Reporting: Solution-tablets Flashcards

Question

New Design for Drug Formulation:

Answer 1

1. Dry powdered Inhaler-Allows medicine to get deep into the lungs. Unlike other inhalers which deliver a puff of medicine, these inhalers hold the medicine as a dry powder. Since the medicine sits inside as a powder, you have to breathe in fast and deep to get the medicine into the lungs. 2. Spherical crystallization (SC)-A promising technique which encompass the crystallization, agglomeration, and spheronization phenomenon in a single step. Initially, two methods, spherical agglomeration, and emulsion solvent diffusion, were suggested to get a desired result.

Answer 2

1. Mortar and Pestle - most commonly used small scale mixing equipment combines comminution & mixing in single operation 2. Tumbling mixers/blenders are most commonly used for powders with similar densities - are likely to mix powders with good flowability and granules, rather than cohesive or powders with poor flowability 3. Ribbon mixers - can mix powders with poor flowability and avoid segregation as compared to tumbling mixers. Spiral ribbons, paddles, or blades are mounted on a shaft, which is located in the center of the mixing equipment 4. Planetary Mixer - commonly called beater and is consists of an anchor type of paddle/agitator revolving in a cylindrical pot with a hemispherical base can break agglomerates easily. 5. Nauta Mixer - also called orbiting screw blender or vertical cone screw blender, composed of a bottom discharger with a rotating screw-fastened to the upper end of the rotating arm. In this equipment, the vertical impeller and horizontal rotating arm are combined together to induce a combination of convection, shear, and diffusive mixing. 6. Fluid bed mixer - usually used for powder mixing, prior to granulation in the same bowl. Efficient mixing is achieved by circulation of the fluidized powder.

Answer 3

• Acetylcysteine (Exflem) Powder for Oral Solution is used for secretolytics in cases of acute and chronic bronchopulmonary diseases. • ZEVTERA Ceftobiprole medocaril powder for injection - This medication contains an antibiotic from the cephalosporin family. Typically, it is used to treat infections. • KUVANO (sapropterin dihydrochloride) - Powder for oral soln, used to lower blood Phe levels in adults and children over one month of age with a certain type of Phenylketonuria (PKU).

Answer 4

Dissolution - rate of absorption depends on the dissolution of the product. It is directly proportional to the bioavailability of the products. Organoleptic Properties - Some tablets may contain organoleptic substances such as flavoring agent, coloring agent and sweetener. Color uniformity of the tablet can be evaluated by reflectance spectrophotometry, tristimulus colorimetry or micro reflectance photometry. Drug Content - Drug uniformity in tablet is determined by assay. It is calculated on batch to batch or lot to lot basis. It is estimated by the titration, spectrophotometer and HPLC. Hardness - Suitable hardness is necessary for handling during manufacturing, packaging and shipping. Hardness of the tablets can be measured by Monsanto tester, Strong-cobb tester, Pfizer tester and Erweka tester. Disintegration - Breaking of tablets into smaller particles or granules is known as disintegration and time taken for breaking of tablets in a suitable medium is called disintegration time (DT). Friability - measurement of tablet strength as tablet hardness is not an absolute indicator of strength. Weight Variations - measured to ensure that tablet contains the proper amount of drug and is a satisfactory test for determination of content uniformity of tablets. Usually, ten tablets are taken for this test.

Answer 5

1st step: in the tablet manufacturing process is a pre-formulation. The active ingredients and excipients that will be used in the tablet are mixed together in the correct proportions. 2nd step: is the formulation. It is when the tablet is created. Mixture from pre-formulation is placed into a tablet press, which forms it into the desired shape and size. After coating the tablet undergo 3rd step: final testing to ensure that they meet all the quality standards.

Answer 6

• Wet Granulation - commonly used for compressed tablet production. Involves a size enlargement process and adhesive substance known as binder. Manufacturing tablets that use this technique increases the chances of meeting all physical requirements for tablet formulation. Steps for a Successful Wet Granulation Tablet Manufacturing Process: 1. Weigh, mill, and mix your active pharmaceutical ingredients (APIs) with powdered excipients. 2. Prepare binder solution. 3. Mix your binder solution with powders to create a damp mass. 4. Wet screen the dampened powder into pallets or granules using mesh screen 5. Dry the moist granules. 6. Mix the dried granules with lubricant and disintegrants. 7. Compress the granules into tablets. • Dry Granulation - process works by compacting powder mixtures into large pieces or compacts and breaking them down into granules. This can be used to prevent drug substance exposure to elevated temperatures during drying or moisture. Its process eliminates several manufacturing steps but still requires weighing, mixing, slugging, dry screening, lubrication, and granule compression. Steps for a Successful Dry Granulation Tablet Manufacturing Process: 1. Weigh and mill formulation ingredients like drug substances and excipients. 2. Mix the milled powders. 3. Compress mixed powders into slugs. 4. Mill and sieve the slugs. 5. Compress them into tablets. • Direct Compression - A cost-effective way to develop tablets, and is a common solution for producing generic products in pharmaceutical industry. Directly compresses powdered materials into tablets without modifying physical properties. This avoids a wide range of wet and dry granulation problems. Steps for a Successful Direct Compression Tablet Manufacturing Process 1. Mill therapeutic agents and excipients. 2. Mix milled powders, disintegrants, and lubricants. 3. Compress the tablets.

Answer 7

* Hammer Mill - used in milling pharmaceutical raw materials, herbal medicine, and sugar. * Vibration Mill-used for grinding of almost all materials concerning processing industry, fromb medium-sized lumps up to extra-fine final grains. * Roller Mill-used in the preparation of ointment; paste, creams, and other semi solid preparations. * Pin Mill-kind of milling equipment that can break up cellular materials selectively without damaging the starch granules. * Fluidized Energy Mill-used for the fine grinding of frits, Kaolin, Zircon, titanium, and calcium, alumina. * End-runner Mill-provides moderately fine powder and operates successfully with fibrous materials, bark, woods, fruits, leaves, etc. * Edge Runner Mill-used particularly for reducing extremely tough and fibrous materials - roots and barks to the form of powder. * Cutter Mill-used for milling tough materials, fibrous materials prior to extraction, and produce coarse particles from dried granulations before tableting. * Ball Mill: a. Small and Average Capacity Ball Mills-used for the final grinding of drugs or for grinding suspensions. b. Maximum Capacity Ball Mills - used for milling ores prior to manufacture of pharmaceutical chemicals. * Weighing Balances - Bulk Weighing Balance- applicable for very high or low-density products, very high flow, or can be designed with a shape or size adapted to meet your requirements. - Electronic Weighing Balance - device used to measure mass or weight. *Mixing equipments - Pneumatic Mixers- used in mixing dry and free flow powders. - Diffusion/Tumbling Mixers- widely used for blending dry powders and granules, and used for mixing powders of different densities. - Convective Mixers- used for blending solids combined with its ability to perform heating, cooling, coating, and other processes. *Granulators - Dry Granulator - Fluidized Bed Granulator - Rotating Shape Granulator - Mechanical Agitator Granulator - five *Tablet Machines - Single Punch Tablet Press-simplest machine for tablet manufacturing that produces about 60-85 tablets/min. - Rotary Tablet Press-mechanical device that has several tooling stations which rotates to compress granules/powder mixture into tablets of uniform size, shape (depending on the punch design) and uniform weight. Quality Control equipment: * Disintegration Equipment - used to test how a drug in pellet form will disintegrate in solution. * USP Dissolution Tester - evaluates the rate and extent that a compound forms a solution under carefully controlled conditions. * Tablet Hardness Tester - applied to measure the breaking point of a tablet. * Tablet Thickness Tester - instrument that measures the thickness of tablets or in millimeters. * Tablet Friability Tester - measure the difference between the weight of the sample before and after the process in order to check the physical strength of uncoated tablets. Coating and Polishing Machines (for Coated Tablets): * Standard Coating Pan-tool used to coat a tablet with an aqueous or organic film. * Perforated Pan-equipment based on a film coating for tablets and production of pellets. * Fluidized Bed-used to reduce the moisture content in raw ingredients like powder and granules. * Air Suspension Coating System-can successfully coat small particles, pellets and tablets irrespective of size or shape with a wide variety of coating materials. Packaging Machines: * Blister Packaging Machines- can be used with diverse feed systems to create packaging solutions for unique product requirements. * Strip Packing Machine-designed to package capsules, caplets, tablets and soft gel into foil strips. * Aluminum Foil Packaging Machine-used to make a push-through closure called lid film or blister film.

Answer 8

• Compressed tablets account for a considerable part of tablets used in clinical settings to give systemic delivery of therapeutic drugs, either uncoated (ie., in their most basic form) or coated. These tablets are designed to disintegrate quickly in the stomach juice after consumption, allowing for fast drug release and, eventually, systemic absorption of the dose form. • Sugar-Coated Tablets - These are compressed tablets coated with a concentrated sugar solution to enhance patient compliance, boost visual appeal, conceal undesirable tastes or odors, Increase stability, and/or change therapeutic agent release (s). • Film-coated tablets are normal tablets coated with a thin coating of a skin-like polymer (e.g, hydroxypropyl methylcellulose, hydroxypropyl cellulose) or a polymer combination (eg, Eudragit E100). The film is generally colored and has the same general qualities as sugar coating, but it is more durable, less bulky, and takes less time to apply. The coating's composition is intended to shatter and reveal the core tablet at the desired place in the gastrointestinal system. • Effervescent tablets often contain organic acids (such as tartaric or citric acid) and sodium bicarbonate. In the presence of water, they swiftly react by producing carbon dioxide, which acts as a disintegrator to generate either a drug suspension or an aqueous solution. Granular effervescent salts (organic acid and bicarbonate) are compressed with the therapeutic ingredients to make these tablets. • Enteric-coated tablets are delayed-release pills that are compressed. They are covered with polymeric compounds that resist solubility in gastric fluid but breakdown and enable medication dissolution and absorption in the intestine (such as cellulose acetate phthalate/cellulose acetate butyrate; hydroxypropylmethylcellulose succinate; and methacrylic acid copolymers). •™Chewable pills are large tablets that are difficult to swallow and must therefore be chewed within the buccal cavity before swallowing. They are notably beneficial for administering big tablets to children and adults who have trouble swallowing traditional tablets or antacid formulations in which the tablet size is generally large and the tablet's neutralization efficiency is related to particle size within the stomach. •™Buccal and sublingual tablets are tiny, flat, oval tablets designed to be absorbed in the buccal pouch (buccal tablets) or beneath the tongue (sublingual tablets) for systemic absorption through the oral mucosa. These tablets are used to either achieve quick absorption into the systemic circulation, such as glyceryl trinitrate sublingual tablets, or to permit oral absorption of medications that are damaged by gastric juice and/or are poorly absorbed from the gastrointestinal tract.

Answer 9

1. type of fluid 2. mixing equipment 3. mixing operations

Answer 10

Suspensions

Answer 11

Step 1: Raw Material Selection - identifying the Solvents and the Solutes. Step 2: Liquid Oral Continuous Phase - solvents/ excipients are continuously added & mixed = aqueous solution. Step 3: Preparation of Dispersed Phase - certain drug added in order to increase solubility of liquid formulation. Step 4: Solution Finished Product Preparation - dissolving the solutes in solvent. Step 5: Packaging and Labelling - solution is being filled through a filling machine product, labelled, secondary packaging ready for distribution.

Answer 12

Hard Gelatin Capsules

Answer 13

Soft Gelatin Capsules

Answer 14

Step 1: Preparation of the gelatin solution (dipping solution) concentrated solution of gelatin is prepared by dissolving the gelatin in demineralized water which has been heated to 60–70°C in jacketed pressure vessels. 30 – 40% w/w of gelatin and is highly viscous, which causes bubbles as a result of air entrapment. To remove the air bubbles, a vacuum is applied to the solution. Presence of these bubbles in the final solution would yield capsules of inconsistent weight and would also become problematic during capsule filling and upon storage. Step 2: Dip-coating the gelatin solution on to metal pins (moulds) - by dipping pairs (body and cap) of standardized steel pins arranged in rows on metal bars into an aqueous gelatin solution (25 – 30% w/w) maintained at about 50°C in a jacketed heating pan. Moulds are below the gelling temperature; the gelatin begins to form a thin gelatin layer or film on the moulds. Step 3: Rotation of the dip-coated pins - the bar containing the pins is removed and rotated several times to evenly distribute the solution around the pins, correct gelatin distribution being critical to uniform and precise capsule wall thickness and dome strength. Step 4: Drying of the gelatin-coated pins - a blast of cool air is used to set the gelatin on the mould, the gelatin is dried, and the pins are then passed through several drying stages to achieve the target moisture content. Step 5: Stripping and trimming - capsule is stripped off the mould and trimmed to the proper length. Step 6: Joining of the trimmed capsule shell - the two halves (the cap and body) are joined to the pre-closed position using a pre lock mechanism; printing is done if needed before packing in cartons for shipping. Step 7: Printing - capsule shells can be printed to improve identification, using 1 or 2 colours, containing product name or code number, manufacturer’s name or logo and dosage details. It reduces the risk of product confusion by the numerous handlers and users of the product including manufacturers, pharmacists, nurses, doctors, caregivers, and patients.

Answer 15

1. Dipping - Pairs of the stainless steel pins are dipped into the dipping solution to simultaneously form the caps and bodies. The dipping solution is maintained at a temperature of 50°C in a heated, jacketed dipping pan. 2. Spinning - The pins are rotated to distribute the gelatin over the pins uniformly and to avoid the formation of a bead at the capsule ends. 3. Drying - The gelatin is dried by a blast of cool air to form a hard shells. The pins are moved through a series of air drying kilns to remove water. 4. Stripping - A series of bronze jaws strip the cap and body portions of the capsules from the pins. 5. Trimming and joining - The stripped cap and body portions are trimmed to the required length by stationary knives. After trimming to the right length, the cap and the body portion are joined and ejected from the machine.

Answer 16

ACTIVE INGREDIENTS: influence capsule size and the nature and amount to be used in the formulation, tend to make up a high percentage of the contents of a capsule as compared to tablets, smaller the size the larger surface area and greater rate of dissolution. FILLERS (DILUENTS): increase the bulk of the formulation. Ex. starch, lactose & dicalcium phosphate. Improve flow properties & compatibility. GLIDANTS: improve the fluidity of powders. Ex. colloidal silica, cornstarch, talc & magnesium stearate. LUBRICANTS: ease the ejection of plugs, reduce filming on piston & adhesion of powders to metal surface. Reduce the friction between sticking surfaces in contact w/ powder. Ex. magnesium stearate and stearic acid. DISINTEGRANTS: superior swelling or moisture-absorbing properties are generally used as disintegrants. “super disintegrants”. E.g. croscarmellose sodium, sodium starch glycolate and crospovidone. SURFACTANTS: increase the wetting of the powder mass & enhance drug dissolution. E.g. sodium lauryl sulphate & sodium docusate. Concentration range: 0.1-0.5%. HYDROPHILIC AGENTS: improve the wettability of poorly soluble drug present in hard gelatin capsules. hexobarbital (hard gelatin capsule) could be enhanced if treated w/ methyl cellulose or hydroxyl ethyl cellulose.

Answer 17

1. Automatic Capsule Filling Machine –capable of accurately filling powder, pellets, and grains into a wide range of gelatin capsule sizes, aid in slug production, vacuum cleaning station is available for segment cleaning, frame is made of stainless steel 316/304,. 2. Semi-Automatic Capsule Filler –typically preferred for precision manufacturing requirements. Higher level automation & greater filling weight accuracy, generate 25000 and 45000 capsules/hour 3. Hand Capsule Filling Machine –tabletop machine suitable for pilot and production batch requirements, easily dismantle for cleaning operations, calls for precision machined components & assembled w/ highly skilled personnel. 4. Softgel Encapsulation Machine - fills the gelatin shells with semi-liquid or liquid substances, responsible for the encapsulation of API. 5. Manual Capsule Filling Machine – work with powders, pellets & granules. It can be totally disassembled, made of stainless 304, appropriate for long operations, manufacture 6000 capsules/hour

Answer 18

SOFT GELATIN: ROBITUSSIN, OMEPRAZOLE, FOLIC ACID, CALCITROL, ADVIL HARD GELATIN: LOPERAMIDE, RETINOL, LANSOPRAZOLE, UROSODEOXY CHOLIC ACID, VITAMIN B2 B6 B12, FERROUS SALT + FOLLIC ACID