swallowing SDF (e.g.: Pediatric, Geriatric, Intensive care & Psychiatric) Patients. Solutions are homogeneous liquid preparation containing one or more completely dissolved components (One-phase system). Active ingredients dissolved within vehicles to obtain uniform sols. In general, water used as vehicle in w medicaments dissolved, water is Non-toxic, Nonirritant, Tasteless, Relatively cheap, and many drugs are water soluble (Aqueous sol.) Some drugs not water soluble so mixed with other solvents NonAqueous 2 Prof.Dr/ Nehal Afifi
  3. 3. Solutions: Definition Pharmaceutical solutions are extensively used as dosage forms for the oral administration of therapeutic agents. Pharmaceutical solutions defined as liquid preparations in which the therapeutic agent and the various excipients are dissolved in the chosen solvent system. Pharmaceutical solutions are homogeneous, i.e. the therapeutic agent(s) and excipients are dissolved in the vehicle. Pharmaceutical solutions for oral administration are in non-sterile dosage forms. Pharmaceutical sol. classified according to their intended use as Oral solution, - Otic solution Ophthalmic solution, - Topical solution. Parenteral preparations Sol. categorized by a traditional name related to the solvent system used and/or their intended function (e.g. Spirits, Syrups Tinctures, Aromatic waters, and Elixirs). 3 Prof.Dr/ Nehal Afifi
  4. 4. Prof.Dr/ Nehal Afifi 4 • Pharmaceutical solutions contain a range of excipients, each with a defined pharmaceutical purpose. Examples include: • The vehicle, usually purified water • Co-solvents, e.g. propylene glycol, glycerin, alcohol • Surface-active agents specifically to enhance solubility of the therapeutic agent in the vehicle. • Preservatives, e.g. parahydroxybenzoate esters (methylhydroxybenzoate and propylhydroxybenzoate), boric acid and borate salts, sorbic acid and sorbate salts. • Sweeteners, e.g. glucose, saccharin, aspartame • Rheology (viscosity) modifiers, e.g. hydrophilic polymers • (cellulose derivatives, alginic acid, polyvinylpyrrolidone) • Antioxidants, e.g. sodium formaldehyde sulphoxylate, • butylated hydroxyanisole, butylated hydroxytoluene • Buffers to regulate the pH of the formulation, e.g. citrate buffer.
  5. 5. Advantages of pharmaceutical solutions 1. The drug immediately available for absorption. By providing drug in a solution, the dissolution phase absorption can bypassed → quicker absorption. 2. Flexible dosing is possible. The active ingredient within sol. present in a certain Conc. per unit volume. 3. Solutions are designed for any route of absorption: the oral route of administration , via Parenteral preparations (injections), enemas for rectal use, Topical (for use on skin) & ophthalmic preparations are all sols. 4. No need to shake the container. Unlike suspensions as the active ingredient is dissolved within the vehicle. 5. Facilitate swallowing in difficult cases (e.g. infants or the elderly). It is more easier for patients to take solution 5 Prof.Dr/ Nehal Afifi
  6. 6. Disadvantages of solutions 1. Drug stability is reduced in Sol by hydrolysis or oxidation. For this reason, Sol. is commonly has a shorter expiry date than equivalent solid dosage forms. 2. It is difficult to mask unpleasant tastes. 3. A major disadvantage ; they are much larger & more bulky, difficult to transport. Liquids packed in glass bottles are obviously prone to breakage and cause loss of the preparation. 4. Technical accuracy is needed to measure the dose on admin. patient accuracy in measuring a dose is required 5. Some drugs are poorly soluble so it is necessary to alter vehicle or drug form in order to formulate a convenient prep. 6. A measuring device is needed for admin. so need to be supplied to the patient to be able to measure an accurate dose 6 Prof.Dr/ Nehal Afifi
  7. 7. Advantages & disadvantages of pharmaceutical solutions for oral administration Advantages Disadvantages • 1. Drug available immediately for absorption→ bioavailability of sols is greater than that of oral solid-dosage forms. • 2. Flexible dosing. • 3. designed for any route of administration. • 4. Not need to shake container. • 5. Facilitates swallowing in difficult cases. 1.Drug stability reduced in sol. • 2. Difficult to mask unpleasant tastes. • 3. Bulky, difficult to transport & prone to container breakages. • 4. Technical accuracy needed • to measure dose on administ. • 5. Measuring device needed for administration. • 6. Some drugs poorly soluble 7 Prof.Dr/ Nehal Afifi
  8. 8. Formulation of Pharmaceutical sol. Drug(s) + Range of excipients include: The vehicle ( Solvent):  - Purified Water.  - Oil • Co-solvents, e.g. propylene glycol , glycerol, ethanol surface-active agents  - To enhance solubility of the therapeutic sub. in vehicle. Preservatives,  - Against microbial contamination Sweetening agents, e.g. glucose, saccharin, aspartame Viscosity modifiers, e.g. cellulose derivatives, Antioxidants, e.g. butylated hydroxytoluene Coloring & Flavoring agents (oral only) Buffering agents , to regulate the pH of the formulation, 8 Prof.Dr/ Nehal Afifi
  9. 9. Drug Solubility • In pharmaceutical sols both therapeutic drugs and the excipients are required to be present in sol over the shelf-life. • As a result solutions are termed homogeneous. • 1.IF the aqueous solubility of drug is high at the selected pH of formulation, → therapeutic drug is readily incorporated into vehicle and formulated as oral sol. • 2.IF aqueous solubility of drug is moderate at selected pH , i.e. aqueous solubility is less than requested conc. of drug→ the solubility of drug in sol. must be enhanced using co-solvents. • 3.IF aqueous solubility of drug is low at selected pH of formulation. The difference between aqueous solubility of drug and the required conc. is too great to the use of cosolvents or surfactants in the solubilised form & toxic when administered orally. The drug therefore formulated as a suspension 9 Prof.Dr/ Nehal Afifi
  10. 10. Factors Affecting Solubility • 1- physicochemical properties of Therapeutic agent : • The solubility of drug molecules in a solvent are dependent on several physicochemical properties, including molecular weight, volume, density, and number of hydrogen bonds. • Particle size: • Reduction of particle size increase the rate of solubility. • The solubility of a chemically related series of drugs is inversely related to their melting points; so as the melting point of drug increased, the solubility decrease. • The solubility of a drug is directly affected by the type of chemical substituent groups. • The solubility of drugs containing hydrophilic groups (e.g. OH, COO, ammonium ion) will accordingly be greater than those containing lipophilic substituent groups, e.g. Prof.Dr/ Nehal Afifi 10
  11. 11. Prof.Dr/ Nehal Afifi 11 • 2- Temperature: • Most compounds are more soluble in higher temperature. • 3- pH • The vast majority of drug subs. are either acids or bases . • The solubility of therapeutic agents are pH-dependent. • The solubility of acids & bases increases as the degree of ionization increases. • The solubility of acidic compounds increases as the pH of the sol. is increased (above the pKa) & solubility of basic comps increase as the pH is lowered below the pKa 4. Polarity: Polar comp. more soluble in Polar solvents as water & ethanol . Non polar comps more soluble in non polar solvents as chloroform Conc. acid or alkali added to form water- soluble salts. Conversilly,The organic bases more soluble in organic solvents than the corresponding salt forms.
  12. 12. Methods to enhance/optimize the solubility 1. Appropriate selection of drug salt: • The majority of therapeutic agents are available in a salt form, each form a different aqueous solubility. • Select the drug salt provide the required solubility in the dosage form. • 2. Optimization of the pH of the formulation: • The solubility of ionized therapeutic agent is a function of both the pKa and the pH of the formulation. • The acceptable pH range for oral sols is large, ranging from 5 to 8 pH units. • The selection of a pH value for formulation to optimize the ionization and solubility of the therapeutic agent is important. • The Control of pH in formulation is achieved by using a buffer Prof.Dr/ Nehal Afifi 12
  13. 13. Prof.Dr/ Nehal Afifi 13 3. Use of co-solvents : Co-solvents are liquid components incorporated into a formulation to enhance the solubility of poorly soluble drugs. The Commonly employed co solvents include , glycerol, propylene glycol, ethanol and polyethylene glycol. The final choice of the co-solvent system for a particular formulation involves consideration of the solubility of the therapeutic agent in the vehicle, the toxicity of the vehicle and the cost of formulation. The range of concentrations of each co-solvent used in oral formulations is primarily limited by concerns regarding toxicity.
  14. 14. Excipients used in pharmaceutical solutions for oral administration • Excipients are pharmacologlly inert compounds that are included in the pharmaceutical formulations. • To facilitate the administration of the dosage form, e.g. pourability, and palatability, • To protect the formulation from issues regarding physical and chemical stability. • To enhance the solubility of the therapeutic agent. • Pharmaceutical sols contain a wide range of excipients. • l- The vehicle: • The preferred & most commonly used vehicle in sols for oral administration is Purified Water USP, due to the low cost and low toxicity . Prof.Dr/ Nehal Afifi 14
  15. 15. Vehicles (Solvents) for Liquid Dosage Forms A vehicle is the medium containing the ingredients of a drug. In solutions, the vehicle is the solvent. The choice of a vehicle depends on:  The intended use of the preparation The nature & physicochemical properties of active ingredients. Water as a vehicle Water used as the primary solvent; widely available, relatively inexpensive, palatable and non-toxic for oral use, non-irritant for external use. Water is also a good solvent for many ionizable drugs. Salts of organic compounds are more soluble in water water is the preferred solvent. for solutions to be taken orally, used ophthalmic ally, or injected. 15 Prof.Dr/ Nehal Afifi
  16. 16. Types of water 1. Potable water : drinking water, should be palatable & safe for drinking, Its chemical composition may include mineral impurities which could react with drugs, e.g. the presence of calcium carbonate in hard water. 2. Purified water USP, obtained from potable water by distillation, ion exchange treatment,or reverse osmosis. Distilled water is purified water prepared by distillation. Compared with ordinary drinking water: Purified Water, more free of solid impurities. When evaporated to dryness, not yield greater than 0.001% of residue (1 mg of total solids /100 mL of sample evaporated). Purified Water is intended for use in preparation of aqueous DF, except those intended for Parenteral administration (injections). 16 Prof.Dr/ Nehal Afifi
  17. 17. Water as a vehicle 3. Water for preparations : potable or freshly boiled and cooled water, used in oral or external LDF not intended to be sterile. 4. Water for injections: is pyrogen-free distilled water, sterilized immediately after collection and used for Parenteral preparations. 5. Chloroform water : used as antimicrobial preservative and also adds sweetness to preparations. chloroform available as: Chloroform BP = 100% v/v 6. Aromatic water : saturated solution of volatile oils in water and are used to provide a pleasant flavor or aroma, e.g. Peppermint Water, USP. Used as a vehicle in oral sol. Some have mild carminative action For example diluted Aromatic waters are usually prepared from a conc. ethanolic sol. in a dilution of 1 part to 39 parts with water. 17 Prof.Dr/ Nehal Afifi
  18. 18. Prof.Dr/ Nehal Afifi 18 • II. Co-solvents • Employed to increase the solubility of therapeutic agent within the formulation. • Co-solvents used in the formulation of oral solutions are : • Glycerol (also termed glycerin) • Glycerol is a clear odorless, viscous liquid, with a sweet taste , and miscible with both water and alcohol. • Its co-solvency properties due to the presence of three hydroxyl gps;oH. It has similar co-solvency properties to ethanol • Alcohol USP (CH3CH2OH) • Contain between 94.9 and 96.0% v/v ethyl alcohol(ethanol). • Commonly used as a co-solvent, both as a single and with other co-solvents, e.g. glycerol. • The known pharmacological & toxicological effects of alcohol have compromised its use in pharmaceutical preparations.
  19. 19. Prof.Dr/ Nehal Afifi 19 • Propylene Glycol USP • Propylene Glycol is an odourless, colourless, viscous liquid that contains two hydroxyl groups; oH . • Used in pharmaceutical preparations as a co-solvent, generally as a replacement for glycerin. • III. Miscellaneous agents used to enhance solubility of • therapeutic agents. • These include the use of surface-active agents & Complexation. • A. Surface-active agents • These are chemicals that possess both hydrophilic (water-liking) and hydrophobic (water-disliking) regions. • At dilute conc. surface-active agents will orient at the interface between two phases (e.g. water/oil), with the hydrophilic and hydrophobic regions of the molecule being positioned to the hydrophilic and hydrophobic phases, respectively.
  20. 20. Surface-active agents • As the conc. increased, the interface will become saturated with surface-active agent & the molecules that are present in the bulk aqueous phase will orient themselves to shield the hydrophobic regions of surface-active agent. • This orientation is referred to as a micelle ‫.المذيلة‬ • The conc. of surface-active agent at this occurs is termed the critical micelle concentration (CMC). • In this the core of the micelle represents a hydrophobic region into which the poorly water-soluble drugs partition. • For example, if the therapeutic agent is poorly soluble, the molecule will locate exclusively within the micelle. • if the drug is water-insoluble but contains polar groups, the molecule will orient within the micelle, w & drug solubilised within the colloidal micelles; due to their small size →the resulting sol. appears homogeneous to the naked eye. Prof.Dr/ Nehal Afifi 20
  21. 21. B. Complexation • Complexation refers to the interaction of a poorly soluble therapeutic agent with an organic molecule, e.g. surface-active agents, hydrophilic polymers to generate a soluble intermolecular complex. • One particular concern regarding the use of solution of drug complexes is the ability of the complex to dissociate following administration. • This is particularly important in situations where the complexing agent is a hydrophilic polymer, as the high molecular weight of the drug–polymer complex would prevent drug absorption across biological membranes. Prof.Dr/ Nehal Afifi 21
  22. 22. IV. Common Excipients in Pharmaceutical Sol. • Excipients that are commonly employed in formulation of pharmaceutical solutions are: (1) buffers; (2) sweetening agents; & (3) viscosity-enhancing agents. • (1) Buffers: • Buffers employed within pharmaceutical sols to control pH of the formulated product and, to optimize the physicochemical performance of the product. • Typically pH control is performed: To maintain the solubility of therapeutic agent in formulated prod • The solubility of drugs is pH-dependent , therefore, solubility of therapeutic agent compromised by small changes in pH To enhance the stability of the products in which the chemical stability of the active agent is pH-dependent. Prof.Dr/ Nehal Afifi 22
  23. 23. Prof.Dr/ Nehal Afifi 23 • The conc. of buffer salts employed in the oral solutions should be selected to offer sufficient control of the pH of the formulation but yet should be overcome by biological fluids following administration. • Examples of buffer salts used in pharmaceutical solutions include: • ■ Acetates (acetic acid and sodium acetate): about 1–2% • ■ Citrates (citric acid and sodium citrate): about 1–5% • ■ Phosphates (sodium phosphate and disodium phosphate): about 0.8–2%. • the buffer system used in solution formulations should not adversely affect the solubility of the therapeutic agent, e.g. the solubility of drugs may be affected in the presence of phosphate salts.
  24. 24. Sweetening Agents • Sweetening agents are employed in liquid formulations designed for oral administration specifically to increase the palatability of the therapeutic agent. • The main sweetening agents employed in oral preparations are sucrose, liquid glucose, glycerol, sorbitol, saccharin sodium and aspartame. • The use of artificial sweetening agents in formulations is increasing and, in many formulations, saccharin sodium is used either as the sole sweetening agent or in • combination with sugars or sorbitol to reduce the sugar • concentration in the formulation. • The use of sugars in oral formulations for children and patients with diabetes mellitus is to be avoided. Prof.Dr/ Nehal Afifi 24
  25. 25. Viscosity -enhancing Agents • The administration of oral solutions to patients by using a syringe, a small-metered cup or a traditional 5-ml spoon. • The viscosity of formulation must be controlled to ensure the accurate measurement of the dispensed volume. • increasing the viscosity of → increase the palatability. • Certain liquid formulations do not require the addition of VEA, e.g. syrups, due to their inherent viscosity. • The viscosity of pharmaceutical solutions increased by the addition of non-ionic or ionic hydrophilic polymers. 1. Non-ionic (neutral) polymers: – cellulose derivatives e.g.: ● methylcellulose ●hydroxyethylcellulose • ● hydroxypropylcellulose • –– Polyvinylpyrrolidone 2. Ionic polymers: – sodium carboxymethylcellulose (anionic) • – sodium alginate (anionic). Prof.Dr/ Nehal Afifi 25
  26. 26. Antioxidants • Antioxidants included in pharm. Sol. to enhance the stability of drugs that susceptible to chemical degradation by oxidation. • Antioxidants are compounds that inhibit free radical-induced drug decomposition. • Both water-soluble & water-insoluble antioxidants are available. • Antioxidants for aqueous formulationse eg; Sodium sulphite, sod. metabisulphite, sod. formaldehyde sulphoxylate and ascorbic acid. • Antioxidants used in oil-based solutions e.g; butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) and propyl gallate. • Antioxidants employed in low concentrations ( ˂ 0.2% w/w) . • Antioxidants employed in conjunction with chelating agents, e.g. ethylenediamine tetraacetic acid, that act to form complexes with heavy-metal ions. Prof.Dr/ Nehal Afifi 26
  27. 27. Preservatives • Preservatives are included in pharmaceutical solutions to reduce or prevent the microbial growth of the formulation. • Ideally, preservatives should exhibit the following properties: • 1. possess a broad spectrum of antimicrobial activity includes Gram-positive,Gram-negative bacteria & fungi. • 2.be chemically and physically stable over the shelf-life of the product. 3. have low toxicity. • Preservatives for use in oral pharmaceutical solutions : • ■ benzoic acid and salts (0.1–0.3%). • ■ sorbic acid and its salts (0.05–0.2%). • ■ Alkyl esters of parahydroxybenzoic acid (0.001-0.2%). • A combination of two preservatives employed in solutions to enhance the antimicrobial spectrum. • Methyl & propyl parahydroxybenzoates (in a ratio 9:1). 27 Prof.Dr/ Nehal Afifi
  28. 28. Flavours and colourants • The vast majority of drugs in solution are unpalatable,→ so the addition of flavors to mask the taste of drug subs. • Flavours added to make a medicine more acceptable to take. • Four basic taste sensations are salty, sweet, bitter & sour • – Flavours used to mask a salty taste include: ● butterscotch ● apricot ● peach ● vanilla● wintergreen mint. • – Flavours used to mask a bitter taste include: ● cherry. ● mint. ● anise. • – Flavours used to mask a sweet taste include: ● vanilla. ● fruit and berry. • – Flavours used to mask a sour taste include: ● citrus flavours. ● raspberry. • A combination of flavours is used to achieve the optimal taste-masking property. 28 Prof.Dr/ Nehal Afifi
  29. 29. Flavour Adjuncts • Certain excipients added to oral solution formulations, referred to as flavour adjuncts (e.g. menthol, chloroform). • flavour adjuncts add flavor to formulation and in addition, act to desensitise the taste receptors. • These agents augment the taste-masking properties . • Colourants: • Colours are pharmaceutical ingredients that impart the preferred colour to the formulation. • When used in combination with flavours, the selected colour should ‘match’ the flavour of the formulation, • e.g. green with mint-flavoured solutions, • red for strawberry-flavoured formulations. • Although colours is not a prerequisite for all pharmaceutical sol., certain categories of solution (e.g. mouthwashes/gargles) are normally coloured. Prof.Dr/ Nehal Afifi 29
  30. 30. Types of pharmaceutical solutions • Pharmaceutical sols for oral administration: • 3 principal types of sol. formulations administered orally: oral solutions, oral syrups and oral elixirs. • Other sol. formulations employed for a local effect, e.g. • mouthwashes/gargles . 30 Prof.Dr/ Nehal Afifi
  31. 31. Oral solutions • Oral solutions are administered to the GIT to provide systemic absorption of the therapeutic agent. • Oral solutions formulated over a broad pH range due to the flexibility of GI environment. • The usual pH of oral solutions is about 7.0, unless there are issues regarding the solubility or stability of drug. • Typically the following excipients used in the formulation:. • ■ Buffers (e.g. citrate, phosphate) • ■ Preservatives (e.g. parabens, benzoic acid, sorbic acid). • ■ Antioxidants (water-soluble antioxidants used, e.g. sodium metabisulphite 0.01–1.0% w/w) • ■ Flavours and colours. • ■ Viscosity-modifying agents (to affect the pourability of the Formulation, hydrophilic polymers are used, e.g. sodium alginate, hydroxyethylcellulose). Prof.Dr/ Nehal Afifi 31
  32. 32. Oral syrups • Syrups are highly concentrated, aqueous sols of sugar or a sugar substitute that contain a flavouring agent, e.g. • cherry syrup, orange syrup, raspberry syrup. • Unflavored (Traditional syrup) composed of aqueous sol. containing 85% sucrose. • It is important to ensure that: • 1.The drug substance soluble within the syrup base. • 2. The syrup vehicle is appropriate to physicochemical properties of drug subs. For example, cherry syrup & orange syrup are acidic, therefore solubility of acidic drugs lowered & resulting in precipitation of drug subs. • The use of acidic syrups additionally result in reduced chemical stability for acid-labile therapeutic agents. Prof.Dr/ Nehal Afifi 32
  33. 33. Prof.Dr/ Nehal Afifi 33 • The major components of syrups are as follows: • ■ Purified water • ■ Sugar (sucrose) or sugar substitutes(Artificial sweeteners. • ■ Preservatives. ■ Flavours. ■ Colours. • Traditionally syrups composed of sucrose (60 and 80%) and purified water. [Not need the addition of other sweetening agents ,viscosity-modifying agents , or preservatives]. • Sorbitol is a non-sucrose bases replace traditional syrup In some formulations. • Sorbitol Sol. USP contains 64% w/w sorbitol (a polyhydric alcohol) • Other alternatives based on mixtures of sorbitol & glycerin available • Non-sucrose bases mixed with traditional syrups, if the oral syrups possess a low conc. of sucrose. • More recently, many products formulated as medicated sugar-free syrups due to the glycogenetic & cariogenic properties of sucrose.
  34. 34. Medicated Sugar-free Syrup • All Medicinal products designed for administration to children & diabetic patients must be sugar-free. • Syrup Substitutes must provide an equivalent sweetness, viscosity and preservation to the original syrup. • Artificial sweeteners: • Artificial sweeteners include Saccharin sodium, and Aspartame. • Non-glycogenetic viscosity modifiers (e.g.methylcellulose, and hydroxy ethyl cellulose) . • Preservatives(e.g. sodium benzoate, benzoic acid &parahydroxy benzoate ester ) are included in medicated sugar-free syrup. Prof.Dr/ Nehal Afifi 34 therapeutic agent Saccharine Sod. purified water Preservative flavoring agents
  35. 35. Preservatives • Preservatives are not required in traditional syrups containing high conc. of sucrose. • Addition of preservatives is required in: 1. sugar-free syrups, 2. syrups in which sucrose substituted by polyhydric alcohol. 3. traditional syrups contain lower conc. of sucrose, • Examples of commonly used preservatives include: • Mixtures of parahydroxybenzoate esters (methylhydroxy benzoate and propylhydroxybenzoate in a ratio of 9:1). • The typical concentration range is 0.1–0.2% w/v. • The preservative efficacy decreased in the presence of hydrophilic polymers (generally employed to enhance • viscosity), due to interaction of preservative with polymer. • Other preservatives include benzoic acid (0.1–0.2%) or sodium benzoate (0.1–0.2%). Prof.Dr/ Nehal Afifi 35
  36. 36. Flavours • Flavours employed to the unpalatable taste of a therapeutic agent even in presence of the sweetening agents. • The conc. of flavour in oral syrups is that which required to provide the required degree of taste-masking effectively. • 1.The flavours of natural origin (e.g. peppermint, lemon, herbs ) and available as oils, extracts, spirits or aqueous sol. • 2. synthetic flavours: • Certain flavors also associated with a (mild) therapeutic activity, e.g; antacids contain mint due to the carminative effect. • flavours offer a taste-masking effect by eliciting a mild local anesthetic effect on the taste receptors,e.g;peppermint oil, chloroform, menthol. • ■ Colours :natural or synthetic water soluble, photo-stable ingredients that selected according to flavour of preparation. • E.g;, mint-flavoured formulations with a green colour, banana- flavoured sol. with a yellow colour . Must not chemically or physically interact with the other components of the formulation. Prof.Dr/ Nehal Afifi 36
  37. 37. Oral elixirs • Elixir is a clear, hydroalcoholic sol. formulated for oral use. • The presence of alcohol in elixirs cause a problem in paediatric formulations and, for adults who wish to avoid alcohol. • The typical components of an elixir are as follows: • ■ Purified water. • ■ Alcohol: employed as a co-solvent to ensure solubility of all ingredients. the conc. Of alcohol varies depending on formulation. • Generally, Alcohol conc. is greater than 10% v/v; however, in some preparations, alcohol conc. greater than 40% v/v. • ■ Polyol co-solvents. e.g. propylene glycol, glycerol, employed in elixirs to enhance the solubility of drug subs. & excipients. • The inclusion of co-solvents enable the alcohol conc. to be reduced. The conc. of co-solvents is dependent on conc. of alcohol present;e.g; in USP: Phenobarbital Elixir & Theophylline Elixir Prof.Dr/ Nehal Afifi 37
  38. 38. Prof.Dr/ Nehal Afifi 38 • 1. Phenobarbital Elixir: • Phenobarbital (therapeutic agent) 0.4% w/v • Orange oil (flavour) 0.025% v/v • Propylene glycol (co-solvent) 10% v/v • Alcohol 20% v/v • Sorbitol solution (sweetener) 60% v/v • Colour As required • Purified water ad 100% • 2. Theophylline Elixir • Theophylline (therapeutic agent) 0.53% w/v • Citric acid (pH regulation) 1.0% w/v • Liquid glucose (sweetening agent) 4.4% w/v • Syrup (sweetening agent) 13.2% v/v • Saccharin sodium (sweetening agent) 0.5% w/v • Glycerin (co-solvent) 5.0% v/v • Sorbitol solution (co-solvent) 32.4% v/v • Alcohol 20% v/v • Lemon oil (flavour) 0.01% w/v
  39. 39. Linctuses • A liquid oral preparation used for a demulcent, expectorant or sedative effect in treatment of cough. • Linctuses are viscous preparations that contain the therapeutic agent dissolved in a vehicle composed of a high percentage of sucrose and, if required, other sweetening agents. • These formulations are administered orally. • Primarily employed for treatment of cough, due to their soothing actions on the inflamed mucous membranes. • Linctuses also be formulated as sugar-free alternatives in which sucrose is replaced by sorbitol and the required Conc. of sweetening agent. Prof.Dr/ Nehal Afifi 39
  40. 40. Mouthwashes /gargles • Mouth washes/gargles are designed for the treatment of infections and inflammation of the oral cavity. • Formulations designed for this purpose employ water as the vehicle, although a co-solvent, e.g. alcohol, may be employed to solubilise the active agent. • The use of alcohol as a co-solvent act to enhance the antimicrobial properties of the therapeutic agent. • Other formulation components are frequently required to enhance the palatability and acceptability of preparation. • These include preservatives, colours, flavouring agents and non-cariogenic sweetening agents. • Oral drops: oral solutions or suspensions administered in small volumes, using a suitable measuring device. • E.g.; Abidec® vitamin drops. Prof.Dr/ Nehal Afifi 40
  41. 41. Solutions for oral dosage • Containers for dispensed oral solutions: • Plain, amber medicine bottles should be used, with a re-closable child-resistant closure. • A 5 mL measuring spoon or an appropriate oral syringe should be supplied to the patient. • Advice to store away from children should then be given. Special labels and advice for dispensed oral solutions: • An expiry date should appear on the label for the final prepared sols. Most 'official' mixtures & some oral sols are freshly prepared. • 'Official' elixirs, linctuses and manufactured products are generally more stable, unless diluted. • Diluted products generally have a shorter shelf life than undiluted preparation. • Linctuses should sipped & swallowed slowly without addition of water 41 Prof.Dr/ Nehal Afifi

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