solid oral dosage forms

What molecular properties make poor absorption more likely according to Lipinski’s rule of 5?

Molecular weight <500, logP <5, <5 hydrogen bond donors and <10 hydrogen bond acceptors

Benefits of solid dosage forms

• contain correct quantity of AI

• Stable

• Easily portable

• Can be administered easily

Why is Lipinski’s rule of 5 important?

Drug development and formulation

What does the Biopharmaceutical Classification System (BCS) classify APIs based on?

Aqueous solubility and intestinal permeability.

What major factors govern the rate and extent of API absorption from immediate-release oral solid dosage forms?

Excipient composition, dissolution, solubility and intestinal permeability

What additional aspects are considered when applying the BCS to pharmaceutical products?

Dissolution of the pharmaceutical product and critical examination of its excipients.

Why does particle size matter in pharmaceutical formulation?

Dissolution rate, powder flow rate and powder packing type

How are active ingredients administered in powder dosage forms?

Orally, with or without excipients

How are oral powders usually administered?

In or with water

What must be considered when using multidose powder containers?

Powder measurement, dosing accuracy, ingredient toxicity and stability

What are the disadvantages of oral powder dosage forms?

They are bulky, inconvenient to use and provide little taste masking

What is an example of a specialised powder dosage form?

Effervescent powders

How can ingredient segregation in powders be avoided?

Granulation

What is granulation?

The process of forming larger multiparticulate entities called granules from primary powder particles

What is the particle size of granules according to the notes?

>1,000 micrometres; generally 0.2–4 mm

What are the benefits of granulation

Prevents component segregation and improves powder flow and compaction

How is wet granulation performed?

Dry primary powder particles are mixed with a granulating fluid

Which volatile solvents may be used in wet granulation?

A: Water, ethanol and 2-propanol

What happens to the wet mass during wet granulation?

It is pushed through a sieve to produce wet granules that require drying

What are the types of wet granulators listed in the notes?

Shear granulators, high-speed granulators and fluidised-bed granulators

What characterises dry granulation?

No liquid is used; pressure is generally applied

How are powder particles aggregated during dry granulation?

Under high pressure

What are the two dry granulation techniques mentioned?

Slugging (an older process) and roller compaction

When is dry granulation particularly useful?

For drugs sensitive to water

What are the five particle bonding mechanisms in granulation?

Adhesion and cohesion forces in liquid films;

interfacial forces in liquid films;

solid bridges after solvent evaporation;

attraction forces;

mechanical interlocking

What are the stages of the granulation mechanism?

Nucleation → transition → ball growth

How do granules compare with oral powders?

They are similar but have a larger particle size

What is the main benefit of granules regarding ingredient distribution?

They prevent ingredient segregation

What categories of granules are listed in the notes?

Effervescent granules, coated granules, modified-release (MR) granules and gastro-resistant (GR) granules

Which drugs are most suitable for granule dosage forms?

Low-toxicity, high-dose drugs

What disadvantages do granules share with oral powders?

Many of the disadvantages of oral powders

What is total moisture content?

The total amount of liquid associated with a wet solid

What is unbound water in a wet solid?

Water that exists as a liquid and exerts its full vapour pressure

How is unbound water removed during drying?

By evaporation; it is readily lost

What is free moisture content?

The amount of unbound water that is easily lost

What is equilibrium water content?

The moisture content of water that is difficult to removE

What factors must be considered when selecting a drying process?

Heat sensitivity, physical characteristics of materials, nature of the liquid, scale, sterility/aseptic manufacture and sources of heat

Which drying method uses convection to dry wet solids?

Convective drying using a fluidised-bed dryer.

Which drying method uses conduction to dry wet solids?

Conductive drying using a vacuum oven

How does radiation drying work according to the notes?

Through radiation heat transmission

Which drying method is used for solutions and suspensions?

Spray drying

What is freeze drying also called?

Lyophilisation

What must be considered when formulating a tablet?

Correct dose, acceptable appearance, controlled and reproducible drug release, biocompatibility, mechanical strength, chemical/physical/microbiological stability and safe packaging

What aspects of tablet appearance matter to end users?

Weight, colour and other appearance characteristics.

What is the purpose of a filler (diluent) in a tablet?

To provide suitable tablet size and handling characteristics

What minimum tablet weight is usually considered suitable for handling?

At least 50 mg

What characteristics should an ideal filler have?

Inert, non-hygroscopic, biocompatible, good biopharmaceutical and technical properties, acceptable taste and low cost

examples of fillers ?

Lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, cellulose and dicalcium phosphate dihydrate

What is the purpose of a tablet disintegrant?

To ensure the tablet breaks down in liquid, increasing the dissolution rate

How do disintegrants help tablets break down?

By facilitating water uptake and rupture of the tablet

What are examples of tablet disintegrants?

Starch, cellulose, cross-linked PVP, sodium starch glycolate and sodium carboxymethylcellulose

What starch concentration is stated for disintegrants?

Less than 10%.

Why may dissolution enhancers be needed?

For drugs with low aqueous solubility

How can salts help dissolution?

They can increase dissolution rate

How do surfactants enhance dissolution?

Improve wetting and increase surface area.

What are two examples of surfactants used as dissolution enhancers?

Sodium lauryl sulphate and polysorbates

What is the purpose of a tablet binder?

To form granules with suitable properties

What are three ways to add a binder?

Dry powder before wet granulation, solution during wet granulation, or dry powder before compaction

What binder concentration is stated in your notes?

2–10% by weight

Which type of binder is generally most effective?

Solution binders

What are examples of binders ?

Gelatin, PVP, PEG, sucrose, cellulose, methylcellulose, cellulose derivatives and starch

What is the purpose of a glidant?

To improve powder flow

Examples of glidants and concentrations?

Silica (less than 0.2%), magnesium “storage” (less than 1%) and talc (1–2%)

What is the purpose of a tablet lubricant?

To reduce friction during tablet ejection

What happens during fluid lubrication?

A fluid layer separates moving surfaces to reduce friction

How common is fluid lubrication in tablet manufacture?

It is rarely used

What is boundary lubrication?

Reduced friction due to interactions between sliding surfaces

What is one possible disadvantage of tablet lubricants?

They may reduce tablet strength

examples of lubricants

Magnesium stearate”, stearic acid, PEG, sodium lauryl sulphate, sodium stearyl fumarate and liquid paraffin

What is the purpose of an antiadherent?

To prevent powder sticking to punch faces

What are sticking and picking in tabletting?

Powder adhering to punches and forming a layer on them

: How can powder adhering to punches affect tablets?

It can affect tablet uniformity

What are examples of antiadherents?

Magnesium stearate, talc, starch and cellulose

What is sorbent

Forms fluids whilst dry and helps incorporate oils into powders

examples of sorbent

Microcrystalline cellulose and silica

Why are flavouring agents added to tablets? A:

improve palatability

What is an important consideration when selecting tablet flavouring agents?

They are often heat-sensitive

Why are colourants added to tablets?

For identification and patient adherence

When can colourants be added during tablet manufacture?

During coating or before compaction

What is the physical form of colourants described in your notes?

Insoluble powder

How are colourants incorporated during granulation?

They are dissolved during granulation

What can cause colour variation during tablet manufacture?

Drying

What is the difference between dyes and pigments in film coating?

Dyes are water-soluble; pigments are water-insoluble

What are examples of tablet colourants?

Iron oxide pigments, titanium dioxide and aluminium lakes

What happens during the die-filling stage of tabletting?

Powder flows from the hopper into a die closed by the lower punch

What happens during tablet formation?

The upper punch descends and compresses powder between the punches, then ascends

What happens during tablet ejection?

The lower punch ascends to allow tablet removal

What are the three main types of tablet press?


: Single punch, rotary, computerised

What does a single punch press contain?


One die and one pair of punches

What is the output of a single punch press?

~200 tablets/min

What is a single punch press mainly used for?


Small batches only

What is the output of a rotary press?


>10,000 tablets/min - increased tablet output

How are dies and punches arranged in a rotary press?


In a continuous circle - punches controlled

What is a computerised tablet press useful for?


Developmental processes

What are the main technical problems in tablet manufacture?


Weight/dose variation,

mechanical strength,

capping/lamination,

adhesion to punches,

high ejection friction

Why is granulation used to increase bulk density?


To fill the die appropriately

How does granulation reduce weight variation?


Improved flow

How does granulation improve powder uniformity?


Improves homogeneity and reduces segregation -makes sure equal distribution of API through tablet

How can granulation improve compatibility?


Adding binder

How can granulation optimise dissolution of poorly soluble particles?


Mix with hydrophilic filler, binder or surfactant