Midterm Exam - Powder, Tablet, Capsule, and Solution PDF

**POWDERS** - Type of pharmaceutical preparation, that is, a medicated powder intended for internal (i.e. oral powder), or external (i.e. topical powder) use. - A powder is defined as a dosage form composed of a solid or mixture of solids reduced to a finely divided state and inten...

**POWDERS** - Type of pharmaceutical preparation, that is, a medicated powder intended for internal (i.e. oral powder), or external (i.e. topical powder) use. - A powder is defined as a dosage form composed of a solid or mixture of solids reduced to a finely divided state and intended for internal or external use - Applications: - For internal use, they can be taken orally, administered through the nose as snuffs, or blown into a body cavity as an insufflation - For external use, solid powders can be applied to compromised areas of the body - Powders have also been used to make solutions for topical and oral use and for use as douches - Powders containing a bioadhesive material can be applied to a specific body area such that medication will adhere for a prolonged drug effect ***Two Advantages*** - Flexibility in compounding -- easily alter the quantity of medication for each dose. Powders can also aid in clinical studies of drug preparations because the dose can be so readily adjusted. Doses can be individually weighed and placed in powder papers, envelopes, or small vials/bottles ("Powder in a bottle" research studies are an example). In another example, infants and young children who cannot swallow tablets or capsules will accept powders that can be mixed with a formula or sprinkled in applesauce of some other appropriate food. - Relatively good chemical stability ***Disadvantages*** - Time consuming to prepare - Inaccuracy of dosage - Unpleasant tasting ***Types of Powders*** 1. Topical powders 2. Insufflated powders 3. Medicated powders -- aerosol powders 4. Bulk powders 5. Divided powders - Commonly prepared as divided powders or bulk powders - DIVIDED POWDERS are dispensed in individual doses and packed in papers, pouches, or other containers - Sodium bicarbonate powders - BULK POWDERS are mixed with water or other suitable material prior to administration - Powder for suspension - Examples - Oral powders - Dentifrices - Dusting powder **SMALL SCALE PREPARATION** 1. Trituration/Comminution 2. Pulverization by Intervention -- process of reducing the state of subdivision of solids with the aid of an additional volatile materials. Example: camphor with the aid of alcohol; comminution of iodine crystals in the presence of a small quantity of ether 3. Levigation -- particle size reduction is accomplished by rubbing the paste in a mortar with a pestle or an ointment slab using a spatula **LARGE SCALE PREPARATION** 1. Fitzmill comminutor 2. Tumbling 3. Mixing/Mixer 4. V-blender **What is a Tablet?** - Tablets are traditionally circular or disk shaped, but can resemble any shape. - Tablets which resemble a capsule is known as caplets and are designed to make swallowing easier for patients - A scored line is sometimes provided in the middle of the tablet to make them easier to break in half, if half a dose is required ***Types of Tablets*** - Compressed tablets - Sugar coated tablets - Film coated tablets - Enteric coated tablets - Effervescent tablets - Chewable tablets - Dispersible tablets - Sustained release tablets - Multiple tablets - Sublingual tablets - Buccal tablets - Implant tablets - Hypodermic tablets - Solution tablets - Vaginal tablets **Excipients** ***Diluents*** - Are used to increase the bulk content of the dosage form - Examples: - Sugar compounds e.g. lactose, dextrin, glucose, sucrose, sorbitol, inorganic compounds (e.g. silicates, calcium and magnesium salts, sodium, or potassium chloride, cornstarch ***Binders*** - Binds or glues the tablet ingredients together giving form and mechanical strength - Examples - Mainly natural or synthetic polymers (e.g. starches, sugars, sugar alcohols, and cellulose derivatives) ***Disintegrants*** - Added to the formulation as it breaks the dosage form into smaller particles and when it comes in contact with the liquid - Examples - Compounds which swell or dissolve in water e.g. starch, cellulose derivatives, and alginates, tragacanth, gelatin ***Lubricant*** - Act by reducing friction by interposing an intermediate layer between the tablet constituents and the die wall during compression and ejection - Examples: - Stearic acid and its salts (e.g. Mg stearate) ***Tablet coating and Films*** - Protect the tablet from the environment (air, light, and moisture), increase the mechanical strength, mask taste and smell, aid swallowing, assist in product identification - Can be used to modify release of the active ingredient - May contain flavours and colourings - Sugar (sucrose) has now been replaced by film coating using natural or synthetic polymers - Polymers that are insoluble in acid - E.g. cellulose acid phthalate are used for enteric coatings to delay release of the active ingredient ***Coloring agents*** - Improve acceptability to patients, aid identification, and prevent counterfeiting, increase stability of light sensitive drugs - Used to impart color to liquid and solid preparations - Examples: - Caramel, ferric oxide, FD&C Red No. 3, FD&C Red No. 20, FD&C Yellow No. 6, & FD&C Blue No. 2 ***Anti-adherents*** - Avoid sticking to die walls and picking by punches - Examples: - Talc, cornstarch, colloidal silica ***Plasticizer*** - Components of film coating solutions to make film more pliable, enhance spread of coat over tablets, beads, and granules - Examples: - Diethyl phthalate, Glycerin ***Tablet Opaquant*** - Used to render a coating opaque, may be used alone or with colorant - Examples: - Titanium dioxide ***Tablet Polishing Agent*** - Used to impart an attractive sheen to coated tablets - Examples: - Carnauba wax, white wax ***Antioxidant*** - Used to prevent deterioration of preparations by oxidation - Examples: - Ascorbic acid, Ascorbyl palmitate, Propyl gallate, Sodium bisulfite, Sulfoxylate, Sodium metabisulfite **WET GRANULATION** The most widely used process of agglomeration in pharmaceutical industry is wet granulation. Wet granulation process simply involves: - Wet massing of the powder blend with a granulating liquid - Wet sizing - Drying **Important steps involved in the wet granulation:** - Weighing and blending the ingredients - Preparing a dampened powder or a damp mass - Screening the dampened powder or damp mass into pellets or granules - Drying the granulation - Sizing the granulation by dry screening - Adding lubricant, blending, and - Forming tablets by compression **DRY GRANULATION** In dry granulation process, the powder mixture is compressed without the use of heat and solvent. It is the least desirable of all methods of granulation. The two basic procedures are to form a compact of material by compression and then to mill the compact to obtain granules. ***Two methods are used for dry granulation:*** - **Slugging** -- where the powder is recompressed and the resulting tablet or slug are milled to yield the granules - ***Precompress*** -- the powder with pressure rolls using a machine such as Chilosonator ***Steps in dry granulation:*** - Milling of drugs and excipients - Mixing of milled powders - Compression into large, hard tablets to make slug - Screening of slugs - Mixing with lubricant and disintegrating agent - Tablet compression Process This method is used when a group of ingredients can be blended and placed in a tablet press to make a tablet without any of dry ingredients having to be changed. This is not very common because many tablets have API which will not allow for direct compression due to their concentration or the excipients used in formulation are not conducive to direct compression. **Ribbon Mixer Machine** - An efficient and versatile blending machine for mixing of dry granules & powders homogenously - The Ribbon mixer gives best result for mixing of dry powders & granules due to the design and shape of the mixing ribbon and product container  Sigma type blades - Sigma type blades are rotates in same direction along horizontal axis. Suitable for powder, semisolid material **Rapid Mixer Granulator**  - Prevent segregation of ingredients in the mixture and improves the compression characteristics of the mixture **Fluid Bed Dryer Machine** - Used in granulation process for drying the material to get desired moisture content in the tablet formulation granules **Double Cone Blender**  - An efficient and versatile machine for mixing dry powder and granules homogenously - The materials to be mixed are placed inside the conical chamber and rotate along its horizontal axis - These machines have a cylindrical shell with two conical frustums provided with opening for charging and discharging **V-Blender Machine** - V-Blender is as the vessel rotates from the V position, the batch is divided into right and left legs. As the vessel continues its rotation, the batch blends and recombines. - The materials are placed in the V-shaped chamber and rotate on its horizontal axis. Due to tumbling action, materials are mixed uniformly. - As the V-blender tumbles, the material continuously splits and recombines, with the mixing occurring as the material free-falls randomly inside the vessel. - The repetitive converging and diverging motion of material combined with increased frictional contact between the material and the vessel's long, straight sides result in gentle yet homogenous blending **Spray Coating Machine**  - Used for tablet coating where by tablets are coated with either cellulose based film or sugar coat - The coating is achieved by spraying a solution or suspension of the coating material onto the tablet in the form of fine droplets and at the same time pass a flow of heated air oven the tablets **Rotary Tablet Press Machine** No alternative text description for this image - Tablet Rotary Press is the mechanical device with multiple punches that rotates to compress the powder into tablets of uniform size with different shape and uniform weight to yield more number of tablets than single punch machine  **Blister Packing Machine** - Blister Packing Machine are automatic machine mainly utilized for packing of smaller and regular shaped solid articles such as pharmaceutical tablets, capsules, in blister packs. - The Blister Forming, Product Feeding, and Sealing Operations are continuous by rotary motion while the indexing and punching operations are of intermittent reciprocating motion. - The output capacity of the machine depends on the product characteristics and thus on the type of feeding device.  Example: Formulation - Aspirin - Cornstarch - Talc - Magnesium stearate - Distilled water **CAPSULES** **Advantages** - Capsules are tasteless, odorless, and can be easily administered - There are attractive in appearance - The drugs having unpleasant odor and taste are enclosed in a tasteless shell - They can be filled quickly and conveniently - Physician can change the dose and combination of drug according to patient requirement - They are economical - They are easy to handle and carry **The two main types of capsules are:** **Hard shell capsules** -- which are typically made using gelatin and contain dry, powdered ingredients or miniature pellets made by e.g. processes of extrusion or spheronisation, the process used to create solid particles in a uniform shape. Capsule sizes 000 (largest) to 5 (smallest). Moisture content is 12-16%. With body and cap, can be used in extemporaneous compounding **Soft-shelled capsules** primarily used for oils and for active ingredients that are dissolved or suspended in oil. **Ingredients of Capsules:** - Empty gelatin capsules contain only high-quality beef gelatin and purified water. - White capsules also include natural mineral Titanium dioxide as color. - Empty vegetable capsules (also referred to as empty vegetarian capsules) consists of only two ingredients HPMC and water, - HPMC (Hydroxypropylmethylcellulose) -- is derived from vegetable cellulose, 100% natural, these capsules contain no preservatives, gelatin, wheat, animal by-products or starch, and they are made from pure cellulose of either pine or poplar. **Characteristics of capsules:** - Capsules should be stored in a cool (Temperature 58-79°F), dry place (Humidity between 455 and 60%). Expiration date of the capsules is 5 years. **CAPSULE SHELL** The capsule shell is basically composed of gelatin, a plasticizer, & water it may contain additional ingredients such as preservative, coloring, & opacifying agents, flavorings, sugars, acids, & medicaments to achieve desired effects. 1. Capsule shell WATER NMT 45% w/w the ratio by weight of water to dry gelatin can vary from 0.7 to 1.3 ratio (water) to 1.0 (gelatin) depending on the viscosity of the gelatin being used. 2. PLASTICIZER Used to make the soft gel shell elastic & pliable. Ratio used is between 0.3 to 1.8 for soft to hard shell on dry basis. E.g. glycerin, sorbitol 3. COLOR Used in shell has to be darker than color of encapsulating material colors may be natural or synthetic 4. OPACIFIER Usually Titanium dioxide, may be added to produce an opaque shell, when the fill formulation is a suspension or to prevent photo degradation of light sensitive fill ingredients. Concentration of opacifier may be up to 0.5% 5. CHELATING AGENTS Iron is always present in raw gelatin & should not contain iron more than 15 ppm. Additionally, chelating agent may be used for prevention of iron with materials or colors **Manufacture of Hard Gelatin Capsules** 1. Dipping 2. Spinning 3. Drying 4. Stripping 5. Trimming and Joining 6. Polishing **Ingredients of Dosage Form in capsule** **Binders** -- used to help the tablet together after compression Ex. Starch and gelatin **Lubricants** -- used to make the powder flow in the tablet machine and to lubricate the steel punches and dies Ex. Talc, Mg stearate **Diluent** -- used to add volume to the tablet to increase its size Ex. Lactose, Starch **Disintegrants** -- to assist break up & distribute content in stomach **Glidants** -- aids for the free flowing properties **Surfactants** -- facilitate wetting **HAND OPERATED CAPSULE FILLING MACHINE** Tamper Proof Manual Hand Operated Capsule Filling Machine, For Pharmaceutical Industry, Capacity: 6000-12000 Capsules/Hour ***Procedure**:* - Plates for putting of capsule by hand - Removal of caps - Filling of powder by dispensing of brush pressing - Fixing of caps and sealing - Injection of capsules - Contact parts of stainless for 100 capsules of size 00 **SEMI AUTOMATIC CAPSULE FILLING MACHINE**  ***Procedure:*** - Take the cap sheet. Place it on a clean, dry surface - Place the encapsulation sheet on top of the cap sheet using the black pegs to fix it correctly in place - Pour capsule tops into the encapsulation sheet and using a circular motion; gently shake the tops into the holes. While doing this, cover the gap in the wall of the encapsulation sheet with one hand to avoid splitting the tops. - When the holes are filled, pour out the excess tops - Remove the encapsulation sheet and put the filled cap sheet to one side - Now take the bottom sheet. Fix the encapsulation sheet to the bottom sheet, using the black pegs to fix it correctly in place. - Pour bottoms into the encapsulation sheet and shake as before to fill the holes. Pour off excess bottoms - Remove the filled encapsulation sheet and put it carefully to one side - Pour a soop of powder filler onto the bottom sheet and use the spreader to fill the bottoms. Remove the spreader and put it to one side. - Take the filled cap sheet and place the middle sheet on top using the black pegs to fit it correctly in place. - Turn the cap sheet/middle sheet over and fix to the bottom sheet. Using hands and equal pressure, press down once to fit both parts of the capsule together. **AUTOMATIC CAPSULE FILLING MACHINE** ***Procedures:*** - The housing and surface are covered with stainless steel 304. All contact parts of medical powders are made from a corrosion resistant stainless steel 316 - Parts are made by CNC computer machine. All parts are standardized and easy to substitute. - Capable of filling 6 capsules at a time with operation from 10 stations. Accurate operation for orientation, opening, filling, joining, and ejecting of the capsules. - Compulsory spiral feeding in the powder hopper to ensure powder feeding and filling. - Dual capsule-opening design to ensure all capsules are opened. - Electrical impact protection device to prevent any further damage. The machine will stop automatically in the event of collision. - Safety Sensing System to shut the machine down automatically in the event of problems when no capsules, no powder, door is opened, and abnormal load for the machine are detected. - Automatic vacuum removal of the air in the dosing tube to give more accurate weight of the filled capsules - Exclusive dosing tube system, temperature of the powder will not rise during the filling process - Adjustable compression piston in dosing tube to adjust the powder volume without change parts - Easy to change the molds without alignment. A person without experience can change the molds within 30 minutes  ***Procedures:*** - Empty capsule storage hopper; holds the empty capsule shells - Rectifier: rectifies the capsules - Faulty capsules are removed and checked by a vacuum system, which provides a signal upon feed interruption - Bulk powder storage hopper: holds the bulk powder and delivers following AUGER principle - Capsule body transport system: holds the separated bodies and caps individually and transports to various working stations **Soft Gelatin Capsule** - One piece - Made of gelatin, glycerin, or polyhydric alcohol such as sorbitol - More moisture - With preservative - Elegant - Easy to swallow **Manufacture of soft gelatin capsules is manufacturing by four (4) methods** - Plate process - Rotary die process - Reciprocating die - Accogel machine **ROTARY DIE MACHINE** Parts of softgel encapsulation machine Rotary die process to be encapsulated flows by the gravity the gelatin sheets are feed on rolls contain small orifice lined up with the die pocket of the die roll Two plasticized gelatin ribbons are continuously and simultaneously fed with the liquid or paste fill between the rollers of the rotary die mechanism where the capsule are simultaneously filled, shape, hermetically sealed and cut from the gelatin ribbons. The sealing of the capsule is archived by mechanical pressure on the die rolls and the heating (37-40°C) of the ribbons by the wedge. **Norton Capsule Machine**  **Accogel Capsule Machine** **Filling of capsules** **Dry solid** -- powder, pellet, granules or tablet, caplet, etc. **Semisolids** -- non-aqueous **Liquid** -- non-aqueous liquids **PHARMACEUTICAL PREPARATION OF SOLUTION** ***Ingredients, Functions, and Uses of Solution*** **SOLUTIONS** In pharmaceutical terms, solutions are "liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvent. **Classified for their use:** - Oral - Otic - Ophthalmic - Topical **Classified of their composition/use:** - Syrup (water & sugar) - Sweetened hydroalcoholic (syrup & alcohol) - Elixir (water & ethanol) - Spirit (aromatic materials & alcohol) - Aromatic waters (aromatic materials & water) - Tinctures (extract & alcohol) - Injections (sterile and pyrogen-free) and intended for parenteral administration **Some solvents for liquid preparations:** - Alcohol (ethyl alcohol, ethanol) - Diluted alcohol - Glycerin - Isopropyl alcohol - Propylene glycol - Purified water, USP **The main methods used in the preparation of purified water are:** - Distillation - Ion exchange (demineralized or deionized), and - Reverse osmosis **Preparation of SOLUTIONS** - Solution of the ingredients with the aid of heat - Solution of the ingredients by agitation without the use of heat, or the simple admixture of liquid components - Addition of medicating liquid, such fluidextracts, tinctures or other liquids - Percolation of either the source of medicating substance or the sucrose Advantages Disadvantages ------------------------------------------------ ------------------------------------------------------------- Drug available immediately for absorption Drug stability often reduce in solution Flexible dosing Difficult to mask unpleasant tastes Maybe designed for any route of administration Bulky, difficult to transport and prone container breakages Facilitates swallowing in difficult cases Measuring device/s needed for administration **Humectants** - Substance used to keep products moisturized and affects the preservation of the products - Examples: - Propylene glycol - Hexylene glycol - Glyceryl triacetate - Butylene glycol **Acidifying agent** - Used in liquid preparation to provide acidic medium for product stability - Examples: - Citric acid - Acetic acid - Fumaric acid - Hydrochloric acid **Alkalinizing agent** - Used in liquid preparation to provide alkaline medium for product stability - Examples: - Ammonia solution - Ammonium carbonate - Diethanolamine - Monoethanolamine - Potassium hydroxide **Solvent/Co-solvent** - Are chemical substance that can dissolve, suspends, or extract other materials usually without chemically changes either the solvent ir the other materials. Solvents can be organic, meaning the solvent contains carbon as part of its makeup, or inorganic, meaning the solvent does not contain carbon Examples: - Ethanol - Peanut oil (e.g. IM injection) - Isopropyl alcohol - Water Note: hydrocarbon & oxygenated solvent -- effective to dissolve many materials **Antioxidant agent** - Also known as protecting agents; are substance which are added to solution used in pharmaceutical products and preparation to prevent chemical oxidation caused by exposure to oxygen - Examples: - Ascorbyl palmitate - Monothioglycol - Ascorbic acid **Buffering agent** - Necessary to maintain pH of the formulation in order to: - Ensure physiological compatibility - Maintaining/optimizing chemical stability - Maintaining/optimizing anti-microbial effectiveness - Optimizing solubility (or insolubility if taste is an issue) - Examples: - Magnesium oxide (MgO) - Calcium carbonate (CaCO3) - Disodium phosphate - Monosodium phosphate **Anti-microbial agent** - Used to prevent an increased risk of contamination and proliferation by opportunistic microbes (from excipients or introduced externally) - Examples: - Benzoic acid - Benzyl alcohol - Sodium benzoate - Thimerosal - Benzalkonium chloride - Parabens (methylparaben, propylparaben, butylparaben) **Wetting agent** - Used to reduce the interfacial tension between solid and liquid during manufacturing or reconstitution of a suspension - Examples: - Polysorbates Tweens & Sorbitan esters Spans (ORAL) - Polysorbates, Poloxamers, Lecithin (PARENTERAL) **Anti-foaming agent** - Are effective at discouraging the formation of stable foams by lowering surface tension and cohesive binding of the liquid. - Examples - Simethicone (polydimethylsiloxane-silicon dioxide) - Ethylhexanol - Ammonium dimolybdate - Oleic acid **Thickening agent** - Or suspension stabilizer prevent setting/sedimentation (particularly if a wetting agent is present) - Examples - Sodium alginate - Potassium alginate - Agar (E406, a polysaccharide obtain from red algaes) - Gelatin (E441, made by partial hydrolysis of animal collagen) - Carrageenan (E407, a polysaccharide obtain from red seaweeds) **Sweetening agent** - Used to incorporate sweet paste in the pharmaceutical products. - Examples - Saccharin sodium - Aspartame - Sorbitol - Mannitol - Glycerin **Flavoring agent** - Used to mask the unpleasant taste of the pharmaceutical products. - Examples: - Bitter -- mint, cherry, and anise - Salty -- peach, apricot, and liquorice - Sour -- raspberry, liquorice - Sweet -- vanilla **Solubilizer** - Substances that increase the solubility and the availability of the API in a medication. These are usually added in Parenteral Dosage Form - Examples: - Propylene glycol - Plasdone C - Cyclodextrin - Plasdone K polymer **Dyes and colorants** - Added to improve the appearance of a formulation. Manufacture also use these as an identification of their products. - Examples: - FD&C Blue No. 2 - FD&C Red No. 3 - FD&C Yellow No. 6 - D&C Orange No. 5 - D&C Green No. 5 - Canthaxanthin caramel **Viscosity-increasing agent** - Used to render preparations more resistant to flow. - Examples: - Alginic acid - Bentonite - Carbomer - Carboxymethylcellulose Sodium - Methyl cellulose - Povidone - Sodium alginate - Tragacanth **Classification of Solutions** 1. **Aqueous solution** - Aromatic water - Aqueous acids - Hydracids -- do not contain oxygen e.g. Hydroiodic, Hydrochloric - Oxygen containing acids -- e.g. Nitric acid - Douches - Enemas - Gargles - Washes - Juices - Sprays - Sweet or other viscid aqueous solution - Syrup - Simple syrup -- 65% by weight - Medicated syrup -- syrup containing medicinal substance - Flavored syrup - Honeys - Mucilages - Jellies 2. **Non-aqueous solution** - Alcoholic or hydroalcoholic solutions - Elixirs - Spirits - Ethereal solutions - Collodion - Glycerin solution - glycerites - Oleaginous solution - Liniments - Oleovitamins - Toothache drops - Medicated solution for vaporization - Inhalations - Inhalations or insufflations - Inhalants ***SYRUP*** - Are concentrated aqueous preparations of a sugar or sugar substitute with or without flavoring agents and medicinal substances. - Syrups containing flavoring agents but not medicinal substances are called nonmedicated or flavored vehicles (syrups) - Medicated syrups are commercially prepared form the starting materials, that is, by combining each of the individual components of the syrup, such as sucrose, purified water, flavoring agents, coloring agents, the therapeutic agent, and other necessary and desirable ingredients. - Components of syrup, antimicrobial preservatives, flavorants, colorants, may contain special solvents, including alcohol, solubilizing agents, thickeners or stabilizers. ***ELIXIR*** - Are usually prepared by simple solution with agitation by admixture two or more liquid ingredients. These are clear, pleasantly flavored, sweetened hydroalcoholic liquids intended for oral use. - Compared with syrups, elixirs are usually less sweet and less viscous *General components* - Ethanol - Water - Glycerin - Sorbitol - Propylene glycol - Flavoring - Preservatives - Syrup The presence of glycerin, sorbitol, syrup, propylene glycol in elixir contributes to the solvent effect solution of the solute, enhances the stability. ***TINCTURES*** - Tinctures cannot be mixed successfully with liquids too diverse in solvent character because the solute may precipitate. - For example, compound benzoin tincture, prepared with alcohol as the sole menstruum, contains alcohol -- soluble principles that are immediately precipitated from solution upon addition of water - Because of the alcoholic content, tinctures must be tightly stoppered and not exposed - to excessive temperatures. - Because many of the constituents found in tinctures undergo a photochemical change upon exposure to light, many tinctures must be stored in light -- resistant containers and protected from sunlight - Medicated tinctures taken orally include Paregoric USP or camphorated tincture of opium - Opium Tincture, USP, or laudanum, is much more potent than paregonic, and the two should not be confused. - Opium Tincture contains 10% opium (which equal to 1% morphine) and camphorated tincture of opium contains 0.4% opium (which equates to 0.04% morphine). - Any prescription for either one should be carefully evaluated and the dose checked and confirmed - However, Tinctures have a rather high alcohol content, and some physicians and patients alike prefer other forms of medication **Proper Administration and Use of Liquid Peroral Dosage Forms** - By mouth - Measured in a teaspoon or tablespoon - Measuring calibrated devices for correct dose - Recommended that the patient follow the administration of the liquid dosage form with a glassful of water - Syrups contains sugar would not be suitable for use in an oral prescription intended for a diabetic patient - Elixir or syrup containing alcohol would not be suitable for a patient who receives concurrent medicines that possess an Antabuse like activity; the patient may get violently ill from the concurrent ingestion of alcohol. - Metronidazole and chlorpropamide have been implicated to cause this reaction when mixed with alcohol - If the patient is receiving another drug that causes drowsiness, the pharmacist must consult the prescribing physician to determine whether the prescribed elixir could be harmful to the patient. - The topical solutions employ an aqueous vehicle, whereas the topical tinctures characteristically employ an alcoholic vehicle - As required, co-solvents or adjuncts to enhance stability or the solubility of the solute are employed - Preparation by simple dissolving, by chemical reaction, by maceration - Examples sprays, topical solution, medicated soaps and shampoo ***Vaginal and Rectal Solutions*** - Vaginal douches - Retention enemas **NON-AQUEOUS SOLUTIONS** - **Liniments** = are alcoholic or oleaginous solutions or emulsions of various medicinal substances intended to be rubbed on the skin. - **Collodions** = are liquid preparations composed of proxylin dissolved in a solvent mixture usually composed of alcohol and ether with or without added medicinal substances. **Extraction methods for Preparing Solutions** - **Maceration** - The term maceration comes from the latin "macerare," meaning to soak. - **Percolation** - The term percolation, from the Latin "per," meaning through, and "colare," meaning to strain **Examples: fluidextract and extract** **MANUFACTURING CONSIDERATIONS** ***Raw Materials*** - **Conforms to specifications** - Identity - Potency - Free form contaminations - **Water the most important constituents** - Should meet the USP requirements - Techniques are used such IV sterilization, no "dead ends" where microorganisms thrive  - Mixed resin bed would be Ambergard and Amberlite - Ultraviolet sterilization of water, factors to consider: - The flow rate of the water and its lifespan - Even if sterility is achieved, filter should be used downstream to remove dead microorganisms and particulate matters **Equipment** - Mixing tanks equipped with agitation - Measuring devices for **large amount** (ex. Dipsticks), for **small amount** (ex. Graduated kettle) - Filtration system - Final sterilization - Piping sterilization - Valves - All of these must be thoroughly cleaned and sanitized - Appropriate disinfectants dilutions of hydrogen peroxides, phenol derivatives - May sterilized by alcohol, boiling water, autoclaving, steam or dry heat - Mixing tanks equipped with agitation - Measuring devices for **large amount** (ex. Dipsticks), for **small amount** (ex. Graduated kettle) - Filtration system - Final sterilization - Piping sterilization - Valves - All of these must be thoroughly cleaned and sanitized - Appropriate disinfectants dilutions of hydrogen peroxides, phenol derivatives - May sterilized by alcohol, boiling water, autoclaving, steam or dry heat - Tanks are constructed of polished stainless steel (SS316 or SS316L) usually jacketed - Filtration system - Holding tank and filling tank should be minimum distance to avoid microbial contamination is transport - Lines should be easy to disassemble, clean, and sanitize - Operators should worn at all times gloves and masks - Ongoing education program or training are maintained Mixers and Agitators \| FluidPro **Compounding Procedure** - Step 1 measuring specific amount of purified water - Step 2 heated - Step 3 Mixing - Step 4 Filter **PACKAGING** **THREE BASIC FILLING MACHINE** - **Gravimetric filling** - to large containers or highly viscous products - **Volumetric filling** - positive displacement piston action, each filling station is equipped with measuring piston and cylinder, premeasured, same volume - **Constant level filling** - uses the containers as the means for controlling the fill of each unit, same level or **"fill-to-alevel"** method **Liquid Volumetric Filling** - Delivers a premeasured volume of product to each container, and the volume of product to each container, and the volume of product in each container is held constant - Volumetric filling can also be accomplished by the pumping of a liquid at a constant pressure through an orifice of constant size for a predetermined period of time - Types of volumetric filling: - Piston operation - Diaphragm action - Timed flow 1. **Piston Volumetric Filling** - A piston filler measures and delivers the product to the container by the action of a single piston for each filler head 2. **Diaphragm action** - Uses a flexible diaphragm and pneumatic pressure to move premeasured amounts of product from the supply tank into a controlled volume chamber and into the container  3. **Timed Flow Volumetric Filling** - The volume of product in each fill can also be regulated by controlling the amount of time the product flow at a constant rate through a standard sized tube into a container - Three popular ways of measuring and regulating the flow time are rotating metering discs, rotary pumps, and augers 1. **Rotating Metering Discs** - The filling head consists of two stationary plates and a bottom rotating plate - When the openings in the three plates are in alignment, the product is free to pass through into the container. The flow ceases when the rotating bottom plate moves out of position. 2. **Rotating Pumps** - Rotary pumps are used for volumetric filling by regulating the operating interval of the pump to control the amount of product that is delivered.  3. **Augers** - Semi - liquid products that are too thick to be moved by a rotary pump may be filled by a similar filler that uses an auger in place of the pump to move the product. - The volume of product delivered by an auger is controlled by the amount of time the auger turns or the number or turns it makes on each fill, in much the same manner that is used for rotary pumps. - Some auger fillers use an agitator rotating in the product hopper to keep the product moving smoothly and maintain an even consistency. **Liquid Constant Level Filling** - Uses the container as the means of controlling the fill of each unit - The fill amount is varied by adjusting the height to which container is filled - The oldest form of a constant - level filler is the use of siphon - 3 categories of this method: vacuum filling, gravity vacuum filling and pressure filling **Vacuum Filling** - To fill by vacuum, a seal must be made between filling head and the container - Vacuum is developed which causes the liquid to flow from the liquid to the container - The liquid level rises until it reached the vacuum tube  **Gravity Vacuum Filling** - The bulk liquid tank are level above pressure and gravity **Rotary Bottle Washing Machine** - Cleaning and washing  **Bottle Unscrambler Machine** No photo description available. **Liquid Filling Machine** - Specialized machines used to fill bottles, vials, ampules  **Volumetric Filling Machine** - Low to medium viscosity **Vacuum Filling Machine**  **Automatic filling machine** - Ensure filling without leakage. - No foam and damage bottle is no incorporated. **Semi-Automatic Volumetric Filling Machine** - Can be used in different types of glass, plastic, metal, containers  **High Speed Automatic Bottle Filling and Cap sealing machine** - Filling sequence for difference fill sizes - Filling head 4,6,8,... - 80 - 160 bottles per minute. - Connecting an online automatic bottle capping machine. **ROPP Cap Sealing Machine** - Roll on pilfer proof - Ideal for continuous heavy-duty operation **Bottle Labelling Machine**  **Bottle Cartoning Machine** EXAMPLE FORMULATION: LAGUNDI SYRUP - Lagundi leaf powder - Refined sugar - Glycerin - Propylparaben - Methylparaben - Citric acid - Orange Flavor - Distilled water