Pharmaceutics I Lecture 1: Pharmaceutical Solutions PDF

Alexandria university Faculty of Pharmacy Department of Pharmaceutics PharmD Program Semester Three Pharmaceutics I (02-06-01202) PHARMACEUTICS I Lecture 1: PHARMACEUTICAL SOLUTIONS Dr. Shaimaa Osama, PhD...

Alexandria university Faculty of Pharmacy Department of Pharmaceutics PharmD Program Semester Three Pharmaceutics I (02-06-01202) PHARMACEUTICS I Lecture 1: PHARMACEUTICAL SOLUTIONS Dr. Shaimaa Osama, PhD 1  Solutions Colloids Topics Suspensions (Course Content) Emulsions Pharmaceutical Calculations 2 LECTURE OUTLINE After completion of this lecture, you will be able to: Define and list the advantages and disadvantages of using liquid dosage forms in patient therapy. Describe pharmaceutical solutions components, solvent, drug, excipients and the role of each component. Compare between different traditional terms for different pharmaceutical solutions. Evaluate and select a proper solvent and excipients for a given solute, purpose, and/or patient population. Describe proper labelling of pharmaceutical product 3  INTRODUCTION Pharmaceutics: It is the science that involves the design and manufacture of drugs (API) and its appropriate dosage forms to be delivered safely, effectively and conveniently to the patient. 4 LIQUID DOSAGE FORMS Liquid dosage forms are dosage forms (pharmaceutical formulations that contain one or more APIs and excipients in a liquid state. These might be: ✓ Solution (Aqueous or Non-aqueous) ✓ Suspension ✓ Emulsion (W/O or O/W) Intended for: ✓ Internal use ✓ External use 5  DOSAGE FORMS Liquid Dosage forms Solution Suspension Emulsion Semi solid Dosage Forms Ointment Cream Gel Active Pharmaceutical Ingredient Solid Dosage Forms Powder & Granules Tablets Capsules 6 ADVANTAGES AND DISADVANTAGES OF LIQUID DOSAGE FORMS Easy to administer (Children & geriatrics) Accurate dosing Advantages Fast acting Versatility Taste issues Limited stability Disadvantages Difficulty in administering to certain populations Inconvenient for travel and difficult transportation 7 8  PHARMACEUTICAL SOLUTIONS A solution is a homogeneous, molecular, mixture of two or more components. The simplest solution consists of two components. A solute dissolved in a solvent. The solute and the solvent could be in the solid, liquid or gaseous states. Pharmaceutical solutions are preparations in which the solid solutes, i.e. Drug and excipients, are dissolved in a liquid solvent system. 9  PHARMACEUTICAL SOLUTIONS Solutions are one of the oldest pharmaceutical formulations. They are administered by many different routes: (e.g. Oral, otic (ear), parenteral). While all pharmaceutical solutions must be stable, and acceptable to patients, other requirements of solutions administered by the different routes vary. Solutions are classified by the nature of the formulation, or by the traditional name which relates to the solvent system used, such as syrups, elixirs, spirits and tinctures. 10  TRADITIONAL TERMS FOR DIFFERENT PHARMACEUTICAL SOLUTION Aromatic waters: saturated aqueous solutions of volatile oils or other aromatic or volatile substances. Elixirs: many solutions that contain alcohol as a cosolvent have traditionally been designated as elixirs. Spirits: alcoholic or hydro-alcoholic solutions of volatile substances. Some spirits are used as flavouring agents, others are medicinal. Tinctures: alcoholic or hydro-alcoholic solutions prepared from vegetable materials or chemical substances 11  TRADITIONAL TERMS FOR DIFFERENT PHARMACEUTICAL SOLUTION Syrups: oral aqueous solutions containing high concentrations of sucrose or other sugars. ‘Syrup BP’ is a solution of sucrose (66.7%) in purified water; it promotes dental decay and is unsuitable for diabetic patients. ‘Sugar-free’ syrups are obtained by replacing sucrose with hydrogenated glucose, mannitol, sorbitol, xylitol, etc. 12 ADVANTAGES OF PHARMACEUTICAL SOLUTIONS Solutions have several advantages,, ✓A solution may be the only available dosage form for many drugs. ✓Drug is already dissolved in the solvent system, hence rapid drug action, allowing their use in emergencies. ✓ The use of adrenaline solution, as an injection, for the treatment of anaphylaxis. ✓Solutions provide dose uniformity, and specific volumes of the liquid solutions that can be measured accurately; this allows a range of different doses to be easily administered. ✓Oral solutions are easily swallowed and are beneficial for patients or whom swallowing may be difficult, e.g. Children and older people. ✓Solutions are easier to manufacture compared to other dosage forms. 13 DISADVANTAGES OF SOLUTIONS ❖ The disadvantages of solutions compared with other dosage forms include: ❖ Many drugs are inherently unstable, and instability is increased when a drug is present in solution. ❖ Many drugs are poorly soluble in water. ❖ Their formulation as a solution is challenging. ❖ Liquids are bulky and less easy for the patient to carry compared to solid dosage forms. ❖ Liquids are also more expensive to transport, which increases the medicine’s cost. ❖ The packaging of pharmaceutical solutions requires materials of higher quality. 14 PHARMACEUTICAL SOLUTIONS FORMULATION Drug Solvent Excipients (API) System 15  THE DRUG The drug could be a small molecule like aspirin, or a large biotherapeutic molecule, such as insulin or an antibodies. The drug is present as molecules or ions throughout the solvent. The drug concentration in a pharmaceutical solution is below its saturation solubility in order to avoid the possibility of drug precipitating out of the solvent as a result of subsequent temperature changes during storage and use. 16  THE SOLVENT SYSTEM Water is the most common solvent, although organic solvents are used in combination with water or on their own. All the components of a solution are dispersed as molecules or ions, and the solution is optically clear. Solutions can be prepared by simple mixing of the solutes with the solvent system. In industry, solutions are prepared in large mixing vessels which are thermostatically controlled (desired specific temperature). 17 Pharmaceutical Solvents and Their Properties Alcohols Water Alcohols, such as ethanol Water is the most common and versatile solvent and propylene glycol, are used in pharmaceutical solutions, owing to its widely used in solution safety, availability, and ability to dissolve a wide formulations. They can range of polar and ionic compounds. improve solubility, stabilize certain active ingredients, and provide antimicrobial properties. Glycerin Oils Glycerin, or glycerol, is a polyhydric alcohol Non-polar solvents, such as used as a solvent, humectant, and viscosity- mineral oil and vegetable modifying agent in pharmaceutical solutions, oils, are utilized in solution particularly topical and oral formulations. formulations for lipophilic (fat-soluble) drugs and topical applications.  THE SOLVENT SYSTEM: WATER Water is the most commonly used solvent due to lack of toxicity and low cost. Different types of ‘water’ have been defined in the pharmacopoeias, related to its purity. Those defined in the British pharmacopoeia are given as representative examples 19  THE SOLVENT SYSTEM: DIFFERENT TYPES OF WATER (BP) Type of water Use Purified Water Used for the preparation of medicines that do not have to be sterile and apyrogenic. Highly Purified Water Used for the preparation of medicines where water of high biological quality is needed, except where Water for Injections is required. Water for injections Used for medicines for parenteral administration. Must be pyrogen-free. Sterile water for injections Used for medicines for parenteral administration. Water has been sterilized by heat and is suitably packaged 20  THE SOLVENT SYSTEM: Water Tap (drinking) water is not normally used for the manufacture of pharmaceutical solutions or for extemporaneous compounding. As it contains dissolved substances which could interfere with the formulation (reduce drug solubility and stability). Tap water is therefore purified, by distillation, ion exchange or reverse osmosis to produce purifed water. 21  THE SOLVENT SYSTEM: Water Reverse Osmosis is used for the preparation of non-parenteral solutions. For parenteral solutions, water is further purifed in order to remove pyrogens (water-soluble, fever producing compounds) thereby producing water for injections. In certain instances, for example, in extemporaneous dispensing, drinking tap (potable) water, freshly drawn from a mains supply, boiled and cooled, can be used to prepare oral or external solutions that are not intended to be sterile. 22  THE SOLVENT SYSTEM: CO-SOLVENTS Water does not dissolve many drug compounds to a sufficient degree to enable the preparation of a pharmaceutical solution. Other water-miscible liquids with greater drug solubility may therefore be added to water to enhance drug solubility. These liquids are called co-solvents. Co-solvents are generally less safe than water and the concentration used in an aqueous solution is limited primarily by their toxicity and cost. 23  THE SOLVENT SYSTEM: CO-SOLVENTS Most water-miscible organic liquids are toxic, and only a few are used as cosolvents in pharmaceutical solutions. Typically, a linear increase in co-solvent fraction results in logarithmic increases in drug solubility. The concentration of the co-solvent is however limited by its physiological acceptability. The co-solvent must be non-toxic at the concentrations used, and by the route of administration. Alcohols, including polyhydric ones: Ethanol, Propylene glycol, Glycerol, low MWT polyethylene glycols (PEGs) are often used as a co-solvent in oral, topical and parenteral solutions. 24  THE SOLVENT SYSTEM: CO-SOLVENTS Co-solvents are often used to increase the water solubility of drugs which do not contain ionizable group(s) and whose solubility can thus not be increased by pH adjustment. The principle ‘like dissolves like’. That is, polar drugs generally dissolve in polar solvents and non-polar drugs generally dissolve in non-polar solvents. Thus, non-polar drugs are poorly soluble in water – a polar solvent. To increase the solubility of such drugs in water, the latter’s polarity should be lowered. This can be achieved by adding a third component such as a water-miscible organic liquid with a low polarity ( a co-solvent). 25  THE SOLVENT SYSTEM: NON-AQUEOUS SOLVENTS Nonaqueous solutions are however limited to certain delivery routes, such as intramuscular and topical, due to their unpalatability, toxicity, irritancy or immiscibility with physiological fluids. Dimethyl Sulfoxide used as a carrier for Idoxuridine for topical application to the skin. Glycofurol used as a co-solvent in parenteral solutions for intramuscular or intravenous injection. 26  THE SOLVENT SYSTEM: NON-AQUEOUS SOLVENTS EXAMPLES Fixed oils are non-volatile oils and are mainly triglycerides of fatty acids: olive oil, corn oil, sesame oil, almond oil, poppyseed oil, soya oil, cottonseed oil, castor oil have been used for IM administration. They are used to a lesser extent now due to their irritancy and the possibility of allergic reactions to certain oils. They are being replaced by synthetic alternatives (Esters) such as ethyl oleate, benzyl benzoate. 27 EXCIPIENTS USED IN PHARMACEUTICAL SOLUTIONS Function Requirement Examples Enhance product Stable, cost effective Flavoring agent stability, Inert, nonirritant Colouring agent bioavailability. Compatible with Preservatives Enhance product formulation Antioxidants appearance. Suitable for the pH adjusters Aid product route of Isotonicity adjusters manufacture and administration (SLS Viscosity enhancers identification. in topical vs oral) Chelating agents 28 EXCIPIENTS: FLAVOURING AGENTS Flavouring agents used to mask the taste of drugs, many of which have a very unpleasant taste. Flavouring agent should be soluble, stable, inert and compatible with preparation. Sweeteners : sucrose, invert syrup, sorbitol, mannitol, xylitol, high fructose corn syrup, saccharin sodium, are used to improve the palatability of oral solutions. Sweetened, but sugar-free, preparations containing aspartame are suitable for diabetic patients. 29 EXCIPIENTS: FLAVOURING AGENTS Synthetic or natural flavourings such as vanilla, cinnamon, clove raspberry, orange oil, lemon oil are used for oral solutions. Menthol is used in both oral and nasal solutions. Certain flavours appeal to certain patient populations and certain parts of the world; this must be borne in mind by the formulator. For example, fruit and bubble gum flavours are acceptable to children, whilst mint flavour is not. 30 EXCIPIENTS: COLOURING AGENTS Colouring agents: A colouring agent is used to increase acceptability to patients, It should correlate with the flavoring agent, green with mint, red with cherry flavour. Its colouring power is high so only small Its safe and have no Its easily available quantities are activity and inexpensive required Its unaffected by Its free from light, temperature, unacceptable taste microorganisms and odour therefore stable on storage 31  EXCIPIENTS: COLORING AGENTS All colouring agents used in pharmaceutical formulations must be approved and certified by the Health regulatory authority. Refer to FDA in US and FD&C (Food Drug and Cosmetics Act). Vegetable Colors: Chlorophyll, Carotene Mineral Colors: Titanium dioxide, ferric oxides Synthetic Colors FD&C Red no.3 (Erythrosine), D&C Red no.22 (Eosine) FD&C Yellow no.5 (Tartrazine), D&C Yellow no7 (fluorescein) D&C Blue no.5 (indigo) FD&C Green no.3 (Fast Green) 32 EXCIPIENTS: OTHERS Antimicrobial preservatives used to preserve multidose preparations. Examples include benzalkonium chloride, benzyl alcohol, chlorobutanol, thimerosal, combinations of parabens (methyl, propyl, butyl). Antioxidants sodium metabisulphite, sodium sulphite, sodium bisulfate, ascorbic acid, used to stabilize solutions. pH adjusters : acids, e.g., citric acid, bases, e.g., sodium hydroxide, and buffers. Isotonicity adjusters: sodium chloride, potassium chloride, mannitol, dextrose, glycerol. Viscosity enhancers: hypromellose, hydroxyethylcellulose, polyvinyl alcohol, dextran, carbomer 940. Chelating agents: disodium edentate, used to increase solution stability. 33 Labelling To meet today’s FDA regulations, labeling information on drugs must include the following in this order: – Product Name – Drug Facts Table – Active Ingredients – Purpose and Use – Warnings – Directions – Allergic Reactions – Inactive Ingredients 34 Labelling The label must remain in place on the container and be legible across its lifespan, including distribution, storage and use. The printing on the label must also be legible across this lifespan. (This means you need to use labels that have strong adhesive strength and are resistant to water and UV light.) 35  Labelling To clarify drug information, the FDA requires that all pharmaceutical product labels include a “Drug Facts” table. This table is modeled after the “Nutrition Facts” label found on food containers and contains several pieces of standard information: Active Ingredients – The drugs and their amount per dosage. Uses – What medicine is intended to treat. Directions – How to take the medicine. Other Information – This covers important information that doesn’t fit in the previous categories. This is the area to list storage instructions. Inactive ingredients – Everything in the product that isn’t medicine. 36  Labelling Warnings – This section is divided into several statements. The “Do Not Use” statement covers warnings for medicine that shouldn’t be used unless prescribed by a doctor or shouldn’t be used by some consumers if they have a specific illness or symptom. The “Ask a Doctor” or “Ask a Doctor or Pharmacist” statement advises consumers on when they should talk to a medical professional before continuing the use of the drug. “When Using This Product” covers side effects and drug interactions. Common statements include “May Cause Drowsiness” and “Avoid Alcoholic Drinks.” “Stop and Ask a Doctor If” covers side effects and signs of toxicity to watch out for. Likewise “Stop Using If” is used for side effects that indicate the consumer should stop use immediately. “Keep Out of Reach of Children” must be used on most drugs. However, a few products are generally exempt, like makeup that contains sunscreen. 37 38