Solid Dosage Forms (Tablet)

Talc powder

1-5% Is a poor lubricant but is an exccelent anti-adherent property. It is a reasonably good glidant

Water soluble lubricants

1-5% Carbowax 4000, carbowax 8000, and somdium lauryl sulfate

Stearic acid

1-5% Good lubricant but poor anti-adherent and lacks glidant property Similar to magnesium stearate

Dry Corn starch

5-10% Is an excellent glidant and anti-adherent but poor lubricant You will see this combined with Magnesium stearate

Multiple Compressed Tablets

A compressed tablets that are prepared by subjection to more than a single compressed cycle. Therefore, there are two or more layers which could possible have different Active Ingredients. The separation is intended to minimize the interaction of each Ex. Meclizine, Allegra D

Motting

A phenomenon of uneven distribution of coloring agent in particular tablets yeilding darker spots of the color on a tablet

Diluents or fillers

Add to the formulation to increase the bulk of a tablet to a practical and convenient size Important for low dose drugs

Vaginal Tablets

Are ovoid or pear shaped conventional compressed tablets intended for insertion into vagina. These tablets usually contain -antiseptic -Astringent -Steroid -Antifungal agents Usually inserted by means of a plastic tube inserter. Ex. Vagifem

pH's

Coated tablets are sensitive and dissolve at different ____?

Film Coated tablet

Compressed tablets coated with colored or uncolored thin film of water soluble polymeric material which disintegrates rapidly in the GI tract. it is also good tasting and replaced sugar coated tablets due to low cost. Erythromycin is one of the most bitter tasting so they do film coated preparations to counteract this.

Chewable Tablets

Compressed tablets designed to be chewed before swallowing. Is an important dosage form for pediatric patients. Usually made with flavoring agents to allow the patient to chew the tablet. Ex. Amoxcillin, Augmentin, Singulair

Sugar Coated Tablet

Compressed tablets that are coated with several successive thin layers of colored or colorless sucrose solutions. You are not likely to find to many products prepared by this technique due to high cost.

Effervescent Tablets

Compressed tablets which effervesces when in contact with water and liberates the drug Dosage form that involves an acid based reaction to release carbon dioxide. The release of carbon dioxide masks bitter tasting API's. Ex. Alka-seltzer

Tablet Disintegration test

Determines the time required for a tablet to disintegrate, when immersed in some test fluid; generally simulated GI fluid

Without liquids

Dry granulation method

Photosenstive

Dyes and lakes are ________ which is affected by the drug, excipients added, and method of manufacturing.

Magnesium Stearate < 1%

Excellent lubricant but poor anti-adherent and glidant. Should not be used more > than 1% or may cause dissolution problems. Poorly soluble substance

Anti-Adherents

Excipient that functions to prevent tablet granules from sticking to faces of punches and dye wall

Disintegrant

Facilitates the tablets ability to break up following administration.

poor compressibility

High porosity causes what?

Surface active agent

If the drug is hydrophobic what kind of excipient do you need?

Drug Content Uniformity

Is required for ALL dosage forms This test is designed to establish drug homogeneity in the tablet of each batch of products

Laurly Sulfate

Is the commonly used WATER SOLUBLE lubricant that also functions as a wetting agent

Direct compression/ Dry granulation method

It involves powder blend of API and IAI and this is compressed - Milling (reducing the particle size) of the API and IAI through sieving - Mix API and IAI - Compress into tab

Granule

It is a small particle that is composed of powders which consist of active and inactive ingredients.

Enteric Coated Tablet

It is a type of suspended release tablet designed to release some portion of API in the GI tract. The coating material is usually pH sensitive and dissolves in basic solution. So it does not dissolve in the stomach instead it dissolves in the intestinal tract. Ex. Aspirin

Dry excipients

Lakes are blended with dry or wet excipients.

Primojel or Explotab

Low substituted carboxymethyl starch. It is used at 1-8% (optimum is 4%)

Glident

Materials that improve the flow characteristics of the granules. Act by reducing the inter-particulate friction When used in right amount, they serve to assure smooth and uniform flow of granules.

Various Starches (disintegrants)

Mode of action is the water uptake through the pores of tablets, due to capillary action, which results in tablet expansion followed by disintegration

130mg

No more than 2 tablet can differ from the mean by than +- 10%. NO tabelt can differ from the mean by more than +-15

>324mg

No more than 2 tablet can differ from the mean by than +- 5%. NO tablet can differ from the mean by more than +-10mg.

130-324mg

No more than 2 tablet can differ from the mean by than +- 7.5%. NO tablet can differ from the mean by more than +-15

Wet granulation

Powder API is mixed with diluents, disintegrant, colorant, and binding agent (solution) Mixture is passed through a sieve and granules are prepared Granules are dried, mixed with lubricant and compressed into tablets

Rapid dissolution

Rapid disintegration of a tablet is likely to result in rapid _________ but it is not guaranteed.

Dissolution Test

Required by FDA A process by which a solid drug dissolves in the surrounding fluid.

*Weight Variation*

Required by the FDA Twenty tablets are weight individually Determine the mean weight and Std Dev USP and NF provide the specification with regards to how many tablets can deviate from the std dev.

Inter-granular

Suggest the presence of disintegrant inside the granules

Extra-granular

Suggest the presence of disintegrating agent between the granules

1. Disintegrating agents 2. Coloring agents 3. Flavoring agents 4. Sweetening agent 5. Surface active agent 6. Preservatives

Tablet Excipients are classified into 2 groups. Group 2 helps to lend additional desirable physical characteristics to the finished tablet. Group 2 includes?

Tablet Hardness Test

Tablet must be sufficienty strong and resistant to abrasion to withstand handling during manufacturing, packaging, and shipping In addition, it should withstand physical abuse in pharmacy by staff and at home by the patient

Diluents Binders Lubricants

Tablets Excipients are classified into 2 groups. Group 1 imparts satisfactory compression characteristics and flow priorities. What is Group 1 is composed of what?

Oral Disintegrating Tablet

Tablets designed to disintegrate in the oral cavity

Friability Test (Resistance to abrasion)

Test measures the weight loss in tablets upon subjecting certain number of tablets to agitation under standard conditions.

Tablet Hardness Test

Test performed to measure the force required to fracture a tablet.

Compressibility

The ability of a powder particle to compress to make a tablet

Mositure content

The amount of intrinsic moisture in a powder.

Simply sugar or polymer

The different colors of coated tablets are sometimes made of?

Migration

The speed in which we dry colorants on the surface of the tablet, determines if the colorant will be uniformly distributed.

Agglomerates

The surface phenomenon of clumping powder particles together.

Sublingual Tablets

These are compressed tablets, which are usually flat or oval in shape, and intended to provide systemic action by placing them beneath the tongue. Disintegration is important

Buccal Tablets

These are compressed tablets, which are usually flat or oval in shape, and intended to provide systemic action by placing them between the cheek and gums. Disintegration is important.

Lozenges and Troches

These are disk shaped solid dosage form made of therapeutic agents and flavoring agents intended for slow dissolution in the mouth for continuous local application of the drug to the mucous membrane of the oral cavity. Ex. cough drops

Sustained Action Tablets

These tablets provide an initial sufficient amount of drug to cause a rapid onset of the desired therapeutic response and an additional amount of that maintains the response at the initial level for a longer period than obtained after administration of conventional single dose of that drug.

Lubricants

This excipient acts between surfaces in relative motios to prevent friction and wear Helps granules to slip and slide to form a compact In the dye wall of a tablet press Inadequate amount of this excipient is seen by screeching sound and scratch marks on the edge of the tablet

Binding agents

This excipient is part of group 1 and is incorporated in the formulation to impart cohesive property to the powder mixture (granules). The cohesiveness ensures that the tablet will remain intact after compression and until pt uses it.

Tablet

USP/NF definition: a compressed solid dosage form containing medicinal substances with or without suitable excipents.

Noyes-whitney equation

Various factor influence the dissolution of a drug including surface area, higher soluble concentration gradient.

With liquids

Wet granulation method

Compressed tablet (single compressed tablet) Multiple Compressed Tablet Enteric Coated Tablet Oral Disintegrating Tablet Sugar Coated Tablet Film-Coated Tablet Effervescent Tablet Chewable Tablet Sustained-Action Tablet (Modified release dosage)

What are all the class of compressed tablets which are delivered into the GI tract

- Dry acacia - Acacia mucilage (binding and emulsifying agent 2-5%) - Dry tragacanth - Tragacanth mucilage (1 or 3% aqueous) - Warm gelatin (1-4 %) -Starch Paste - Polyvinyl Pyrrolidone (PVP) - Methyl Cellulose -Ethyl cellulose - Hydroxypropyl methyl cellulose

What are commonly used binders

FD&C #40 FD&C #5 and #6 FD&C blue #1 and #2 FD&C green #3

What are commonly used colorants?

Methyl Cellulose Ethyl Cellulose Hydroxyproyl cellulose

What are some cellulose derivative binding agents

Lactose Spray dried lactose Microcrystalline cellulose Mannitol *Dry* starch Powder sugar

What are some commonly used diluents?

Various starches Primojel or Explotab Pre-gelatinized starch Microcyrstalline cellulose

What are some commonly used disintegrants?

Digoxin Levothyroxine Captopril

What are some examples of low dose drug that require diluents?

Aspirin Alprazolam Ambien Metoprolol Tartrate Diovan Ibuprofen Tylenol are a few

What are some examples of single compression tablets?

- Its expensive - Moisture sensitive drugs might need non-aqueous binder - Migration of water soluble dyes might cause mottling - Heat sensitive drugs may be difficult to formulate

What are some limitations to using wet granulation method

Cone blender powder Vertical Mixer V shaped blender

What are some mixing machines for tablet dosage forms

Vaginal Tablets Implantation Tablets Diagnostic tablets (diagnostic test)

What are some other uses for tablets and tablet types?

Flow Angle of repose Bulk Density True Density Cohesiveness Compressibility Particle Size and shape

What are some powder properties that make it difficult to make a formulation for a tablet.

Buccal and Sublingual Tablets Lozenges and Troches

What are some tablets that are used in the Oral Cavity

Carr's index Hausner ratio

What are some test performed to determine a particles compressibility?

Basket method Paddle method

What are the 2 USP apparatus to test dissolution.

Active ingredient Inactive Ingredient

What are the 2 components of tablet dosage form

Granule Properties Granule Compression Compressed Tablet Tablet Ejection

What are the 4 components of compression?

- Economical - Suitable for heat and moisture sensitive drugs

What are the advantages to direct compression/dry granulation method?

Ease administering accurate dose of a drug Easy to transport and store More chemically stable compared to liquid DF Cheaper to make Popular

What are the advantages to tablet dosage form

- Provides the best uniform distribution and makes it ideal for *low dose drugs* - Provides good cohesiveness and compressibilty to the powder because of liquid binder - There is minimum segregation of the powder (the api and iai are all formed into the granule)

What are the advantages to using the wet granulation method

Excess Heat Uneven mixing High concentration of colorant

What are the causes of mottling?

Difficulty in swallowing tablets for geriatric and pediatric patients. Developing a formulation is challenging especially for hydrophobic drugs

What are the disadvantages to tablet dosage form?

- Not good for low dose drugs - May end up with non-uniformity - Drugs end up with high dose, high bulk volume (low bulk density) poor compressibility and poor flow.

What are the disadvantages to the direct compression/dry granulation method.

*Weight Variation* *Drug Content Uniformity* Tablet disintegration *Drug dissolution* Tablet hardness Friabilty

What are the evaluation methods performed on tablets?

Compatability with active ingredients Physically stable Should be physiologically inert Low cost

What are the fulfillment criteria for excipents

1. Mixing of the solid ingredients of the formulation (API and IAI and disintegrating agent) 2. Mixing of a liquid, when applicable, and preparation of wet powder mass (binding agents) 3. Passing the moist powder mass through a sieve (#10, 20, or 30) and prepare wet granules 4. Drying of moist granules (Heat) 5. Mixing of dried granules with other excipient (lubricants and portion of disintegrating agent) (Principles of solid-solid mixing) 6. Compression of granules into a tablet of suitable size shape and employing tablet die 7. Each batch of a product, generally consist of 100,000 to million tablets 8. Powders (drug as well as IAI) used in making a lot, weight in kg quantities

What are the important steps to making a tablet dosage form

Lubricants Glider Anti-Adherent

What are the three classifications of lubricants?

Uncoated Coated Scored

What are three ways tablets are available?

Dyes

What are water soluble colorants

Tablet Disintegration test

What exam is most important for oral disintegrating agent?

Lactose

What excipient will exhibit discoloration problems

- The powder properties - Dose of the drug (Small or large dose) - Available equipment -Practical and regulatory concerns (price)

What factors determine which tablet preparation method( wet/dry granulation) you should use?

Active ingredients and Excipients/additives/inactive ingredients/adjuvents

What is a tablet composed of?

Lakes

What is a water insoluble colorant formed by adsorption of water soluble dye on a hydrous oxide (usually aluminum hydroxide).

Adsorption

What is an issue colorants have with Active ingredients and inactive ingredients with photosensitivity.

0.8 - 1%

What is the acceptable index of abrasion % for the friability test?

85-115% with none to exceed 75-125% range

What is the desired range for the Drug content uniformity test?

B = 100( 1 - W/W0)

What is the formula for the friability test

Microcrystalline cellulose

What is the most common conventent diluent that is very compatible with all Active ingredients, is stable, and has no discoloration problems. Also acts as a disintegrant

0.05-0.1%

What is the recommended concentration of coloring agent?

Solid tablet --> disintegration-> dissolution.

What is the steps of a dissolution for a tablet in the GI tract?

1. Tablet enters GI tract 2. Tablet with pores and capillary allows aqueous fluids to enter tablet 3. Swelling or disintegrating agent will build the pressure inside the tablet and allow it to burst open.

What is the tablet disintegration process?

Scored tablets

What kind variation of a tablet make it easy for a patient to break apart.

Prior to granulation or during the lubrication step which is before the compression. Or at both step

When can disintegrating agent be added?

During the wet granulation method.

When is binding agent added in the formulation of tablets?

With binding agent solution

When is coloring agent incorporated?

Ethyl cellulose

Which cellulose binding agent is insoluble in water?

Hydroxypropyl methyl cellulose

Which cellulose binding agent is soluble in water, alcohol, chloroform, and methylene chloride

Mannitol Lactose Sorbitol Sucrose

Which diluents are sweet tasting and are commonly seen in chewable tablets

Dissolution

Which is more important for complete absorption to occur thus good bioavailability, disintegration or dissolution?

-Identifying different products -Identifying different strengths of the same product - Minimize the possible mix-up during manufacturing - Aesthetic and/or marketing value

Why are colorants incorporated into formulations?

- Improve the flow of granules -Reduce adhesion of powder material to punch and dyes during compression Easy release of the compressed tablet from the mold or dye

Why are lubricants incorporated into formulations?

It interacts with plastic material and loses its effectiveness of the drug by 50%.

Why is nitroglycerin only available in a glass container?

True

[T/F] A lot of Binding agents double as suspending agents

True

[T/F] Binding agents are more effective when used as mucilage compared to dry powder

False

[T/F] Colorants are more effective in producing the coloring effect in powder form than solution

True

[T/F] Drying granules slowly at low temperature and with continuous stirring can reduce migration of the color to surface and reduce mottling

True

[T/F] Frequently, it may be necessary to employ combination of two lubricants in a formulation

True

[T/F] Generally the faster the dissolution rate and more complete the drug dissolution, the faster and more complete is the drug more likely to be absorbed.

False

[T/F] Group 1 tablet excipients impart satisfactory compression characteristics and desirable physical characteristics to the tablet

False

[T/F] If a tablet disintegrates quickly it is guaranteed to dissolve quickly and subsequently be absorbed immediately as well.

True

[T/F] If you use the right inactive ingredient you can still use the wrong amount resulting in adverse effects.

True

[T/F] In general lubricants, whether water soluble or insoluble should be very fine particle size.

False

[T/F] Inactive ingredients are not limited to a single use.

False

[T/F] Most lubricants only posses one of the three attributes of glident, lubricant, and anti-adherent

False

[T/F] Multi film coating of lubricants cause no dissolution problem

True

[T/F] Since Lubricants function by forming a thin film around the granules, their effectiveness is related to the particle size

True

[T/F] Starch paste and Polyvinyl Pyrolidone (PVP) require preservatives

False

[T/F] The FDA does not have to approve all colorant s to be used in pharmaceutical formulations

True

[T/F] The effectiveness of many disintegrants is affected by there position (inter or extra granular) within the tablet

False

[T/F]Mucilage form does not require presence of preservatives

Cohesivenss

the ability of powder particle to stick together and remain intact

Starch Paste

(5%-10%) Effective bind