Reporting: Solution-tablets

Question 1

Classifications of Solutions:

Answer 1

Oral
Optic
Opthalmic
Topical

Question 2

aqueous solutions containing sugar

Answer 2

Syrup

Question 3

sweetened hydroalcoholic solutions (H2O + C2H6O)

Answer 3

Elixirs

Question 4

solutions of
- aromatic materials (if the alcoholic)
- aromatic water (if the solvent is aqueous)

Answer 4

Spirits

Question 5

“Fluid extracts”; solutions prepared by extracting active constituents from crude drugs.

Answer 5

Tinctures

Question 6

Characteristics of Solutions:

Answer 6

advantage:
easy to swallow (pediatric, geriatric)
fast absorption rate
flexible dosing

disadvantage:
less stable < solid dosage forms
color change
precipitation
microbial growth
chemical gas formation

Question 7

Solution: Steps/Processes

Answer 7

Step 1: Raw Material Selection
Solutes
- Active ingredients (solutes; organic medicinal agents, weak acids/weak bases)
- Excipients (stabilizers, coloring/flavoring, preservatives)

Solvents
- match specific solute (solubility, clarity, palatability, toxicity, viscosity, color, economic feasibility)
ex. H20/Aromatic H2O, OH, glycerin

Question 8

Methods: Simple Solution

Answer 8

1. dissolve solute in suitable solvent
2. mix to dissolve
3. add sufficient solvent to bring up solution to proper volume
4. All components are put & mix to form solution.
5. To enhance dissolution: heat might be applied, reduce particle size, vigorous mixing.
6. To avoid loss by evaporation/degradation of volatile components by heat: + at the end process after cooling

other ingredients: Stabilizer/solubilizer
- calcium hydroxide topical solution USP (Lime H2O)
- sodium phosphate oral solution USP
- strong iodine solution USP

Question 9

Methods: Solution by chemical reaction

Answer 9

Preparation (reacting 2 or more solutes + suitable solvent)
ex. Magnesium citrate (magnesium carbonate w/citric acid + flavoring, sweetening agents, filtering talc & carbonating it by potassium or sodium bicarbonate)

Question 10

Methods: Solution by Extraction
Methods: Solution by Distillation

Answer 10

Extraction (vegetable/animal origin) w/ suitable solvent. Classified as extractives.

Distilling the volatile principles from a drug inside a copper wire cage which allows the free passage of vapors and
boiling water.

Question 11

Machines & Equipements (SOLUTIONS)

Answer 11

1. Mixing & storage tanks - hold & mix liquids, compressed gasses/mediums used for short/long-term storage (heat/cold).
2. Filter press - separates liquid & solids remove impurities, suspend solids by pressure filtration.
3. Homogenizers - make stable & clinically effective (handle particle size under high pressures, sheer turbulence, acceleration, and impact)
4. Liquid Filling Machine - fill bottles, vials, ampules, etc. w/ predetermined quantity of liquids
   Distillation Unit - separate 2 or more mixed liquids by heating
5. Deionizer - removal of ions from solution (ion exchange process)
6. Labelling Machine - dispense, apply/print labels to various items
7. Agitators - mixing, shaking, vibrating fluids
8. Manufacturing/Proces Vessel - container w/ controls to complete sub-process as part of overall process.
9. Leak test apparatus - test packing process & leakages.
10. Bottle washing machine - automatically washes bottles.
11. Turn table/unscrambler - revolvable platform, makes bottles go through filling process.
12. Cap sealing machine - leak-proof seal is applied to the opening of the container

Question 12

SOLUTION examples:

Answer 12

Syrups
• Ambroxol (Ambrolex) Syrup
• Ascorbi Acid (Ceelin) Syrup
• Carbocisteine (Ceascol) Syrup
• Lagundi Ascof Syrup
• Paracetamol (Tempra) Syrup

Spirits
• Aromatic ammonia spirit
• Camphor spirit
• Ethyl nitrate spirit

Elixir
• Chlorpheniramine maleate (USP) (Antihistaminic)
• Diphenydramine HCI (Antihistaminic)

Otic Solutions
• Ciprodex (ciprofloxacin/dexamethasone)
• Vosol HC (acetic acid/hydrocortisone)
• Cortisporin Otic (hydrocortisone)

Ophthalmic Solutions
• Ketorolac
• Tromethamine
• Diclofenac
• Flurbiprofen

Topical Solutions
• Aluminum acetate solution
• Calcium hydroxide topical solution
• Povidone lodine Solution

Question 13

a heterogeneous system consisting of 2 phases; internal phase is dispersed uniformly throughout the external phase.

1. internal phase - particulate matter (insoluble but dispersed uniformly throughout the continuous phase) w/ aid of single or combination of suspending agent.
2. External phase (suspending medium) is generally aqueous in some instance, may be an organic or oily liquid for non-oral use

Answer 13

Suspension

Question 14

CHARACTERISTICS of SUSPENSION:

Answer 14

• heterogeneous systems (solid particles are spread throughout the liquid without dissolving in it)
• Improve chemical stability of certain drug and has a higher bioavailability than other dosage forms.
• Finely divided particle of solid are dispersed in liquid.
• It is unstable; particles of a suspension settle down after some time.
• Available for oral, parenteral, external use.
• Available in capsule, compressed tablet, coated tablet, and syrup

Question 15

Process SUSPENSION:

Answer 15

1. particle size is reduced to a desired size w/ mill or other equipments.
2. Insoluble materials are levigated or grinded to a smooth paste w/ a vehicle containing the wetting agent.
3. All soluble ingredients are dissolved in same portion of the vehicle and added to the smooth paste to get slurry.
   * Small scale preparation, the slurry is then transferred to a graduated cylinder & mortar is rinsed with successive portion of vehicle.
   * Industrial scale, then slurry is transferred to a colloid mill or a disperser or any other equipment to completely wet the particles.
4. Then a deflocculated suspension is obtained.
5. Decide whether the solids are: Suspended in a structured vehicle, Flocculated, Deflocculated and then suspended
6. Add vehicle containing the suspending agent or flocculating agent.
7. Make up the dispersion to the final volume. Thus suspension is prepared.

Formulation Flow:
Finely divided particles -> Particles are added in dispersion medium -> Wetting agent is added -> Deflocculated suspension

Question 16

Methods: Precipitation

Answer 16

Three precipitation methods used:
1. Organic solvent precipitation - H2O insoluble drugs can be precipitated by dissolving them in water- miscible organic solvent and then + organic phase to distilled water under standard conditions.
Eg. Organic solvents used are ethanol, methanol, propylene glycol and polyethylene glycol.
2. Precipitation by pH - changing the pH of medium is more readily accomplished and does not present the same difficulties associated with organic solvent precipitation. Applicable only to those drugs in which solubility is dependent on pH value.
Eg. Estradiol Suspension and Insulin Suspension.
3. Double Decomposition - involves simple chemistry,
Eg While Lotion (NF XIII).

Question 17

Method: Dispersion

Answer 17

Vehicle must be formulated so that solid phase is easily wetted & dispersed.
Use of surfactant is desirable to ensure uniform wetting of hydrophobic solid.
Use of suspending agent such as synthetic polymer, natural gums and others may be indicated depending upon specific application.
Actual dispersing of solids may/may not cause particle size reduction. If particle size reduction occurs, the particles obtained may have different solubilities and this may lead to super saturation of the system.

Question 18

Method: Use of Controlled Flocculation

Answer 18

Controlled flocculation of particles is obtained by adding flocculating agents, which are: Electrolytes, Surfactants, Polymers

Question 19

GENERATING NEW DESIGNS FOR DRUG FORMULATION:

Answer 19

1. Nanosuspension - it can increase the dissolution velocity as well as the saturation solubility.
2. Taste masked pharmaceutical suspensions - the coating acts as a physical barrier to the drug particles, thereby minimizing interaction between the drug and taste buds.
3. Sustained release suspensions - allows delivery of a specific drug at a programmed rate that leads to drug delivery for a prolonged period of time

Question 20

Machines/Equipment SUSPENSION:

Answer 20

1. Mortar and pestle - hardwood, metal, ceramic, granite. Pestle - blunt, club-shaped.
2. Agitators/Mechanical Stirrers (propellers; produce axial movements; turbines produce radial and tangential movements) mounted on shafts.
   • Low viscosity (propeller type)
   • Higher viscosity (turbine type)
   Degree of agitation is controlled by the rotational speed of impeller, by the patterns of the liquid flow and the resultant efficiency of mixing are controlled by the type of impeller, its position in the container, the presence of baffles, and the general shape of the container.
   Advantages: Used for small-scale production & laboratory purpose.
   Disadvantages: Continuous shaking tends to break up the phase to be dispersed & the dispersion medium, = impairs the ease of suspension.
3. Colloid Mill - passage of the mixed phases of a suspension between a stator and a high speed rotor revolving at speeds of 2000-18,000 rpm. Clearance between the rotor and the stator is adjustable, usually from 0.001 inch upward. The suspension mixture, while passing between the rotor and the stator, is subjected to a tremendous shearing action which effects a fine dispersion of uniform size. Shearing forces applied in the colloid mill usaty rates the temperature within the suspension. Hence, a coolant is used to absorb the excess heat.
   Advantage: Very high shearing force can be generated, very fine particles can be prepared, particularly useful in preparing suspensions containing poorly wetted solids, useful for the preparation of relatively viscous emulsions
   Disadvantages:
   No wide applications in solids, Wear of the rotating plates, no fine grinding, consume energy
4. Homogenizer - Impeller type of equipment frequently produces satefactory amulsion however, for further reduction in particle size, homogenizers may be employed
   Homogenizers may be used in one of two ways:
   a. The ingredients in the suspension are mixed and then passed through the homogenizer to produce the final product.
   a. Corse suspension is prepared in some other way and then passed through a homogenizer for the purpose of decreasing the particle size and obtaining a greater degree of uniformity and stability.
5. Piston Homogenizer - most powerful device for producing emulsions and suspensions It uses high power positive displacement piston type pump to produce pressure of 3000-10,000 palg and then force the premixed product + through a specially designed restricling wall where a extremely high shear forces are exerted Here turbulence and high shear are the major parameters in size reduction it having continuous Capabilities of 2500L/hr at 15hp - 50,000L/hr at 150hp
   Limitations: They cannot handle the product feed above 200 cps High maintenance cost and downtime.
6. Ultrasonic Devices - preparation of emulsions by the use of ultrasonic vibrations abo is possible. An oscillator of high frequency (100 to 500 kHz) is connected to two electrodes between which placed a piezoelectric quartz plate. The quartz plate and electrodes are immersed in an oil bath and, when the oscillator is operating, high-frequency waves flow through the fluid Emulsification is accomplished by simply immersing a tube containing the emulsion ingredients into this oil bath.
   Advantages:
   Used for low viscosity and extremely low particle size.
   Disadvantages
   Only in laboratory scale it is possible Large scale production is not possible.
7. Size Reduction Equipment
   • Triple roll mill: Disperse small lightly bound agglomerates and hard discrete. Particles are subjected to high shear, mechanical crushing.
   • Ball Mill: used for size reduction fine solid discrete particles or for deagglomeration of very tightly bound agglomerates. Machine consists of cylindrical drum into which a charge of heavy spherical balls usually metal or ceramic is loaded along with the components of the dispersion

Question 21

SUSPENSION examples:

Answer 21

1. Antacid oral suspension
   (Eg. aluminium hydroxide, magnesium carbonate, magnesium trisilicate, magnesium hydroxide, calcium carbonate, and sodium bicarbonate).
2. Antibacterials oral suspension (Antibiotics) (Eg. Ciprofloxacin and Erythromycin estolate).
3. Dry powders for oral suspension
   (Eg. Zithromax Powder)
4. Analgesic oral suspension
   (Eg. Ibuprofen, paracetamol)
5. Anthelmintic oral suspension
   (Eg. Pyrantel pamoate and Thiabendazole)
6. Anticonvulsant oral suspension
   (Eg. Phenytoin)
7. Antifungal oral suspension
   (Eg. itraconazole, fluconazole, ketoconazole and terbinafine).
8. External applied suspension
   (Eg. Calamine lotion)
9. Parenteral suspension
   (Eg. Procaine penicillin G, Insulin Zinc Suspension)

Question 22

Dry, solid substance, finely divided drugs with/without excipient that is intended for internal/external use.
Finely divided state (10nm-1000 μm)
Obtained by crushing, grinding, or comminuting.”

Answer 22

Powders

Question 23

Methods in Powders:

Answer 23

1. Trituration - Process involves direct rubbing or grinding of hard powder in a mortar and pestle. The trituration method is used for both pulverization and mixing.
2. Spatulation - a powder spatula is used in this method. Powders are mixed on a pill tile (ointment slab) or in a mortar. This method is adequate for mixing small amounts of powders and combinations of powders having the same densities.
3. Sifting - helpful for powders that resist mixing by trituration. Very light powders, such as magnesium oxide and charcoal, can be completely mixed by shaking them through a sieve.
4. Tumbling - mixing powders by shaking or rotating them in a closed container. This method is used when two or more powders have considerable density differences. This mode of mixing does not yield particle size reduction and compaction.

Question 24

POWDERS CAN BE CLASSIFIED AS:
1 Based on use.
2 Based on particle size
3. Based on dispensing

Answer 24

CLASSIFICATION BASED ON USE:
a. Pharmaceutical powders for internal use - A preparation that consist of solid, loose dry particles that can be taken orally, can be administered through the nose as snuffs or blown into the body.
b. Pharmaceutical powders for external use - Known as powders for cutaneous application thatcontain one or more active substances, with or without excipients.

CLASSIFICATION BASED ON PRTICLE SIZE
a. Very coarse powder: No. 8 sieve
b. Coarse powder: No. 20 sieve
c. Moderately coarse: No. 40 sieve
d. Fine: No. 60 sieve
e. Very fine: No. 80 sieve

CLASSIFICATION BASED ON DISPENSING:
a. Bulk powders - mixture of all the materials packed into a properly designed bulk containers, such as a tight, wide-mouthed glass or plastic bottle.
The dose of bulk powders can be affected by many factors, including: measuring device (spoon), storage humidity, degree of settling, patient factors.
b. Divided powders - are single doses of powdered drug mixtures individually enclosed in paper, plastic laminates, or metallic foil wrappers or packets

Question 25

New Design for Drug Formulation:

Answer 25

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.

Question 26

Equipments POWDERS:

Answer 26

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.

Question 27

POWDER examples:

Answer 27

• 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).

Question 28

Most commonly prescribed dosage form for getting drugs into the body. They are: compact drugs, thus easier to carry, solid dose pharmaceutical preparation containing drug substances usually prepared w/ the aid of suitable pharmaceutical excipients. They may vary in size, shape, weight, hardness, thickness, disintegration, and dissolution characteristics and in other aspects, depending on their intended use and method of manufacture.

Answer 28

Tablets

Question 29

Characteristics of the tablets:

Answer 29

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.

Question 30

Process in TABLETS:

Answer 30

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.

Question 31

Methods of Tablets production:

Answer 31

• 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.

Question 32

Materials/Equipment TABLETS:

Answer 32

• 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.

Question 33

Tablet examples:

Answer 33

• 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.

Question 34

refers to a single phase system, or clear homogenous preparation consisting of one or more APIs dissolved in a suitable aqueous or non-aqueous vehicle.

may be prepared from any combination of solid, liquid, and gas [the three states of matter]

“liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents”.

Answer 34

Solutions

Question 35

The most important physical factors that influence the solubility of ingredients in solutions:

Answer 35

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

Question 36

Grinded solid drug

Answer 36

Suspensions

Question 37

Oils solubilized drug

Answer 37

Emulsions

Question 38

Processes/Steps in
Manufacturing Solutions:

Answer 38

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.

Question 39

solid dosage forms in which the drug substance in enclosed within either a hard or soft soluble shell,
usually formed from gelatin.

Answer 39

Capsules

Question 40

“dry-filled capsules” or two-piece capsules, consist of two parts: capsule body (longer part), capsule cap (the shorter part). The drug substance is placed in the
body and the caps are slided over it, hence
enclosing the drug substance. Each of a different
color. This form of capsule holds dry ingredients in
powder form.
Once ingested, the hard capsules disintegrate
within 3 mins and quickly release the drug
inside, hygroscopic and contain a higher water content than the soft capsules at around 12-15%.

Answer 40

Hard Gelatin Capsules

Question 41

“softgels”, single piece of gelatin available in round, oval and tube-like shapes, rather than two halves attached together. For administration of liquid medicaments for solutions not based on water, as this would dissolve the gelatin, but for oil-based solutions.
Gelatin is hygroscopic in nature, and the
gels contain between 5-14% water.

Answer 41

Soft Gelatin Capsules

Question 42

Process in CAPSULE formulation:

Answer 42

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.

Question 43

Method of Production in CAPSULES:

Answer 43

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.

Question 44

Generating New Designs for Gelatin Capsule Formulation:

Answer 44

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.

Question 45

Machines/equipment for Capsules:

Answer 45

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

Question 46

Pharmaceutical Example of Capsule:

Answer 46

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