Solid Drug Delivery

Systems (Part 2)

By Ms. N. Akombaetwa Maliande

Solid dosage forms
• Drug substances are most frequently administered as solid dosage
formulations (≈90%), mainly by the oral route
• Tablets and capsules are the most frequently used solid dosage forms,
they are unit dosage forms,
• They comprise a mixture of ingredients presented in a single rigid
entity, usually containing an accurate dose of a drug
• Solid dose formulations must have the desired release properties
coupled with manufacturability and aesthetics and must involve
rational formulation design
Solid dosage forms: Tablets
• (1) conventional compressed tablets;
• (2) multiple compressed tablets;
• (3) enteric-coated tablets;
• (4) sugar-coated tablets;
• (5) film-coated tablets;
• (6) chewable tablets;
• (7) effervescent tablets;
• (8) buccal and sublingual tablets;
• (9) vaginal tablets;
• (10) Chewing gums;
• (11) Orally disintegrating tablets; and
• (12) Medicated lozenges
Solid dosage forms: Tablets
Conventional compressed tablets
• Are designed to rapidly disintegrate and quickly release the drug
release. Are a common type, manufactured by compression of
granules or powders into the required geometry
Multiple compressed tablets
• These are composed of at least two layers either multiple-layered or
compression coated
• Done to separate incompatible drugs, deliver API at different rates
and sites or coat the drug
Solid dosage forms: Tablets
Enteric-coated tablets
• These tablets are coated with a polymer that dissolves in pH>5. E.g.
cellulose actetate phthalate/cellulose acetate butyrate,
hydroxypropylmethyl cellulose succinate and methacrylic acid co-
polymers (Eudragit)
Sugar-coated tablets
• These are coated with a concentrated sugar solution to improve the
appearance or mask bitter taste.
• Give tablets a glossy elegant look
Solid dosage forms: Tablets
Film-coated tablets
• These are coated with a polymer or a mixture of polymers, have better
mechanical properties than sugar coat.
• Are soluble (hydroxypropylmethylcelluose, hydroxypropylcellulose,
Eudragit E100) or insoluble (ethylcellulose and Eudragit RS and RL)
• Film coats control the rate and duration or target of drug release
Chewable tablets
• Are chewed within the buccal cavity prior to swallowing. Mainly
designed for people with swallowing difficulty or anti-acid formulations
Solid dosage forms: Tablets
Effervescent tablets
• These rapidly disintegrate when added to an aqueous solutions. The
disintegration results from a chemical interaction between an organic
acid (e.g. citric acid) and sodium bicarbonate in the presence of water
that produces carbon dioxide
Buccal and sublingual tablets
• these are held within the oral cavity and slowly dissolve; the drug is
absorbed across the buccal mucosa to produce rapid systemic effect.
• should not contain components that stimulate the production of saliva
• E.g. nifedipine, glyceryl trinitrate
Solid dosage forms: Tablets
Vaginal tablets
• These are ovoid-shaped inserted into the vagina, with slow
dissolution (not disintegration) releasing the API to provide local
effect
Chewing gums
• Medicated chewing gums are made with a tasteless masticatory gum
base that consists of natural or synthetic elastomers.
• Excipients include fillers, softeners, and sweetening and flavoring
agents. E.g. nicotine gum
Solid dosage forms: Tablets
Orally disintegrating tablets
• These are dissolve/disintegrate rapidly in the saliva, within seconds or minutes, do not
require water and are ideal for people with swallowing difficulty
• Are generally prepared using freeze drying, compaction, or molding methods E.g.
Benadryl fastmelt and Zofran
Lozenges
• these dissolve/disintegrate slowly in the mouth to release drug into the saliva, They
usually contain one or more ingredient in a sweetened flavored base for local deliver
such as anesthetics, antiseptics and antimicrobials.
• Traditional drugs used in this dosage form include phenol, sodium phenolate,
benzocaine, cetylpyridinium chloride, mucin, decongestants and antitussives
• The choice of binder, filler, color, and flavor is particular important.
Solid dosage forms: Tablets
Excipients
• Diluents/fillers: increase the mass of the tablets that contain a low
concentration of therapeutic agent. E.g. lactose, starch, dibasic
calcium phosphate, microcrystalline cellulose (MCC) and mannitol
• Binders: Are predominantly polymeric components that are used in
the production of tablets by the wet granulation method. E.g acacia,
hydroxypropylmethylcellulose, polyvinylpyrrollidone, sucrose, MCC,
hydroxypropylcellulose
Solid dosage forms: Tablets
Excipients
• Disintegrants: facilitate the breakdown of the tablet into granules. Act
by increasing porosity or wettability (starch, MCC, sodium starch
glycolate- SSG), swelling (SSG, croscarmellose sodium, crospovidone,
pregelatinised starch) or gas production
• Lubricants: reduce friction between die/tablet press and tablet
surface. Are either insoluble (Magnesium stearate, Stearic acid,
Glyceryl behenate, Glyceryl palmitostearate) or soluble (Polyethylene
glycol (PEG), Polyoxyethylene stearates, Lauryl sulphate salts)
Solid dosage forms: Tablets
Excipients
• Glidants: Enhance the flow properties of the powders within the
hopper and into the tablet die in the tablet press. They need to be
small and arranged at the surface of the particles/granules. Glidants
are typically hydrophobic e.g. talc and colloidal silicon dioxide
• Adsorbents: Are used whenever it is required to include a liquid or
semisolid component within the tablet formulation e.g. magnesium
oxide/carbonate and kaolin/bentonite
Solid dosage forms: Tablets
Excipients
• Sweetening agents/flavors: Added to control the taste and improve
acceptability of tablets. E.g sucrose, liquid glucose, glycerol, sorbitol,
saccharin sodium and aspartame; flavors mask salty, sweet, bitter and
sour (vanilla, mint, citrus, menthol)
• Colours: Generally formulated either to improve the appearance or
to identify the finished product uniquely
• Surface-active agents: May be incorporated into tablets to improve
the wetting properties of hydrophobic tablets and hence increase the
rate of tablet disintegration. E.g. sodium lauryl sulphate
Solid dosage forms: Tablets
Solid dosage forms: Capsules
• Capsules are solid-dosage forms that are most commonly composed of
gelatin shell that contains a drug-containing formulation
• There are hard and soft gelatin capsules these differ in both mechanical
properties and design
• Hard gelatin capsules are less flexible and comprise a capsule and body,
while soft gelatin capsules are more flexible and comprise a one piece shell
• Hard gelatin capsules may be filled with powders, tablets, semisolids and
non-aqueous liquids/gels.
• Soft gelatin capsules are usually filled with non-aqueous liquids containing
the therapeutic agent either dispersed or dissolved within this carrier
Solid dosage forms: Capsules
Solid dosage forms: Capsules
• Capsules are primarily (but not exclusively) manufactured using
gelatin
• Gelatin is a mixture of proteins extracted from animal collagen by
either partial acid or partial alkaline hydrolysis
• The isoelectric points differs based on extracting solvent resulting in
differing solubilities as a function of pH
• Gelatin is non-toxic, soluble in biologic fluids at room temperature,
and has excellent mechanical and rheological properties that change
with changes in temperature
Solid dosage forms: Capsules
• Excipients added to gelatin solution prior to filling include colorants
and Wetting agents/lubricants
• Characteristics of powder fills for capsules are similar to those
required for tablets
• Liquid/semi solid fills maybe Lipophilic or water miscible containing
dissolved or dispersed therapeutic agent
• Surface-active agents and Viscosity-modifying agents are added to the
fluid fill of hard gelatin capsules to enhance stability
• Plasticizers (mostly glycerol or sorbitol) are added to gelatin to make it
more flexible and produce soft gelatin capsules
Solid dosage forms: Dry powders
• Dry powder formulations have been recognized as efficient nasal
delivery systems offering numerous advantages
• Preservatives are not required, they are more stable and provide
prolonged contact with the mucosa.
• Powders used for nasal administration need optimized particle size
and morphology
• Otherwise they could potentially cause irritation in the nasal cavity
• Commonly used polymer carriers include starch, dextrans, polyacrylic
acid derivatives, cellulose derivatives- MCC, chitosan, sodium alginate,
hyaluronans, and polyanhydrides
Powders for inhalation
• Dry powder inhaler formulations consist usually of either a drug only
formulation or an ordered mixture of drug and excipient
• Drug particles size should be suitable (1 – 5 μ m)
• Traditionally, micronization or jet - milling methods are used in
processing
• Micronized powders possess high intramolecular forces and are
cohesive
• Cohesion is overcome by incorporating a carrier excipient
• Lactose monohydrate is used most often; it is inert, cheap, widely
available, and GRAS (generally regarded as safe) non - toxic
Powders for inhalation
• Shape and surface properties of the drug and/or carrier particles are
critical in controlling the dose of drug that is delivered.
• they should not be too smooth or too rough, sometimes micronized
carrier particles are included to improve drug release
References
• 1. Aulton M (2005), 7th Edition. Pharmaceutics, The Science of
Dosage Form Design, Churchill Livingstone Press. ISBN: 0-443-05550-
5.
• 2. Alexander TF (2011), 5th Edition. Physicochemical Principles of
Pharmacy, Pharmaceutical Press. ISBN-10-1-4200-6566-1.
• 3. Shayne CG (2008). Pharmaceutical Manufacturing Handbook,
John-Wiley & Sons. ISBN: 978-0-470-25958-0.
• 4. David Jones (2008). Fasttrack- pharmaceutics- dosage form and
design. Pharmaceutical press, London. ISBN 978 0 85369 764 0